Corexit EC9527A .
The following has been cited from various Wikipedia, Medipedia, MSDS , the ATSDR database., the Monsanto website, Valdezlink.com, the Pan Pesticides database, the OPD chemical buyer's directory, Hallstar, I make no claim to copyrights.
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Corexit EC9527A is 30-60% 2-Butoxyethanol by weight. 2-B ( I will use the abbreviation 2-B ) is a main ingredient in many fertilizers, pesticides, herbicides ( especially Roundup ), insecticides, fuels, fungicides, cosmetics & leather treatment , and oddly enough, it is commonly used for " handling " oil spills .
The main argument for the use of COREXIT products, I have heard , is based on the studies of algae and microbial life in the Gulf . This logic is blind to the consideration of the 4 crucial things. The proliferation rate of oleophillic microbial life ( The specific bacteria to the deep-water Gulf, Deltaproteobacteria, and the powerhouse shallow water oil eater Alcanivorax borkumensis ) when faced with an overabundance of food, the specific hydrocarbons they actually eat, the depth and temperatures at which they thrive, and how 2-B can kill them all before they get a chance to eat. People presenting these arguments also don't understand how the food chain works. Microbes secrete their own surfactant molecules to break up the oil before consuming the hydrocarbons. Other microbes don't make surfactants but devour oil already broken into small enough globs—including those broken down by Alcanivorax. These microbes cannot proliferate until the Oxygen is depleted from the water. The colder temp loving microbes eat only short-chain hydrocarbons like gases, and the warmer clime-preferring ones are easily killed by 2-B. In order for these cold temp loving microbes to digest Hydrocarbon gases, these gases must first be produced. The gases they actually do eat are methane (CH4 ) ethane (C2H6), propane (C3H8) and butane (C4H10). They gases they produce are Hydrogen Cyanide and Hydrogen Sulfide.
The breakdown products of COREXIT are CO2 and Carbon Monoxide, neither of which stay suspended in salt-water at 5k' +, nor do the indigenous bacteria in the Gulf eat them. What does stay suspended in water is 2-B.
So that argument is moot.
2-B has never been tested on any type of marine life for longer than 9 days, and the effects that are known, is that it's mutagenic , teragenic and carcinogenic. As far as the testing on humans or other mammals , there is plenty, it's all below. Of course if you don't care, then don't read it.
In the United States, the primary manufacturers of 2-B are : Eastman Chemical, Dow Chemical and Equistar. Monsanto and Dow AgroSciences LLC, a subsidiary of The Dow Chemical Company, are in partnership to develop GM crops. Monsanto sales of GM seeds in the US cover 90% of the market.There are also projects being undertaken by Makhteshim Agan, an Israeli bio-engineering firm purchased by Cibus Global .
2-B is the very same chemical used as an adjuvient in herbicides like Roundup. Most genetically modified crops like. Roundup-Ready Corn. as well as a majority of the cotton, oilseed and vegetable crops in the continental US. are engineered to resist Roundup. Monsanto also pushed for the passage of laws preventing farmers from saving their own seed without state regulations, thus forcing many to purchase Monsanto GM seedstock. The plants are also engineered to be sterile, forcing farmers to purchase expensive seedstock for every growing season. The official name for these seeds is the " Terminator ' series.
Throughout 2004 and 2005, Monsanto filed lawsuits against many farmers in Canada and the U.S. on the grounds of patent infringement, specifically the farmers' sale of seed containing Monsanto's patented genes. In some cases, farmers claimed the seed was unknowingly sown by wind carrying the seeds from neighboring crops, a claim rejected in Monsanto Canada Inc. v. Schmeiser. These instances began in the mid to late 1990s, with one of the most significant cases being decided in Monsanto's favor by the Canadian Supreme Court. By a 5-4 vote in late May 2004, that court ruled that "by cultivating a plant containing the patented gene and composed of the patented cells without license, the appellants (canola farmer Percy Schmeiser) deprived the respondents of the full enjoyment of the patent." With this ruling, the Canadian courts followed the U.S. Supreme Court in its decision on patent issues involving plants and genes.
This is a map showing which states have passed laws requiring farmers who produce their own seed to register their locations with the state and federal government. in the US state.
Here is the known registry status for 2-Butoxyethanol.
There are very disturbing implications this will have a devastating effect on any non-GM crops, indigenous plants or any other living organisms which happen to be located in the path of any weather systems that have picked up moisture from the Gulf of Mexico...... if this dispersant gets burned with oil....there will be gases like Hydrogen Cyanide, Hydrogen Sulfide ( Both chemical weapons constituents ) and Carbon Monoxide , as well as CO2 created. The effects could easily cascade through the food chain.
Let's first look at how it works, how it breaks down, and what the influencing factors are in the rate of breakdown.
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2-Butoxyethanol (bu-tox-zi-eth-an-ol) has many names, including ethylene glycol monobutyl ether, ethylene glycol butyl ether, ethylene glycol n-butyl ether, Butyl Cellosolve, butyl glycol, butyl Oxitol, glycol butyl ether, Dowanol EB, Gafcol EB, Poly-solv EB, and Ektasolve EB. Common abbreviations for 2-butoxyethanol include BE and EGBE.
In liquid form, it is an organic solvent with the formula BuOC2H4OH (Bu = CH3CH2CH2CH2). It is colorless, with a sweet, ether-like odour. It is a butyl ether of ethylene glycol. It is also a relatively nonvolatile, inexpensive solvent with modest surfactant properties. It makes a very attractive ingredient because of it's cost.
2-Butoxyethanol is a solvent in paints and surface coatings, as well as cleaning products and inks. Other products that contain 2-butoxyethanol include acrylic resin formulations, asphalt release agents, firefighting foam, leather protectors, oil spill dispersants, bowling pin and lane de-greaser, and photographic strip solutions. Other products containing 2-butoxyethanol as a primary ingredient include some whiteboard cleaners, liquid soaps, cosmetics, dry cleaning solutions, lacquers, varnishes, herbicides, and latex paints.
2-B damages the central nervous system causing all-the-time depression, memory loss, suicidal tenancies, even a change in personality, causing changes to hostile and aggressive behavior. It damages your skin, de-fatting it (It's used to treat and soften leather ) It damages the eyes (holes in retina) and causes endocrine disruption, as well as abnormal blood sugar, abnormal blood pressure, abnormal thyroid; searing headaches in the back of the head (pituitary?) and reproductive harm by damaging male testes and destroying the body's ability to produce sperm.
Moderate respiratory exposure to 2-butoxyethanol often results in irritation of mucous membranes of the eyes, nose and throat. Heavy exposure via respiratory, dermal or oral routes can lead to hypotension, metabolic acidosis, hemolysis, pulmonary edema and coma. Blood or urine concentrations of 2-butoxyethanol or its major toxic metabolite, 2-butoxyacetic acid, may be measured using chromatographic techniques to monitor worker exposure or to confirm a diagnosis of poisoning in hospitalized patients. A biological exposure index of 200 mg 2-butoxyacetic acid per g creatinine has been established in an end-of-shift urine specimen for exposed U.S. employees
2-Butoxyethanol usually decomposes in the environment within a few days and has not been identified as a major environmental contaminant. It is not known to bioaccumulate.
| Chemical Name: | 2-Butoxyethanol |
| CAS Number: | 111-76-2 |
| U.S. EPA PC Code: | 011501 |
| CA DPR Chem Code: | 1880 (Ethylene glycol, mono-butyl ether. Two chem codes for the same compound.) 89 (2-butoxyethanol. Two chem codes for the same compound.) |
| Molecular Weight: | 118.18 |
| Molecular Structure: |  |
| Use Type: |  Adjuvant , Fungicide , Microbiocide , Solvent |
| Chem Class: | Alcohol/Ether |
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2-Butoxyethanol is a common chelating agent.
Chelants, according to ASTM-A-380, are "chemicals that form soluble, complex molecules with certain metal ions, inactivating the ions so that they cannot normally react with other elements or ions to produce precipitates or scale."
Incidentally, Corexit is manufactured using sono-catalysis, the same technology I suggest to implicate in stopping the G.o.M. leak, under my topics, Capture and Tame the Oil Leak.
2-Buty. is completely soluble in water and in most organic solvents. This means that when it and water, or it and organic solvents are mixed, the mixtures form one layer, unlike mixing oil and water which separate into two layers. When bound with oil, it forms what's know as a " gassy cap " in the oil and chemical engineering industries. It keeps oil at a higher density, so it will float under the surface of the water and keep it together. It's effectiveness and the rate of, used in the application of managing oil leaks, is dependent on salt saturation levels and water temperatures. It is effective only to keep oil from the surface of the water. As a dispersant, according to the laws of chemistry, it wouldn't seem to be incredibly effective.
It's application in the formulation of fertilizer and herbicide/pesticide/insetcicides is as a adjuvient , which means that it is used to keep chemical formulas in liquid suspension.
How it " breaks down "
When a substance is released from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. This release does not always lead to exposure. You are exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance or by skin contact.
If you are exposed to 2-butoxyethanol or 2-butoxyethanol acetate, many factors determine whether you'll be harmed. These factors include the dose (how much), the duration (how long), and how you come in contact with it. You must also consider the other chemicals you're exposed to and your age, sex, diet, family traits, lifestyle, and state of health.
The vapor point is determined by the ambient air temperature and pressure . It will break down into CO2 and Carbon Monoxide rapidly at temperatures starting at 68 degrees F, but is persist when absorbed by living organisms. According to many independent studies, it is known to have many effects on physiological functionality of any living creature. The initial toxicity testing was done by the Exxon Corporation.
Breakdown of 2-B, courtesy of Health Canada
In air, 2-butoxyethanol is expected to exist almost entirely in the vapour phase, and reactions with photochemically produced hydroxyl radicals should be important. Tuazon et al. (1998) reported that the gas-phase reaction products of 2-butoxyethanol with hydroxyl radicals in the presence of nitric oxide were n-butyl formate, 2-hydroxyethyl formate, propanal, 3-hydroxybutyl formate, an organic nitrate and one or more hydroxycarbonyl products. Stemmler et al. (1997) irradiated synthetic air mixtures containing 2-butoxyethanol, methyl nitrite and nitric oxide in a Teflon bag reactor at room temperature. Themajor oxidation products were butyl formate, ethylene glycol monoformate, butoxyacetaldehyde, 3-hydroxybutyl formate and propionaldehyde, whereas minor products were 2-propyl-1,3-dioxolane, ethylene glycol monobutyrate, 2-hydroxybutyl formate, acetaldehyde, propyl nitrate and butyraldehyde. Physical removal of 2-butoxyethanol from air by precipitation and dilution in clouds may occur; however, its short atmospheric residence time indicates that wet deposition is of limited importance (Howard, 1993). Howard et al. (1991) estimated a half-life of 2-butoxyethanol in air of 3.28-32.8 hours, based on photooxidation.
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Howard et al. (1991) estimated that the unacclimated biodegradation half-life of 2-butoxyethanol in water would be 1-4 weeks under aerobic conditions. Because of its low log Kow and Henry's law constant, adsorption to particulates and volatilization from surface water are not expected to be important fate processes for 2-butoxyethanol (SIDS, 1996).
Because of its low organic carbon sorption coefficient (Koc = 67; Lyman et al., 1990), 2-butoxyethanol should be highly mobile in soil and potentially could reach groundwater if released into soil (SIDS, 1996). Howard et al. (1991) estimated a half-life of 2-butoxyethanol in groundwater would be 2-8 weeks, based on unacclimated aqueous aerobic biodegradation.
2.3.1.3 Soils
Howard et al. (1991) estimated that the half-life of 2-butoxyethanol in soil would be 1-4 weeks, based on unacclimated aqueous aerobic biodegradation.
2.3.1.4 Biota
A bioconcentration factor of 2.5 was calculated for 2-butoxyethanol (SRC, 1988). Bioaccumulation of 2-butoxyethanol in aquatic organisms would therefore not be significant.
2.3.1.5 Environmental distribution
A Level III fugacity model was used to estimate the environmental partitioning of 2-butoxyethanol when released into air, water or soil. Values for input parameters were as follows: molecular weight, 118 g/mol; vapour pressure, 296 Pa; water solubility, 63 500 mg/L; log Kow, 0.84; Henry's law constant, 0.551 Pa·m3/mol; half-life2 in air, 17 hours; half-life in water, 550 hours; half-life in soil, 550 hours; and half-life in sediment, 1700 hours. Modelling was based upon an assumed emission rate of 1000 kg per hour, although the emission rate used would not affect the estimated percent distribution. If 2-butoxyethanol were emitted into air, EQC (Equilibrium Criterion) Level III fugacity modelling predicts that about 66% would be present in air, about 20% in water and about 14% in soil. If 2-butoxyethanol were emitted into water, more than 99% would be present in water. If 2-butoxyethanol were released to soil, about 75% would be present in soil and about 25% in water.
2.3.2 Environmental concentrations
Few data on levels of 2-butoxyethanol in the environment have been identified for Canada or elsewhere. One study was conducted to determine concentrations of 2-butoxyethanol in multiple media to which humans are exposed in Canada, including drinking water and indoor and outdoor air (Conor Pacific Environmental Technologies Inc., 1998), as outlined below in Section 2.3.2.1. Additional data on levels of 2-butoxyethanol in specific media are presented in the subsequent sections.
2.3.2.1 Multimedia exposure study
2-Butoxyethanol was among the target volatile organic compounds (VOCs) in the second phase of a Health Canada-sponsored multimedia exposure study, which was conducted during 1997 (Conor Pacific Environmental Technologies Inc., 1998). However, analytical compromises to simultaneously determine low concentrations of numerous, diverse VOCs in various sample types adversely impacted the quality of the data obtained for 2-butoxyethanol. Consequently, confidence in the results of this study is low, due to limitations of the analytical methods involved, as discussed in Section 3.3.5.
Exposure to the target VOCs was measured for 50 participants from three different geographical areas across Canada. Thirty-five participants were randomly selected from the Greater Toronto area in Ontario, six from Queens Subdivision in Nova Scotia and nine from Edmonton, Alberta. For each participant, samples of drinking water, and beverages and indoor, outdoor and personal air were collected over a single 24-hour period. Samples of foods were not analysed for 2-butoxyethanol (Conor Pacific Environmental Technologies Inc., 1998).
The limit of detection for 2-butoxyethanol in samples of air collected for 24-hour periods with passive sampling devices was 0.84 µg/m3. Although confidence in the individual measurements is low due to high and variable blanks and low extraction recovery, the arithmetic mean concentrations3 of 2-butoxyethanol in outdoor, indoor and personal air samples were 8.4, 27.5 and 31 µg/m3, respectively, with maxima of 243, 438 and 275 µg/m3, respectively. Although confidence in quantitation for individual determinations is low, the quality of data is sufficient to confirm that levels in indoor air are greater than those in ambient air, based on consideration of arithmetic mean concentrations (i.e., 27.5 µg/m3 in indoor air versus 8.4 µg/m3 in outdoor air).
2-Butoxyethanol was detected in 68% of the 50 drinking water samples (detection limit 0.02 µg/L). Concentrations ranged from below the limit of detection to 0.94 µg/L, with a mean concentration of 0.21 µg/L. Duplicate portions of beverages consumed were collected and combined to provide a single composite beverage sample for each study participant. 2-Butoxyethanol was detected in 56% of the 50 beverage samples (detection limit 6.80 µg/L). Concentrations ranged up to 73.8 µg/L, and the mean concentration was 6.46 µg/L. As only composite samples were analysed, no information is available with regard to the type(s) of beverage(s) that contained detectable concentrations of 2-butoxyethanol.
2.3.2.2 Ambient air
In the Windsor Air Quality Study, the concentrations of 2-butoxyethanol in 24 samples of ambient air collected in the vicinity of an automotive plant and in 7 samples collected in downtown Windsor were measured. Concentrations of 2-butoxyethanol were less than the limit of detection (3.3 µg/m3) in all the samples collected in downtown Windsor. Of the 24 samples collected at the automotive plant, concentrations of 2-butoxyethanol were above the limits of detection (which ranged from 0.65 to 1.3 µg/m3) in 16 (67%); the mean value for these samples was 2.3 µg/m3, when concentrations in samples where 2-butoxyethanol was not detected were assumed to be equivalent to one-half the limit of detection, and the maximum concentration was 7.3 µg/m3. The authors stated that the probable source of 2-butoxyethanol in ambient air samples downwind of the plant was from paints and lacquers in which 2-butoxyethanol is used as a solvent (OMEE, 1994).
Similar levels were reported in outdoor air in other countries. In samples of ambient air collected between 1990 and 1993 in countries other than Canada, concentrations of 2-butoxyethanol ranged from below the limits of detection to 21 ppb (101 µg/m3) (Ciccioli et al., 1993, 1996; Daisey et al., 1994; Brinke, 1995; Shields et al., 1996). 2-Butoxyethanol has also been quantified in air from Terra Nova Bay, Antarctica, at concentrations ranging from 1.3 to 15 µg/m3 (Ciccioli et al., 1996).
2.3.2.3 Indoor air
Available data on concentrations of 2-butoxyethanol in residential indoor air, other than those for the multimedia investigation described in Section 2.3.2.1, are limited to detection of 2-butoxyethanol at a concentration of 8 µg/m3 in one of six samples of indoor air collected over 4-to 7-day periods in 1983-1984 from homes in northern Italy (De Bortoli et al., 1986). Concentrations of 2-butoxyethanol in the other five samples were below the limit of detection, which was not specified.
2-Butoxyethanol was measured in indoor air samples (three per site) at concentrations up to 33 µg/m3 during March and April 1991 at 70 office buildings in 25 states plus the District of Columbia across the United States (Shields et al., 1996). A specific limit of detection was not reported for 2-butoxyethanol; however, a general limit of detection of 0.5 µg/m3 was reported for VOCs. Geometric mean concentrations calculated based on the assumption of half of this general limit of detection (0.25 µg/m3) for samples in which the concentration of 2-butoxyethanol was below the limit of detection are reported for three categories of building. 2-Butoxyethanol was detected in 24% of the samples from 50 telecommunications offices at concentrations up to 33 µg/m3; the geometric mean concentration was 0.1 µg/m3. The compound was detected in 44% of the samples from nine data centres at concentrations up to 16 µg/m3, with a geometric mean concentration of 0.2 µg/m3. 2-Butoxyethanol was also detected in 73% of the samples from 11 administrative offices at concentrations up to 32 µg/m3, with a geometric mean concentration of 1.0 µg/m3 (Shields et al., 1996). In contrast, detectable concentrations of 2-butoxyethanol were not present in 70 samples of outdoor air collected in the immediate vicinities of these office buildings.
Indoor air was sampled between June and September 1990 in 12 office buildings in the San Francisco Bay area of northern California. Concentrations of 2-butoxyethanol ranged from below the limit of detection (0.4 ppb or 1.9 µg/m3) to 27 ppb (130 µg/m3). An arithmetic mean concentration was not reported. The geometric mean concentration was 1.6 ppb (7.7 µg/m3) in indoor air, compared with 0.39 ppb (1.9 µg/m3) in the air outside these buildings (Daisey et al., 1994; Brinke, 1995). However, the number of samples collected at each location, the frequencies of detection in indoor air and key details of the sampling and analytical methods were not reported.
2.3.2.4 Surface water
Water samples taken from a polluted river in Japan in 1980 contained 2-butoxyethanol at a concentration of 1.31-5.68 mg/L (Yasuhara et al., 1981).
2.3.2.5 Groundwater
No data were identified on the concentration of 2-butoxyethanol in groundwater in Canada or elsewhere.
2.3.2.6 Drinking water
In 29 samples of drinking water collected between 1989 and 1995 from four sites in Ontario, concentrations of 2-butoxyethanol were above the limit of detection (not specified) in one sample from each site (i.e., in 9-17% of total samples at each site). The highest concentration (5.0 µg/L) was measured in a sample collected in Port Dover (OMEE, 1996).
2.3.2.7 Soil
No data were identified on the concentration of 2-butoxyethanol in soil in Canada or elsewhere.
2.3.2.8 Food
Data on the levels of 2-butoxyethanol in food were not identified; however, 2-butoxyethanol was detected but not quantified in a sample of paper and paperboard food packaging materials in the United Kingdom (Castle et al., 1997).
2.3.2.9 Consumer products
2-Butoxyethanol is used as a solvent in a number of consumer products, including paints, paint thinners and cleaning products. In Canada, there are no regulations concerning permissible levels of glycol ethers, including 2-butoxyethanol, in consumer products (Health Canada, 1998a). Material Safety Data Sheets list the percent contents of 2-butoxyethanol as up to 5% in latex paints and up to 30% in paint thinners (General Paint Ltd., 1997). Of the cosmetic products currently registered for sale in Canada, 2-butoxyethanol is a registered component in 63 products, including hair dyes, manicure preparations (nail polishes and nail polish removers) and skin cleansers. Most of these products were reported to contain 2-butoxyethanol concentrations in the range of 3-10%, with one cleanser containing 1-3% and two nail polishes containing 0.1% or less (Health Canada Cosmetic Notification System, 2001). (The Food and Drugs Act stipulates that manufacturers and importers of new cosmetic products are required to notify Health Canada concerning the ingredients.) 2-Butoxyethanol is present in approximately 73 pesticides currently registered for use in Canada (see Section 2.2.1).
Concentrations of 2-butoxyethanol of up to 20% were reported in various cleaning products, including degreasers, polishes and windshield washer fluid, used in the United States (Flick, 1986, 1989). "Low-pollutant" paints contained up to 6% 2-butoxyethanol in a study conducted in Germany (Plehn, 1990). Industrial window cleaners used in France were reported to contain 0.9-21.2% 2-butoxyethanol (Vincent et al., 1993). In Australia, 434 cleaning products were reported to contain 2-butoxyethanol in 1994, at concentrations ranging from <1 to 94% (two-thirds of these contained less than 10%); many of these products were intended for industrial use or use in diluted form (National Industrial Chemicals Notification and Assessment Scheme, 1996).
Emissions of 2-butoxyethanol from 13 consumer products purchased in the Ottawa, Ontario, area were recently investigated by Health Canada (Cao, 1999; Zhu et al., 2001). Products selected were those that were believed most likely to contain 2-butoxyethanol, on the basis of other data presented here. 2-Butoxyethanol was detected in emissions from seven products, including cleaners, nail polish remover and hair colorant, at rates of up to 938 mg/m2 per hour. Analyses of the products indicated that the cleaners contained 0.5-3.7% 2-butoxyethanol, while the nail polish remover and hair colorant contained 3.8% and 25%, respectively.
2.4.1.1 Terrestrial organisms
No information on the effects of 2-butoxyethanol on wildlife was identified. Based on the results of inhalation studies presented in Section 2.4.3, the species that were most sensitive to airborne 2-butoxyethanol were rats and mice. In subchronic toxicity tests, alterations in hematological parameters indicative of hemolytic anemia were observed in female rats and mice at the lowest concentration tested, 31 ppm (150 mg/m3) (NTP, 1998). Hemolytic anemia was also noted in rats exposed to 31.2 ppm (151 mg/m3) 2-butoxyethanol in a 2-year bioassay (NTP, 1998).
2.4.1.2 Aquatic organisms
Chronic toxicity data have been identified for protozoans, algae and fish. The most sensitive organism was the blue-green alga,Microcystis aeruginosa, with an 8-day toxicity threshold of 35 mg/L for inhibition of growth (Bringmann and Kuehn, 1978). Acute toxicity data have been reported for protozoans, invertebrates and fish. The most sensitive organisms were the grass shrimp (Palaemonetes pugio), with a 96-hour LC50 of 5.4 mg/L (Biospherics Inc., 1981a), and the mummichog (Fundulus heteroclitus), with a 96-hour LC50 of 6.7 mg/L (Biospherics Inc., 1981b). These values are much lower than reported values for other organisms. The next most sensitive invertebrate was the oyster (species not stated), with a 96-hour LC50 of 89 mg/L (U.S. EPA, 1984). The most sensitive fish species was the bluegill (Lepomis macrochirus), with a 96-hour LC50 of 127 mg/L (CIBA-GEIGY Corp., 1979), although other authors reported much higher values for this species, as presented in Table 11 of Environment Canada (1999).
2.4.2 Abiotic atmospheric effects
Worst-case calculations were made to determine if 2-butoxyethanol has the potential to contribute to depletion of stratospheric ozone, ground-level ozone formation or climate change (Bunce, 1996).
The Ozone Depletion Potential (ODP) is 0, as 2-butoxyethanol is not a halogenated compound.
The Photochemical Ozone Creation Potential (POCP) was estimated to be 70 (relative to the reference compound ethene, which has a POCP of 100), based on the following formula:
POCP = (k2-butoxyethanol / kethene) x (Methene / M2-butoxyethanol) x 100
where:
* k2-butoxyethanol is the rate constant for the reaction
of 2-butoxyethanol with OH radicals (2.5 x 10 -1 cm3/mol per second),
* kethene is the rate constant for the reaction of
ethene with OH radicals (8.5 x 10-12 cm3/mol per second),
* Methene is the molecular weight of ethene
(28.1 g/mol), and
* M2-butoxyethanol is the molecular weight of
2-butoxyethanol (118 g/mol).
The Global Warming Potential (GWP) was calculated to be 3.1 x 10-5 (relative to the reference compound CFC-11, which has a GWP of 1), based on the following formula:
GWP = (t2-butoxyethanol / tCFC-11) x (MCFC-11 / M2-butoxyethanol)
x (S2-butoxyethanol / SCFC-11)
where:
* t2-butoxyethanol is the lifetime of 2-butoxyethanol (0.0016 years),
* tCFC-11 is the lifetime of CFC-11 (60 years),
* MCFC-11 is the molecular weight of CFC-11 (137.5 g/mol),
* M2-butoxyethanol is the molecular weight of 2-butoxyethanol (118 g/mol),
* S2-butoxyethanol is the infrared absorption strength of 2-butoxyethanol (2389/cm2 per atmosphere, default), and
* SCFC-11 is the infrared absorption strength of CFC-11 (2389/cm2 per atmosphere).
These figures suggest that 2-butoxyethanol does not contribute to stratospheric ozone depletion, its potential contribution to climate change is negligible, and its potential contribution to ground-level ozone formation is moderate. The magnitude of these effects would depend on the concentrations of 2-butoxyethanol in the atmosphere, which are estimated to be very low in Canada. 2-Butoxyethanol's contribution to ozone formation is therefore considered negligible compared with those of other more abundant smog-forming substances, such as the reference compound, ethene (Bunce, 1996).
2.4.3 Experimental animals andin vitro
2.4.3.1 Kinetics and metabolism
2-Butoxyethanol is rapidly absorbed following oral, inhalation and dermal exposure. Once absorbed, it is rapidly and extensively distributed throughout the body and rapidly eliminated principally in the urine as metabolites and exhaled as carbon dioxide (thus, there is little potential for bioaccumulation). It is metabolized in the liver primarily via alcohol and aldehyde dehydrogenases to 2-butoxyacetaldehyde and 2-butoxyacetic acid (BAA, the principal and putatively active metabolite, representing up to 75% of the absorbed dose). BAA may be subsequently detoxified through conjugation (at least with glutamine in humans, but possibly not in rats) or metabolized to carbon dioxide.
Comparatively minor pathways of 2-butoxyethanol metabolism result in the formation of other urinary metabolites, including glucuronide and sulphate conjugates (at least in rats) and ethylene glycol.
Although data are limited, the acetate moiety of 2-butoxyethanol (2-butoxyethyl acetate) appears to be rapidly hydrolysed to 2-butoxyethanol via esterases in several tissues in the body (Johanson, 1988). For this reason, data on the toxicity of 2-butoxyethyl acetate have been included in this assessment.
2.4.3.2 Acute toxicity
Based on LD50s and LC50s, 2-butoxyethanol and its acetate are of low to moderate toxicity to experimental animals following acute exposure. Hematological effects, as well as effects on the liver, kidney, lung and spleen, some of which may be secondary to hematotoxicity, have been observed in animals acutely exposed to lower doses or concentrations. For example, alterations in hematological parameters characteristic of hemolytic anemia have been observed in rats administered single oral doses as low as 125 mg/kg-bw, while hemoglobinuria was noted in older rats following gavage administration of 32 mg/kg-bw (Ghanayem et al., 1987). Exposure to airborne concentrations of 62 ppm (299 mg/m3) for 4 hours resulted in increased osmotic fragility of erythrocytes (Carpenter et al., 1956), whereas dermal exposure to 260 mg/kg-bw for 6 hours induced hemolysis in rats (Bartnik et al., 1987). Ghanayem et al. (1992) and Sivarao and Mehendale (1995) demonstrated that younger blood cells were more resilient to 2-butoxyethanol-induced hemolysis than were older cells, as rats that had been bled several days prior to exposure to a single oral dose were less severely affected than non-bled rats.
2-Butoxyethanol and its acetate are considered to be mildly to severely irritating to the skin and eyes, with the severity increasing with duration of exposure (Carpenter and Smyth, 1946; Smyth et al., 1962; Truhaut et al., 1979; Union Carbide, 1980; Jacobs et al., 1989; Kennah et al., 1989; Rohm and Haas Co., 1989; Jacobs, 1992; Zissu, 1995).
2.4.3.3 Short-term toxicity
Hematological effects appear to be the most sensitive endpoint in experimental animals following short-term exposure to 2-butoxyethanol by inhalation, ingestion or dermal contact, with rats being more sensitive than mice or rabbits. Hematological changes characteristic of hemolysis (including reductions in the red blood cell count, hemoglobin levels and hematocrit values) have been reported by a number of investigators in rats exposed repeatedly to 2-butoxyethanol for 2-65 days (Grant et al., 1985; Krasavage, 1986; NTP, 1989; Dieter et al., 1990; Ghanayem et al., 1992). In most of those studies in which hematological parameters were measured, these changes were observed at all doses administered by gavage or in the drinking water (i.e.,≥100 mg/kg-bw per day); in only one study in rats exposed for only 3 days (which was designed primarily to investigate developmental toxicity) was a No-Observed-Effect Level (NOEL) of 30 mg/kg-bw per day determined (NTP, 1989). In several of these short-term studies in rats, the hematological changes appeared to be reversible after cessation of exposure (Grant et al., 1985; NTP, 1989; Ghanayem et al., 1992), while in other studies it appeared that tolerance or autoprotection developed in rats repeatedly exposed to 2-butoxyethanol, based on the lessening in severity of effects (Ghanayem et al., 1992; Sivarao and Mehendale, 1995). In general, mice appear to be less sensitive to 2-butoxyethanol-induced hematological effects than rats. At oral doses of 500 mg/kg-bw per day or more, the only effect observed on the blood in mice was a reduction in red blood cell count (Nagano et al., 1979, 1984).
Effects on other organs, including the spleen, liver and kidneys, have also been observed in rats exposed to 2-butoxyethanol, although generally only at doses or concentrations greater than those associated with alterations in hematological parameters. For example, in two studies, changes in relative weights were noted in rats administered oral doses of 100 mg/kg-bw per day or more for 3 days (NTP, 1989) or 125 mg/kg-bw per day for 12 days (Ghanayem et al., 1992); however, no effects on organ weights were observed in other short-term studies in rats administered higher doses for longer durations (Dieter et al., 1990; Exon et al., 1991; NTP, 1993). Similarly, increased weights of spleen and kidney were noted in rats exposed to 200 ppm (966 mg/m3) 2-butoxyethanol via inhalation (Tyl et al., 1984). In mice, decreased relative thymus weights were noted following administration of doses of 370 mg/kg-bw per day or more (NTP, 1993).
In inhalation studies, hematological changes were noted in rats exposed to 2-butoxyethanol for up to about 30 days at concentrations of 86 ppm (415 mg/m3) or more, but not at 50 ppm (242 mg/m3) or lower concentrations (Carpenter et al., 1956; Dodd et al., 1983; Tyl et al., 1984). A reversible increase in erythrocyte fragility was observed in mice exposed to 100 ppm (483 mg/m3) or higher concentrations, with transient hemoglobinuria being observed at 200 ppm (966 mg/m3) or more (Carpenter et al., 1956). Indications of hemoglobinuria were also observed in rabbits exposed to 200 ppm (966 mg/m3) 2-butoxyethanol or 400 ppm 2-butoxyethyl acetate (2616 mg/m3, equivalent to 1932 mg 2-butoxyethanol/m3) (Truhaut et al., 1979; Tyl et al., 1984). Alterations in blood parameters were also noted in limited earlier investigations in dogs and monkeys exposed via inhalation, but not in guinea pigs (Carpenter et al., 1956). Non-hematological effects observed in inhalation studies included an increase in weights of spleen and kidney in rats exposed to 200 ppm (966 mg/m3) 2-butoxyethanol (Tyl et al., 1984) and histopathological changes in the kidney in rabbits exposed to 400 ppm 2-butoxyethyl acetate (2616 mg/m3, equivalent to 1932 mg 2-butoxyethanol/m3) (Truhaut et al., 1979).
Alterations in blood parameters were also observed in an earlier investigation in rabbits repeatedly administered 180 mg 2-butoxyethanol/kg-bw per day or more by dermal contact (Union Carbide, 1980).
2.4.3.4 Subchronic toxicity4
2.4.3.4.1 Oral
In the only subchronic oral study in rats identified (NTP, 1993), regenerative hemolytic anemia, characterized by decreases in red blood cell count, hemoglobin concentration and hematocrit and increases in mean cell volume, mean cell hemoglobin and reticulocyte count, was observed following exposure to 2-butoxyethanol in the drinking water for 13 weeks. Female F344/N rats were more sensitive than males to 2-butoxyethanol-induced hematological effects, as alterations in most of these parameters were observed in all dose groups (i.e.,≥750 mg/L in drinking water, or ≥82 mg/kg-bw per day) in females and only in the higher dose groups (i.e.,≥1500 mg/L or ≥129 mg/kg-bw per day) in males. Relative weights of several organs were increased, with females again being more sensitive than males. Histopathological changes were observed in the liver, spleen, bone marrow and uterus, with effects (cytoplasmic alteration, possibly associated with enzyme induction) being observed in the liver at all doses in both sexes. The Lowest-Observed-Effect-Level (LOEL) for hematological and hepatic effects was considered to be 750 mg/L, or 69 and 82 mg/kg-bw per day in males and females, respectively.
Hematological parameters were not examined in the two identified subchronic oral studies in mice (Heindel et al., 1990; NTP, 1993). The most sensitive effect observed in B6C3F1 mice administered 2-butoxyethanol in the drinking water for 13 weeks was increased relative kidney weight in female mice at all exposure levels (i.e.,≥750 mg/L or ≥185 mg/kg-bw per day); there were no accompanying histopathological changes in the kidney (NTP, 1993). Altered organ weights (kidney and liver), along with decreased body weights, were also observed in CD-1 mice exposed to a concentration of 2-butoxyethanol in drinking water equivalent to a dose of 1300 mg/kg-bw per day for 15 weeks, although no histopathological changes were noted. These effects were not noted at the lower dose of 700 mg/kg-bw per day (Heindel et al., 1990).
2.4.3.4.2 Inhalation
Based on results of a subchronic inhalation study in F344/N rats exposed to up to 500 ppm (2415 mg/m3) for 14 weeks (NTP, 1998), there were changes in hematological parameters characteristic of macrocytic, normochromic, responsive anemia (i.e., increased mean cell volume, lack of change in mean cell hemoglobin values and increased reticulocyte count). Females were more sensitive than males, with alterations in hematological parameters observed at the lowest concentration tested (i.e., LOEL of 31 ppm [150 mg/m3]) in females, while the LOEL in males for these effects was 125 ppm (604 mg/m3); the NOEL in males was considered to be 62.5 ppm (302 mg/m3). The severity of these effects increased with concentration in both sexes, and there was no evidence of amelioration in response over time. In addition, in female rats at the higher concentrations, there was an increased incidence of thrombosis in the blood vessels of several tissues as well as bone infarction, which was hypothesized to have resulted from severe acute hemolysis or anoxic damage to endothelial cells, causing compromised blood flow. Other effects consistent with regenerative anemia observed in both male and female rats included excessive hematopoietic cell proliferation in the spleen, hemosiderin pigmentation in the hepatic Kupffer cells and renal cortical tubules and bone marrow hyperplasia. Inflammation and/or hyperplasia of the forestomach also occurred in rats of both sexes exposed to the higher concentrations (250 and 500 ppm [1208 and 2415 mg/m3]), while changes in relative kidney and liver weights were noted at 62.5 ppm (302 mg/m3) and above in females and 250 ppm (1208 mg/m3) and above in males.
Hematological effects, consisting of slight changes in red blood cell count, hemoglobin levels and mean corpuscular hemoglobin, were also observed in female Fischer 344 rats exposed to 77 ppm (372 mg/m3) for 6 weeks (Dodd et al., 1983); however, after 13 weeks of exposure, values for these parameters were generally similar to those of controls (contrary to the observations in this strain of rats by the NTP [1998]). Males appeared to be much less sensitive, as the only effect on blood was a very slight decrease in red blood cell count after 13 weeks at 77 ppm (372 mg/m3). No indication of hematotoxicity was observed at 25 ppm (121 mg/m3), which is considered to be the NOEL. No histopathological changes or alterations in clinical chemistry were noted in exposed rats (Dodd et al., 1983). Conversely, however, renal tubular nephritis was reported in Wistar rats (primarily in males) exposed to 100 ppm 2-butoxyethyl acetate (654 mg/m3, equivalent to 483 mg 2-butoxyethanol/m3) for 10 months, although there were no hematological effects (based on a limited range of parameters) (Truhaut et al., 1979).
Alterations in hematological parameters indicative of hemolytic anemia (hemoglobin, hematocrit and erythrocyte counts) were also the most sensitive endpoints observed in B6C3F1 mice exposed for 13 weeks (NTP, 1998). However, the anemia in mice was considered to be normocytic, normochromic and responsive (compared to the macrocytic anemia noted in rats), as 2-butoxyethanol did not induce any changes in mean cell volume. In addition, based on the magnitude of the changes, the anemia was less severe in mice than in rats, although females were again more sensitive than males (LOELs in females and males of 31 ppm [150 mg/m3] and 125 ppm [604 mg/m3], respectively). As in rats, effects consistent with regenerative anemia (hemosiderin pigmentation and increased hematopoiesis in the spleen) were also observed. The incidence of hyperplasia of the forestomach was increased in female mice exposed to 125 ppm (604 mg/m3) or more and in males at the highest concentration, 500 ppm (2415 mg/m3); various lesions also appeared in other tissues in females at 500 ppm (2415 mg/m3) (a concentration that was also associated with increased mortality in both sexes).
Increased osmotic fragility of erythrocytes, transient hemoglobinuria and reversible changes in liver weights were observed in C3H mice following exposure to concentrations of 2-butoxyethanol of 100 ppm (483 mg/m3) or more for up to 90 days; however, erythrocytes returned to normal between exposure episodes (Carpenter et al., 1956).
Similar to the results reported for rats in the same study, renal tubular nephritis was observed in rabbits exposed to 100 ppm 2-butoxyethyl acetate (654 mg/m3, equivalent to 483 mg 2-butoxyethanol/m3) for 10 months, although there were no effects on hematological or urinalysis parameters (Truhaut et al., 1979).
2.4.3.4.3 Dermal
No overt signs of toxicity and no effects on the weight or microscopic appearance of unspecified organs or on hematology (including osmotic fragility tests) were observed in rabbits administered daily dermal applications (covered) of up to 150 mg 2-butoxyethanol/kg-bw per day for 13 weeks (CMA, 1983).
2.4.3.5 Chronic toxicity and carcinogenicity 5
Results are available for bioassays in rats and mice exposed to 2-butoxyethanol for 6 hours per day, 5 days per week, for up to 2 years (NTP, 1998). Similar to the critical endpoints observed in shorter-term studies, chronic exposure to 31.2 ppm (151 mg/m3, the lowest concentration tested) 2-butoxyethanol or greater resulted in hemolytic anemia (characterized as macrocytic, normochromic anemia based on decreases in hematocrit, hemoglobin concentrations and erythrocyte counts, increases in mean cell volume and mean cell hemoglobin, and the lack of effect on mean cell hemoglobin concentration) in F344/N rats. Consistent with results observed in earlier studies and toxicokinetic data that indicate slower clearance of the active metabolite, BAA, and greater activity of the relevant isoenzyme in females (see Section 2.4.3.11), in general, the severity of hematological effects was greater in females than in males, with alterations in multiple parameters being observed at the lowest concentration tested (i.e., 31.2 ppm [151 mg/m3], considered to be the LOEL), while only mean cell volume was affected in males at this concentration. The severity of these effects increased with exposure level and the effects were persistent throughout the 12 months during which hematological parameters were monitored; there was no indication of amelioration over time in males, while in females, there were slight decreases in the magnitude of the changes in some parameters at 12 months. The anemia was considered to be responsive, based on the observation of increased reticulocyte and nucleated erythrocyte counts and a decrease in the myeloid to erythroid ratios.
There was a marginal increase in the incidence of pheochromocytomas (primarily benign, with one case of malignant tumour) of the adrenal gland in female rats at the highest concentration (125 ppm [604 mg/m3]), which, while not significantly elevated compared with concurrent controls, was greater than the incidence of this lesion observed in historical controls at the National Toxicology Program (NTP). There was also a non-statistically significant increase in the incidence of hyperplasia of the adrenal medulla of females at 125 ppm (604 mg/m3). No such increases were observed in males. Other exposure-related histopathological changes observed in rats included increased incidences of minimal hyaline degeneration of the olfactory epithelium (which was considered to be adaptive/protective rather than adverse), increased incidences of Kupffer cell pigmentation in the liver of both sexes at the two highest concentrations, and an increase in splenic fibrosis in males at 62.5 ppm (302 mg/m3) and above. Based on the results of this study, the NTP concluded that there was no evidence of carcinogenic activity in male F344/N rats and equivocal evidence of carcinogenic activity in female rats of this strain, since the slight increase in pheochromocytomas could not be attributed with certainty to exposure to 2-butoxyethanol.
Consistent with the results reported for shorter-term studies, B6C3F1 mice were less sensitive than rats to the hematological effects associated with exposure to 2-butoxyethanol. Anemia, characterized by decreases in hematocrit, hemoglobin concentrations and erythrocyte count, was present in mice exposed to the two higher concentrations (125 and 250 ppm [604 and 1208 mg/m3]), and there was some evidence of anemia in females at 62.5 ppm (302 mg/m3), but only at one time point. In general, based on the lack of consistent changes in mean cell volume and mean cell hemoglobin concentrations, the effects were consistent with normocytic, normochromic anemia. Although considered responsive, based on the increased reticulocyte counts, this response ameliorated over time. In addition, contrary to the observations in rats, there were no decreases in myeloid to erythroid ratios; in fact, there were increases in some exposed groups. Thrombocytosis was present in both sexes of mice at all concentrations, based on the increase in platelet counts, with time of appearance being inversely related to concentration. As in rats, females were more sensitive than males, with significant alterations in hematological parameters generally occurring earlier and at lower exposure levels in female mice.
Although mice were less sensitive than rats to the hematotoxicity of 2-butoxyethanol, several other non-neoplastic and neoplastic effects occurred at lower concentrations in mice than in rats following chronic exposure. There were increased incidences of papillomas or carcinomas (combined) of the forestomach in both sexes, which were statistically significant in females exposed to 250 ppm (1208 mg/m3) compared with concurrent and historical controls and in males at 125 and 250 ppm (604 and 1208 mg/m3) compared with historical controls (but not study controls). In addition, the incidence of hyperplasia of the epithelium of the forestomach was significantly increased in a concentration-related manner in all exposed groups, which was accompanied by a concentration-related trend in the incidence of ulcers of the forestomach in female mice. The severity of the epithelial hyperplasia in females also increased with exposure level, as mean severity scores in animals with lesions were 1.8, 2.0, 2.4 and 2.9 at 0, 62.5, 125 and 250 ppm (0, 302, 604 and 1208 mg/m3), respectively.
There was also a concentration-related increase in the incidence of hemangiosarcomas of the liver in male mice (significant at 250 ppm [1208 mg/m3]); hemangiosarcomas were also detected in the bone marrow of two mice exposed to 250 ppm (1208 mg/m3) (one of which also had a hemangiosarcoma in the spleen, while the other had a hemangiosarcoma in the heart) and in one mouse exposed to 62.5 ppm (302 mg/m3). A significant increase in the incidence of hepatocellular carcinomas was also observed in males at the highest concentration, although the incidence was within the range observed in historical controls. In addition, the incidences of hepatocellular adenomas were lower in exposed mice than in controls, and there was no indication of an association between exposure and induction of a related preneoplastic lesion. In spite of these facts, a potential role of 2-butoxyethanol in the development of malignant liver tumours could not be ruled out, and it was concluded that they may be exposure-related. Hemosiderin pigmentation of the Kupffer cells of minimal severity was also noted in the liver of exposed mice, which did not appear to be directly correlated to the incidence of neoplastic lesions in this organ.
Based on the increased incidence of hemangiosarcoma of the liver (males) and squamous cell papillomas or carcinomas of the forestomach (females), it was concluded that there was some evidence of carcinogenic activity of 2-butoxyethanol in male and female B6C3F1 mice, and the Lowest-Observed-Adverse-Effect Level (LOAEL) for non-neoplastic effects (hematotoxicity and forestomach lesions) was 62.5 ppm (302 mg/m3) in both sexes.
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2.4.3.6 Genotoxicity
The results of availablein vitro genotoxicity assays in mammalian cell lines have been somewhat mixed. Overall, there is equivocal evidence that 2-butoxyethanol may be very weakly genotoxicin vitro, as it was mutagenic at thehprt locus in Chinese hamster lung cells (Elias et al., 1996), but not at thehprt or gpt locus in Chinese hamster ovary cells (Union Carbide, 1989; Chiewchanwit and Au, 1995), and weakly positive or equivocal results were obtained for unscheduled DNA synthesis, micronuclei and mitotic division aberrations/aneuploidy (Union Carbide, 1989; Elias et al., 1996). Results for chromosomal aberrations were negative, while those for sister chromatid exchange were mixed (Union Carbide, 1989; Villalobos-Pietrini et al., 1989; NTP, 1993, 1998; Elias et al., 1996). 2-Butoxyethanol induced cell transformation at high concentrations and also inhibited intercellular communication (Welsch and Stedman, 1984; Kerckaert et al., 1996). However, it is important to note in interpretation of these data that exogenous metabolic activation was incorporated in few of these studies, particularly since the metabolites of 2-butoxyethanol, butoxyacetaldehyde and BAA, were genotoxic in mammalian cellsin vitro (Elias et al., 1996), with the intermediate butoxyacetaldehyde being significantly more active than the principal metabolite, BAA. Neither 2-butoxyethanol nor its metabolites induced mutations in prokaryotes (Kvelland, 1988; Zeiger et al., 1992; NTP, 1993, 1998; Hoflack et al., 1995; Gollapudi et al., 1996).
In the fewin vivo studies identified, 2-butoxyethanol did not induce micronuclei in the bone marrow of mice or rats administered up to 1000 mg/kg-bw via intraperitoneal injection (Elias et al., 1996; NTP, 1998) (which is significant in that the hematopoietic system has been demonstrated to be a target of 2-butoxyethanol-induced effects at much lower doses via ingestion and inhalation, some of which might be secondary to toxicity to circulating blood cells), nor were DNA adducts observed in several tissues examined in rats or transgenic mice exposed to 120 mg/kg-bw as a single oral dose or via repeated subcutaneous administration (Keith et al., 1996). Availablein vivo data for the metabolites are limited to a single study in which BAA also did not induce micronuclei in the bone marrow of mice (Elias et al., 1996).
2.4.3.7 Developmental and reproductive toxicity
In the available studies involving oral, inhalation or dermal exposure of Fischer 344 or Sprague-Dawley rats, CD-1 mice or New Zealand white rabbits, embryotoxic or fetotoxic effects or malformations have generally been observed only at or above doses that were also maternally toxic (Hardin et al., 1984; Schuler et al., 1984; Wier et al., 1987; NTP, 1989; Heindel et al., 1990). Hematological effects were reported in the fetuses of Fischer 344 rats exposed to 300 mg/kg-bw per day (which was also hematotoxic in the dams) (NTP, 1989), suggesting that the blood is also a sensitive target tissue in the developing young followingin utero exposure. Although a slight decrease in live pup weight was reported in CD-1 mice exposed to 700 mg/kg-bw per day in the drinking water, no statistically significant effects on pup weight were observed in the second generation exposed to the same dose (Heindel et al., 1990).
In the only study on the effects of exposure to 2-butoxyethanol on reproductive ability, fertility in female CD-1 mice (based on litter size and the proportion of live pups) was significantly reduced following administration of 1% 2-butoxyethanol or more in the drinking water (1300 mg/kg-bw per day), although these doses were also associated with high mortality (Heindel et al., 1990). (It has been hypothesized that fetal deaths may have been due to hydrops foetalis, associated with severe anemia induced by 2-butoxyethanol or its metabolite, BAA, transported across the placenta [Atkins, 1999]; however, no description of the possible cause of fetal death was presented in the report of this study.) Effects on male and female reproductive organs (including reduced weight or histopathological changes in the epididymis or testes, decreased sperm concentration, altered sperm morphology or uterine atrophy) were noted in F344 rats and B6C3F1 mice exposed to 2-butoxyethanol in the subchronic studies conducted by the NTP (1993, 1998), although some of these effects were not considered to be of biological significance and occurred only at doses or concentrations that also induced hematological and other effects. No effects on the testes were observed in acute or short-term studies (Nagano et al., 1979, 1984; Doe, 1984; Grant et al., 1985; Krasavage, 1986; Exon et al., 1991).
2.4.3.8 Immunotoxicity
Based on the limited available data, 2-butoxyethanol appears to have some immunomodulating potential, with mice being more sensitive than rats. Significant effects on indicators of immune function were observed in BALB/c mice administered repeated oral doses of 50 mg/kg-bw per day or more (Morris et al., 1996), while only slight or no changes in immune function parameters were noted in Fischer 344 and Sprague-Dawley rats administered higher doses (Exon et al., 1991; Smialowicz et al., 1992). Repeated dermal application of 1500 mg 2-butoxyethanol/kg-bw per day also resulted in reduced immune response in BALB/c mice (Singh et al., 1998); no similar studies in rats were identified. Reduced weights or histopathological changes were observed in the thymus or spleen of both mice and rats exposed subchronically or chronically to 2-butoxyethanol; however, these effects were considered likely to be secondary to hemolysis and decreased body weight (NTP, 1993, 1998).
2.4.3.9 Neurotoxicity
No investigations of the neurological effects of 2-butoxyethanol have been identified, although various signs of effects on the central nervous system, including loss of coordination, sluggishness, narcosis, muscular flaccidity and ataxia, have been reported at high doses or concentrations in numerous short-term studies (Carpenter et al., 1956; Dodd et al., 1983; Hardin et al., 1984; Krasavage, 1986).
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2.4.3.10 Investigations of hemolysis inin vitro systems
Differences in species sensitivity to hemolysis induced by 2-butoxyethanol and its metabolites have been investigated in severalin vitro studies. Consistent with thein vivo studies discussed above, BAA was more potent than either the parent compound or the acetaldehyde metabolite (Bartnik et al., 1987; Ghanayem, 1989; Sivarao and Mehendale, 1995). Although slight species differences were observed in erythrocytes exposed to 2-butoxyethanol (with humans being less sensitive than rats, mice, dogs and guinea pigs) (Carpenter et al., 1956; Bartnik et al., 1987), variability between species was much more pronounced when cells were exposed to BAA (Bartnik et al., 1987; Ghanayem and Sullivan, 1993; Udden and Patton, 1994), with erythrocytes from humans being less sensitive than those from rats, as well as those from mice and other species.
In Bartnik et al. (1987), hemolysis in blood from four adult male Wistar rats and human erythrocytes isolated from the blood of healthy adult male donors (no further details provided) was examinedin vitro. The lowest concentration of BAA administered (1.25 mM) resulted in 25% hemolysis of rat erythrocytes after 180 minutes. In contrast, 15 mM BAA did not produce measurable hemolysis in human erythrocytes over the same time. In consequence, these data suggest that rat erythrocytes are at least 12 times more sensitive than the human erythrocytes. This study was conducted in washed erythrocytes rather than whole blood, indicating that the species difference in sensitivityin vitro must be due to an inherent difference in the erythrocytes, rather than in the extent of plasma protein binding of BAA.
In Ghanayem (1989), pooled erythrocytes from 9- to 13-week-old male F344 rats and erythrocytes from healthy human volunteers (men and women 18-40 years old; n = 3) were similarly exposed to the acetic acid metabolite. At the end of the incubation period (0.25-4 hours), hematocrit and free plasma hemoglobin levels were determined as indicators of swelling of the erythrocytes and hemolysis, respectively. Comparison of thein vitro incubation data at 4 hours for rat blood (Table 1) and human blood (Table 2) suggests that the effect of 8.0 mM BAA in humans was less than that of 0.5 mM BAA in rats. Hence, humans may be at least 16 times less sensitive to the effects of BAA than rats, although information from this study is inadequate to define the exact magnitude of the species difference. It is also not clear from the data presented whether the slight changes with human erythrocytes were produced in relation to the initial control value or were compared with data for a 4-hour incubation in the absence of BAA.
Udden (1994) confirmed the lack of hemolysis in human red blood cells incubated with 2 mM BAA in groups of different human subjects, including nine healthy young adults (31-56 years old), nine older subjects (64-79 years old), seven patients with sickle cell disease and three patients with spherocytosis. Despite differences between these groups in the extent of the spontaneous hemolysis on incubation for 4 hours in the absence of BAA, in none of the groups were there significant increases in hemolysis in the presence of 2 mM BAA.
An additional investigation of Udden and Patton (1994) confirms the greater sensitivity of rat erythrocytes compared with human erythrocytes to the acetic acid metabolite of 2-butoxyethanolin vitro. The maximum concentration (2 mM) did not produce any detectable effect in human erythrocytes, although it induced rapid hemolysis in rat erythrocytes. Exposure of rat erythrocytes to 0.2 mM BAA did not result in hemolysis, although reduced cell deformability and increased mean cell volume were noted. No details were given of the human subjects who donated erythrocytes.
Table 1 Effects of concentration and time on hematocrit and the concentration of free plasma hemoglobin in rat blood incubated with butoxyacetic acid (BAA)in vitro (data from Ghanayem, 1989) Time since exposure (hours)
0.25 0.5 1.0 2.0 4.0
Hematocrit (% control)
0.5 mM BAA 104 108 110 121
1.0 mM BAA 111 117 124 144
2.0 mM BAA 111 118 133 169 <10
Plasma hemoglobin (g/dL)
0.5 mM BAA 0.2 0.2 0.2 0.5
1.0 mM BAA 0.4 0.8 1.0 2.0
2.0 mM BAA 0.6 1.0 2.2 7.0
Comparison of the data of Udden (1994) with those of Udden and Patton (1994), acquired by directly comparable protocols, indicates that the no-effect concentration for hemolysis is 2 mM BAA in human erythrocytes and 0.2 mM in rat erythrocytes. Although very few concentrations were studied, these data support at least a 10-fold difference in sensitivity between rats and humans.
2.4.3.11 Toxicokinetics and mode of action
These observed species- and sex-related variations in hematotoxicity are well correlated with differences in production and clearance of the acetic acid metabolite of 2-butoxyethanol. Mice appear to clear BAA from the blood much more quickly than rats, with the rate of elimination decreasing with increased duration of exposure to a greater degree in rats than in mice (Dill et al., 1998). Likewise, clearance of BAA from the blood is slower in female rats than in males (Dill et al., 1998); in addition, the activity of hepatic alcohol dehydrogenase enzyme, which is involved in the metabolism of 2-butoxyethanol to BAA, is greater in females than in males (Aasmoe et al., 1998). Ghanayem et al. (1987) also observed older rats to be more susceptible to the hemolytic effects of acute 2-butoxyethanol exposure, which is consistent with the greater rate of elimination of metabolites in the urine of younger rats. These observations and additional studies in which oxidation of 2-butoxyethanol to BAA is inhibited indicate that the acid metabolite is likely principally responsible for the hematological effects observed in experimental animals exposed to the compound.
The specific mode of action by which 2-butoxyethanol induces hematological effects has not been established. Induced changes are those consistent with hemolytic anemia, hemoglobinuria or increased osmotic fragility of erythrocytes. Based on their progression, which includes erythrocyte swelling, morphological changes and decreased deformability (Udden, 1996), effects are likely due to conjugation of BAA with the lipids in the membrane of erythrocytes and resulting increases in permeability to cations and water (Ghanayem, 1996).
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Table 2 Effects of concentration, time and sex on hematocrit and the concentration of free plasma hemoglobin in human blood incubated with butoxyacetic acid (BAA)in vitro (data from Ghanayem, 1989) Time since exposure (hours)
Males Females
1.0 2.0 4.0 1.0 2.0 4.0
Hematocrit (% control)
2.0 mM BAA 100.8 102.5 103.2 98.6 100.0 100.2
4.0 mM BAA 102.0 103.0 104.8 100.2 100.8 103.0
8.0 mM BAA 104.0 105.1 108.2 103.6 104.0 106.4
Plasma hemoglobin (g/dL)
2.0 mM BAA 0.12 0.13 0.20 0.14 0.15 0.17
4.0 mM BAA 0.17 0.22 0.30 0.20 0.25 0.25
8.0 mM BAA 0.40 0.42 0.53 0.35 0.39 0.44
Information on the mode of induction of lesions of the forestomach by 2-butoxyethanol in subchronic studies in rats and mice and in the chronic study in mice has not been identified. The relative roles of systemic versus local delivery (i.e., mucociliary clearance from the respiratory tract and ingestion via preening) and the putatively active metabolites, which may differ from those implicated in the induction of hematological effects, are unknown. Specific quantitative data with which to assess the relative sensitivities of the forestomach of rodents and the glandular stomach of humans to 2-butoxyethanol were also not identified.
2.4.4 Humans
Alterations in various hematological parameters were noted in several case reports involving incidental exposure to 2-butoxyethanol (Rambourg-Schepens et al., 1988; Gijsenbergh et al., 1989; Bauer et al., 1992), but not in a survey of childhood poisonings by oral doses estimated to be as high as 1850 mg/kg-bw (Dean and Krenzelok, 1992). In a recent cross-sectional survey, slight, but statistically significant, changes in some hematological parameters (hematocrit and mean corpuscular hemoglobin concentration) were observed in a group of 31 men occupationally exposed to average concentrations of 2-butoxyethanol of 3.64 or 2.20 mg/m3 compared with unexposed workers, although there was no correlation with levels of butoxyacetic acid in the urine, and information on exposure was limited to personal monitoring samples taken during only one workshift (Haufroid et al., 1997). However, in the only relevant clinical study identified, no changes in erythrocyte fragility were noted in a small number of men and women (n = 2-4) exposed to up to 195 ppm (942 mg/m3) for several hours, with observed effects limited to irritation of the eyes, nose and throat (Carpenter et al., 1956).
Other effects characteristic of poisoning with ethylene glycol (a metabolite of 2-butoxyethanol in humans), such as coma, metabolic acidosis and renal effects, as well as changes in levels of hepatic enzymes (of uncertain biological significance) have been reported in several cases or cross-sectional studies (e.g., Rambourg-Schepens et al., 1988; Collinot et al., 1996; Haufroid et al., 1997; Nisse et al., 1998).
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Here are the complete world-wide studies done on 2-B .
Human Health Effects:
Toxicity Summary:
IDENTIFICATION: 2-Butoxyethanol is a high production volume glycol ether. It is a colorless liquid that is miscible in water and soluble in most organic solvents. 2-Butoxyethanol is used widely as a solvent in surface coatings, such as spray lacquers, quick dry lacquers, enamels, varnishes, varnish removers and latex paint. HUMAN EXPOSURE: Based on limited data, ambient exposures in air are generally in the ug/cu m range. Industrial exposure of the general population to this chemical is most likely from inhalation and dermal absorption during the use of products containing 2-butoxyethanol. Levels of airborne 2-butoxyethanol in occupational settings are typically in the mg/cu m range. The results of in vitro studies indicate that human red blood cells are not as sensitive to the hemolytic effects of 2-butoxyethanol and 2-butoxyacetic acid and also that red blood cells are more sensitive to hemolysis by 2-butoxyacetic acid than to hemolysis by 2-butoxyethanol. ANIMAL STUDIES: 2-Butoxyethanol is readily absorbed following inhalation, oral or dermal exposure. The chemical is metabolized via alcohol and aldehyde dehydrogenases, with the formation of 2-butoxyacetaldehyde and 2-butoxyacetic acid, the principal metabolite, although other metabolic pathways have also been identified. This chemical has moderate acute toxicity and it is irritating to the eyes and skin; it is not a skin sensitizer. The principal effect exerted by 2-butoxyethanol and its metabolite 2-butoxyacetic acid is hematotoxicity, with the rat being the most sensitive species. In rats, adverse effects on the central nervous system, kidneys and liver occur at higher exposure concentrations than do the hemolytic effects. In animals, adverse effects on reproduction and development have not been observed at less than toxic doses. Although the results of in vitro tests for mutagenicity of 2-butoxyethanol were inconsistent, the absence of structural alerts and the negative findings from in vivo studies indicate that 2-butoxyethanol is not mutagenic.
[World Health Organization/International Programme on Chemical Safety. Concise International Chemical Assessment Document No. 10. 2-Butoxyethanol p.4 (1998)]**QC REVIEWED**Evidence for Carcinogenicity:
WEIGHT-OF-EVIDENCE CHARACTERIZATION: No reliable human epidemiological studies are available that address the potential carcinogenicity of EGBE. ... NTP /the National Toxicology Program/ (1988) reported no evidence of carcinogenic activity in male F344/N rats, and equivocal evidence of carcinogenic activity in female F344/N rats on the basis of increased combined incidences of benign and malignant pheochromocytoma (mainly benign) of the adrenal medulla. They also reported some evidence of carcinogenic activity in male B6C3F1 mice on the basis of increased incidences of hemangiosarcoma of the liver, and some evidence of carcinoma (mainly papilloma). ... because of the uncertain relevance of these tumor increases to humans, the fact that EGBE is generally negative in genotoxic tests and the lack of human data to support the findings in rodents, the human carcinogenic potential of EGBE, in accordance with the recently proposed Guidelines for Carcinogen Risk Assessment (USEPA, 1996), cannot be determined at this time, but suggestive evidence exists from rodent studies. Under existing EPA guidelines (USEPA, 1986), EGBE is judged to be a possible human carcinogen, Group C. HUMAN CARCINOGENICITY DATA: There are currently no human epidemiological studies addressing the potential carcinogenicity of EGBE.
[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) for ethylene glycol monobutyl ether (111-76-2) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 15, 2000]**QC REVIEWED**Human Toxicity Excerpts:
SYMPTOMATOLOGY: 1. Central nervous depression, although probably less prominent than with ethylene glycol. 2. No hypocalcemic tetany or metabolic acidosis with the possible exception of poisonings due to ethylene glycol monomethyl ether. 3. Nausea, vomiting, and sometimes diarrhea. 4. Prominent headache. Later abdominal and lumbar pain and costovertebral angle tenderness. 5. Transient polyuria & then oliguria, progressing to anuria. 6. Acute renal failure ... 7. Less critical pathological lesions may appear in brain, lung, liver, meninges and heart. 8. Observations in animals suggest the remote possibility of pulmonary edema, intravascular hemolysis & bone marrow depression, at least with some ether derivatives of ethylene and diethylene glycols. ... /Ethylene glycol (Group B compounds)/
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-176]**PEER REVIEWED**EXPOSURE ... TO HIGH CONCN ... OF ... VAPORS, PROBABLY IN RANGE OF 300-600 PPM FOR SEVERAL HR WOULD BE EXPECTED TO CAUSE RESP & EYE IRRITATION ... /CNS DEPRESSION/, & DAMAGE TO KIDNEY & LIVER.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3933]**PEER REVIEWED**FIRST SIGN OF ORGANIC ABNORMALITY ... RESULTING FROM EXCESSIVE EXPOSURE BY ANY ROUTE LIKELY WOULD BE ABNORMAL BLOOD PICTURE CHARACTERIZED BY ERYTHROPENIA, RETICULOCYTOSIS, GRANULOCYTOSIS, & LEUCOCYTOSIS. SOMEWHAT MORE INTENSE EXPOSURE WOULD BE LIKELY TO CAUSE FRAGILITY OF ERYTHROCYTES & HEMATURIA.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3933]**PEER REVIEWED**BONE MARROW DAMAGE. /FROM TABLE/
[Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and Lange, 1987. 176]**PEER REVIEWED**2-Butoxyethanol penetrates the skin readily, and toxic action from excessive skin exposure may be more likely than from vapor inhalation.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 163]**PEER REVIEWED**IT APPEARS THAT THIS CHEMICAL IS ONE OF THE FEW MATERIALS TO WHICH HUMAN IS MORE RESISTANT THAN THE USUAL EXPERIMENTAL ANIMALS. THIS APPEARS TO BE DUE, IN PART AT LEAST, TO THE FACT THAT HUMANS ARE MORE RESISTANT THAN ARE MOST LAB ANIMALS TO THE HEMOLYTIC EFFECTS CAUSED BY THE MATERIAL ITSELF OR ITS METABOLITE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3937]**PEER REVIEWED**... REGARDED AS MOST TOXIC GLYCOL MONOALKYL ETHER USED AS SOLVENT ... .
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 610]**PEER REVIEWED**THE EFFECTS /OF ALKYL DERIV OF ETHYLENE GLYCOL/ ... UPON THE CNS INCLUDE HEADACHE, DROWSINESS, WEAKNESS, SLURRED SPEECH, RECRUDESCENT STUTTERING, STAGGERING GAIT, TREMOR, AND BLURRED VISION. CHANGES OF PERSONALITY ARE OFTEN NOTED ... THESE CHANGES ARE SUCH THAT THE PATIENT, IN THE ABSENCE OF AN ACCURATE OCCUPATIONAL HISTORY, MAY BE TREATED FOR SCHIZOPHRENIA OR NARCOLEPSY. IN ACUTE POISONING WITH THE ETHYLENE GLYCOL MONOALKYL ETHERS, THERE IS ... RENAL INJURY: ALBUMINURIA & HEMATURIA. /ETHYLENE GLYCOL MONOALKYL ETHERS/
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 301]**PEER REVIEWED**A case of severe poisoning with ethylene glycol butyl ether after massive ingestion is described. Deep coma, metabolic acidosis, hypokalemia hemoglobinuria, oxaluria and a transitory rise in the serum creatinine level were observed. The elimination of the various metabolites butoxyacetic acid and oxalate was assessed in urine and a metabolic pattern for ethylene glycol butyl ether is suggested.
[Rambourg-Schepens MO et al; Hum Toxicol 7 (2): 187-9 (1988)]**PEER REVIEWED**The effects of 2-butoxyethanol and its metabolites, 2-butoxyacetaldehyde and butoxyacetic acid, on erythrocytes from humans were investigated in vitro. ... Incubation of human blood with butoxyacetic acid showed minimal swelling or hemolysis of erythrocytes with minimal decline in blood ATP levels at butoxyacetic acid concentrations several-fold higher than required to cause complete hemolysis of rat erythrocytes. ... Human erythrocytes are comparatively insensitive to the hemolytic effects of butoxyacetic acid in vitro.
[Ghanayem BI; Biochem Pharmacol 38 (10): 1679-84 (1989)]**PEER REVIEWED**A case of acute poisoning with ethylene glycol butyl ether is reported in a chronic alcoholic abuser. On admission the 53 yr old patient was comatose with metabolic acidosis, shock and noncardiogenic pulmonary edema confirmed by hemodynamic study. Following supportive treatment and hemodialysis the outcome was favorable. ...
[Bauer P et al; Intensive Care Med 18 (4): 250-1 (1992)]**PEER REVIEWED**In several, single, 8 hour exposures of humans at concentrations of 200 or 100 ppm, no objective effects were seen except for urinary excretion of butoxyacetic acid. No increased osmotic fragility was observed in these short term exposures. Subjectively, these concentrations were found to be uncomfortable, and mild eye, nose, and throat irritation followed exposure.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 163]**PEER REVIEWED**No clinical signs of adverse effects nor subjective complaints occurred among seven male volunteers exposed at 20 ppm for 2 hours during light physical exercise.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 163]**PEER REVIEWED**Human Toxicity Values:
The lethal oral dose /of ethylene glycols/ in humans is approximately 1.4 ml/kg, which would be equivalent to approximately 100 ml for a 70-kg person. /Ethylene glycols/
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 703]**PEER REVIEWED**Skin, Eye and Respiratory Irritations:
Irritation of eyes, nose and throat ...
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 155]**PEER REVIEWED**Medical Surveillance:
Consider the points of attack (liver, kidneys, lymphoid system, skin, blood, eyes, respiratory system) in placement and periodic physical examinations.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 155]**PEER REVIEWED**Probable Routes of Human Exposure:
The most probable route of human exposure to ethylene glycol mono-n-butyl ether is by inhalation, dermal contact and ingestion. Workplace exposures have been documented(2-6). Drinking water supplies have been shown to contain ethylene glycol mono-n-butyl ether(1).
[(1) Lucas SV; GC/MS Anal of Org in Drinking Water Concentrates and Advanced Treatment Concentrates Vol 1 USEPA-600/1-84-020A (NTIS PB85-128239) p 397 (1984) (2) Lehmann E et al; pp. 31-41 in Safety and Health Aspects of Organic Solvents. Riihimaki V, Ulfvarson U eds Alan R Liss Inc. (1986) (3) Hahn WJ, Werschulz PO; Evaluation of Alternatives to Toxic Organic Paint Strippers. NTIS PB86 219-177/AS USEPA 600/S2-86/063 (1986) (4) Clapp DE et al; Environ Health Perspective 57: 91-5 (1984) (5) Shah JJ, Heyerdahl EK; National Ambient VOC Database Update USEPA 600/3-88/010 (1988) (6) Yasuhara, A et al; Agric Bio Chem 50: 1765-70 (1986)]**PEER REVIEWED**THERE IS ... HAZARD OTHER THAN VAPOR THAT MUST NOT BE OVERLOOKED WHEN HANDLING THIS MATERIAL--THAT OF POSSIBLE ABSORPTION OF TOXIC QUANTITIES THROUGH SKIN, BECAUSE OF LOW VAPOR PRESSURE ... @ ROOM TEMP, HAZARD FROM SKIN ABSORPTION COULD WELL BE GREATER, OR CONTRIBUTE SUBSTANTIALLY TO OVER-ALL HAZARD.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3938]**PEER REVIEWED**FROM INDUST POINT OF VIEW, ONLY ONE CASE OF POSSIBLE SYSTEMIC INJURY WAS THAT OF MAN WHO WAS REPORTED ... AS HAVING HAD TWO ISOLATED ATTACKS OF HEMATURIA, WITH 5 MO INTERVAL. ... HIS EXPOSURE ... INCL BUTYL CARBITOL AS WELL AS BUTYL CELLOSOLVE.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 612]**PEER REVIEWED**OCCUPATIONAL EXPOSURES TO BUTYL CELLOSOLVE, ETHANOL, & XYLENE IN FILAMENT-DRAW DEPARTMENT OF ELECTRICAL RESISTOR MFR FACILITY DID NOT POSE A HEALTH HAZARD.
[GILLES ET AL; US NTIS PB REP; ISS PB-273739 (1976) 16 PP]**PEER REVIEWED**NIOSH (NOES Survey as of 3/28/89) has estimated that 1,680,764 workers are potentially exposed to ethylene glycol mono-n-butyl ether in the USA(1). According to the National Ambient Volatile Organic Compounds (VOCs) Database, the median workplace atmospheric concn of ethylene glycol mono-n-butyl ether is 0.075 ppbV for 14 samples(3). Workers at paint stripping operations that used stripping agents containing ethylene glycol mono-n-butyl ether were exposed to it(2).
[(1) NIOSH; National Occupational Exposure Survey (NOES) (1989) (2) Hahn WJ, Werschulz PO; Evaluation of Alternatives to Toxic Organic Paint Strippers. NTIS PB86 219-177/AS USEPA 600/S2-86/063 (1986) (3) Shah JJ, Heyerdahl EK; National Ambient VOC Database Update USEPA-600/3-88/010 (1988)]**PEER REVIEWED**Personal exposures to atmospheric ethylene glycol mono-n-butyl ether at a specialty chemical production facility in June of 1981 ranged from undetected levels to 0.1 ppm; indoor air concn within the facility were as high as 1.7 ppm(2). A national survey of workplaces in the Federal Republic of Germany showed that workers were exposed to solvents containing ethylene glycol mono-n-butyl ether with a 0.4% frequency of occurrence(1).
[(1) Lehmann E et al; pp 31-41 in Safety and Health Aspects of Organic Solvents. Riihimaki V, Ulfvarson U eds Alan R Liss Inc. (1986) (2) Clapp DE et al; Environ Health Perspective 57: 91-5 (1984)]**PEER REVIEWED**A study initiated in 1983, which surveyed the workplace atmospheres of 336 businesses in Belgium, showed that ethylene glycol mono-n-butyl ether was present in 25 of 94 air samples taken from sites that utilize printing pastes; 10 of 81 samples from where painting took place; 1 of 20 samples from automobile repair shops; and 17 of 67 samples from sites where various materials such as varnishes, sterilization agents and cleaners are employed(1). The geometric mean concn of ethylene glycol mono-n-butyl ether in the air of printing shops was 4.1 mg/cu m with a range of 1.5 to 17.7 mg/cu m; 18.8 mg/cu m with a range of 3.4 to 93.6 mg/cu m for painting areas; 5.9 mg/cu m for car repair shops; and 8.5 mg/cu m with a range of 0.2 to 1775 mg/cu m for various industries(1).
[(1) Veulemans H et al; Am Indust Hyg Assoc J 48: 671-7 (1987)]**PEER REVIEWED**Ethylene glycol mono-n-butyl ether was identified as a volatile emission from used machine cutting oils in an automobile manufacturing facility in Japan(1). Non-occupational exposures may occur among populations with contaminated drinking water supplies(2). Because ethylene glycol mono-n-butyl ether is a component of solvent based building materials such as silicone caulk(3), human exposures may occur at construction sites and areas that have undergone remodelling(SRC).
[(1) Yasuhara A et al; Agric Bio Chem 50: 1765-70 (1986) (2) Lucas SV; GC/MS Anal of Org in Drinking Water Concentrates and Advanced Treatment Concentrates Vol 1 USEPA-600/1-84-020A (NTIS PB85-128239) p 397 (1984) (3) Tichenor BA, Mason MA; JAPCA 38: 264-8 (1988)]**PEER REVIEWED**Exposure of cleaning women and cleaners of cars to ethylene glycol mono-n-butyl ether resulted in urine levels of <0.1-7.33 ppm (time-weighted averages)(1). It was established that the predominant route of exposure to ethylene glycol mono-n-butyl ether was through skin penetration(1). Ethylene glycol mono-n-butyl ether was identified in air from automotive repair shops in Sydney, Australia in 8 out of 70 samples at an average concentration of 2.0 mg/cu m(2).
[(1) Vincent R et al; Appl Occup Environ Hyg 8: 580-6 (1993) (2) Winder C, Turner PJ; Am Occup Hyg 36: 385-94 (1992)]**PEER REVIEWED**Emergency Medical Treatment:
Emergency Medical Treatment:
EMT Copyright Disclaimer: |
Portions of the POISINDEX(R) database are provided here for general reference. THE COMPLETE POISINDEX(R) DATABASE, AVAILABLE FROM MICROMEDEX, SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. Copyright 1974-1998 Micromedex, Inc. Denver, Colorado. All Rights Reserved. Any duplication, replication or redistribution of all or part of the POISINDEX(R) database is a violation of Micromedex' copyrights and is strictly prohibited. The following Overview, *** ETHYLENE GLYCOL BUTYL ETHER ***, is relevant for this HSDB record chemical. |
Life Support: |
o This overview assumes that basic life support measures have been instituted. |
Clinical Effects: |
SUMMARY OF EXPOSURE 0.2.1.1 ACUTE EXPOSURE o CHILDREN ingesting small amounts (less than 15 milliliters) of dilute household products (less than 10% ethylene glycol butyl ether (EGBE)) generally do not develop evidence of toxicity. o ADULTS - Acidosis, CNS depression, renal injury, hematuria, oxaluria, ARDS, and hypotension have been reported after ingestion of 30 to 60 mL of pure EGBE in adults. o ANIMALS - Appears to be 5 to 6 times more orally toxic than ethylene glycol in animals by weight. 1. Because metabolites are an important component in the human toxicity of ethylene glycol and presumably its ethers, comparison of relative toxicity using LD50 data cannot be reliably used to predict human experience. o OTHER ROUTES OF EXPOSURE - Absorbed through skin, lungs, and gastrointestinal tract. 1. Exposure to vapors may cause eye and mucous membrane irritation. HEENT 0.2.4.1 ACUTE EXPOSURE o Transient conjunctivitis has been reported after instillation into rabbit eyes. CARDIOVASCULAR 0.2.5.1 ACUTE EXPOSURE o Severe hypotension may develop after massive oral ingestion. Ventricular dysrhythmias were reported in one case. RESPIRATORY 0.2.6.1 ACUTE EXPOSURE o Non-cardiogenic pulmonary edema (ARDS) has been reported in one case after ingestion of 500 mL of a 9.1% solution. o Aspiration may occur following large ingestions. NEUROLOGIC 0.2.7.1 ACUTE EXPOSURE o CNS depression, including coma, may occur following massive ingestions. o Seizures have been reported following ingestions. HEPATIC 0.2.9.1 ACUTE EXPOSURE o Liver necrosis, secondary to hemolysis, has been reported in animals. GENITOURINARY 0.2.10.1 ACUTE EXPOSURE o EGBE may have somewhat more renal toxicity than other glycol ethers. ACID-BASE 0.2.11.1 ACUTE EXPOSURE o Metabolic acidosis has been consistently described after massive ingestion. HEMATOLOGIC 0.2.13.1 ACUTE EXPOSURE o Hemolytic anemia, non-hemolytic anemia, thrombocytopenia, and DIC have been reported in overdose. Erythropenia, reticulocytosis, granulocytosis, and leukocytosis may occur. More intense exposure is likely to cause fragility of erythrocytes and hematuria. REPRODUCTIVE HAZARDS o Fetal toxicity has only been observed in animals at maternally toxic doses. |
Laboratory: |
o Obtain CBC, electrolytes (particularly calcium and potassium), urinalysis (look for oxalate crystals and hemoglobin) and blood gases in all asymptomatic patients with a history of exposure or patients who are symptomatic. o Blood ethanol, methanol, and ethylene glycol levels may be useful in assessing ingestions of mixtures. o The presence of butoxyacetic acid in the urine can be considered evidence of exposure to ethylene glycol butyl ether (EGBE). |
Treatment Overview: |
ORAL EXPOSURE o ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old. o Animal data are suggestive that ethanol therapy may inhibit the formation of toxic metabolites. 1. LOADING DOSE (INTRAVENOUS) - Administer 7.6 to 10 mL/kg IV of 10% ETOH in D5W over 30 minutes to achieve a blood ETOH concentration of 100 to 130 mg/dL (21.7 to 28.2 mmol/L). A loading dose of 10 mL/kg of 10% ETOH should produce a peak blood ethanol level of about 130 mg/dL (28.2 mmol/L) depending on the rate of administration. 2. LOADING DOSE (ORAL) - Administer 0.80 to 1.0 mL/kg orally of 95% ETOH in 6 oz of orange juice over 30 minutes. Begin the maintenance infusion concurrent with the loading dose. 3. PRECAUTION - Monitor blood glucose and ethanol during ethanol therapy, ethanol induced hypoglycemia may occur in children. o MONITOR - ARTERIAL pH and BLOOD GASES in symptomatic patients, or following large ingestions of EGBE. o ACIDOSIS - Treat acidosis with IV sodium bicarbonate. Begin with 1 to 2 mEq/kg in adults and 1 mEq/kg in children, repeat every 1 to 2 hours as required. Monitor blood gases to adjust dose. o FOMEPIZOLE - 1. Fomepizole is a specific antagonist of alcohol dehydrogenase is an alternative to ethanol but is not FDA approved for the treatment of ethylene glycol ether poisonings. a. DOSE - In one study a loading dose of 15 milligrams/kilogram intravenous infusion over 30 minutes is followed by doses of 10 milligrams/kilogram every 12 hours for 4 doses, then 15 milligrams/kilogram every 12 hours until ethylene glycol levels are below 20 milligrams/deciliters. Dose needs to be adjusted during hemodialysis. See main treatment section. o THIAMINE/PYRIDOXINE - 1. Administer thiamine and pyridoxine 100 mg IV daily. o HEMODIALYSIS - 1. Has not been shown to effectively remove EGBE but may be used to correct severe acid-base and/or fluid-electrolyte abnormalities that persist despite conventional therapy. |
Range of Toxicity: |
o ORAL - Available animal data suggest that, based on comparisons of oral LD50 values in the same species, ethylene glycol butyl ether is 5 to 6 times more acutely toxic than ethylene glycol; however, this model does not account for toxicity of metabolites. o Severe toxicity has been described in adults who ingested 30 to 63.5 mL of pure EGBE. o Children ingesting small amounts (less than 10 milliliters) of dilute household products (less than 10% ethylene glycol butyl ether) generally do not develop evidence of poisoning. |
[Rumack BH: POISINDEX(R) Information System. Micromedex, Inc., Englewood, CO, 2002; CCIS Volume 113, edition exp August, 2002. Hall AH & Rumack BH (Eds):TOMES(R) Information System. Micromedex, Inc., Englewood, CO, 2002; CCIS Volume 113, edition exp August, 2002.] **PEER REVIEWED**Animal Toxicity Studies:
Toxicity Summary:
IDENTIFICATION: 2-Butoxyethanol is a high production volume glycol ether. It is a colorless liquid that is miscible in water and soluble in most organic solvents. 2-Butoxyethanol is used widely as a solvent in surface coatings, such as spray lacquers, quick dry lacquers, enamels, varnishes, varnish removers and latex paint. HUMAN EXPOSURE: Based on limited data, ambient exposures in air are generally in the ug/cu m range. Industrial exposure of the general population to this chemical is most likely from inhalation and dermal absorption during the use of products containing 2-butoxyethanol. Levels of airborne 2-butoxyethanol in occupational settings are typically in the mg/cu m range. The results of in vitro studies indicate that human red blood cells are not as sensitive to the hemolytic effects of 2-butoxyethanol and 2-butoxyacetic acid and also that red blood cells are more sensitive to hemolysis by 2-butoxyacetic acid than to hemolysis by 2-butoxyethanol. ANIMAL STUDIES: 2-Butoxyethanol is readily absorbed following inhalation, oral or dermal exposure. The chemical is metabolized via alcohol and aldehyde dehydrogenases, with the formation of 2-butoxyacetaldehyde and 2-butoxyacetic acid, the principal metabolite, although other metabolic pathways have also been identified. This chemical has moderate acute toxicity and it is irritating to the eyes and skin; it is not a skin sensitizer. The principal effect exerted by 2-butoxyethanol and its metabolite 2-butoxyacetic acid is hematotoxicity, with the rat being the most sensitive species. In rats, adverse effects on the central nervous system, kidneys and liver occur at higher exposure concentrations than do the hemolytic effects. In animals, adverse effects on reproduction and development have not been observed at less than toxic doses. Although the results of in vitro tests for mutagenicity of 2-butoxyethanol were inconsistent, the absence of structural alerts and the negative findings from in vivo studies indicate that 2-butoxyethanol is not mutagenic.
[World Health Organization/International Programme on Chemical Safety. Concise International Chemical Assessment Document No. 10. 2-Butoxyethanol p.4 (1998)]**QC REVIEWED**Evidence for Carcinogenicity:
WEIGHT-OF-EVIDENCE CHARACTERIZATION: No reliable human epidemiological studies are available that address the potential carcinogenicity of EGBE. ... NTP /the National Toxicology Program/ (1988) reported no evidence of carcinogenic activity in male F344/N rats, and equivocal evidence of carcinogenic activity in female F344/N rats on the basis of increased combined incidences of benign and malignant pheochromocytoma (mainly benign) of the adrenal medulla. They also reported some evidence of carcinogenic activity in male B6C3F1 mice on the basis of increased incidences of hemangiosarcoma of the liver, and some evidence of carcinoma (mainly papilloma). ... because of the uncertain relevance of these tumor increases to humans, the fact that EGBE is generally negative in genotoxic tests and the lack of human data to support the findings in rodents, the human carcinogenic potential of EGBE, in accordance with the recently proposed Guidelines for Carcinogen Risk Assessment (USEPA, 1996), cannot be determined at this time, but suggestive evidence exists from rodent studies. Under existing EPA guidelines (USEPA, 1986), EGBE is judged to be a possible human carcinogen, Group C. HUMAN CARCINOGENICITY DATA: There are currently no human epidemiological studies addressing the potential carcinogenicity of EGBE.
[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) for ethylene glycol monobutyl ether (111-76-2) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 15, 2000]**QC REVIEWED**Non-Human Toxicity Excerpts:
Tests of the liquid by dropping on rabbit eyes induces reddening and swelling of the conjunctiva with slight clouding of the corneal epithelium. The degree of injury judged 24 hours after the application of a single drop has been graded 4 on a scale of 1 to 10. Rabbit eyes in contact with the liquid for eight minutes before irrigation with water have recovered completely in four days.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 163]**PEER REVIEWED**ON EXCISED BEEF CORNEA ... /IT REDUCED/ ADHESION OF EPITHELIUM TO STROMA ... .
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 163]**PEER REVIEWED**... RATS OF DIFFERENT AGES /WERE EXPOSED/ TO VARIOUS CONCN OF VAPOR. ... 1-YR-OLD RATS WERE MORE SUSCEPTIBLE THAN YOUNG, ACTIVELY GROWING RATS. AT ... 375 PPM OLD ADULTS DIED AFTER 7 HR WHILE 6-WK-OLD RATS SURVIVED 8 HR AT 500 PPM.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3935]**PEER REVIEWED**... REPEATED INHALATION STUDIES ... AT HIGH CONCN, RATS EXHIBITED HEMORRHAGE OF LUNG, CONGESTION OF VISCERA, LIVER INJURY, HEMOGLOBINURIA, & MARKED ERYTHROCYTE FRAGILITY. FEMALES WERE MORE SENSITIVE THAN MALES.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3935]**PEER REVIEWED**GUINEA PIGS ... AT HIGH CONCN, CONGESTION & CLOUDY SWELLING OF TUBULES OF KIDNEYS ... BUT NO INCR IN FRAGILITY OF ERYTHROCYTES ... @ ANY CONCN STUDIED. MICE WERE ... AS RESISTANT AS GUINEA PIGS, WITH EXCEPTION THAT THEIR ERYTHROCYTES WERE AS FRAGILE AS THOSE OF RAT.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3935]**PEER REVIEWED**... RATS /WERE MAINTAINED/ ... ON DIETS CONTAINING 2.0, 0.5, 0.125, & 0.03% ... AT TOP LEVEL, GROWTH DEPRESSION & INCR KIDNEY & LIVER WEIGHTS ... AT 0.5% ... GROWTH DEPRESSION & INCR LIVER WT ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3933]**PEER REVIEWED**... 2 DOGS /WERE/ EXPOSED TO VAPOR CONCN OF 415 PPM 7 HR/DAY, 5 DAYS/WK, FOR 12 WK. ... THERE WAS INCR IN NUMBER OF CALCIUM OXALATE CRYSTALS IN URINE & ... RETENTION OF UREA IN BLOOD ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3935]**PEER REVIEWED**DOGS EXPOSED TO HIGH CONCN SUFFERED CONGESTION OF KIDNEYS & LUNG, WT LOSS, INCR FRAGILITY OF ERYTHROCYTES, NASAL & EYE INFECTIONS, APATHY, ANOREXIA, NAUSEA, & ... CHANGES IN CIRCULATING BLOOD. LEUCOCYTES ... INCR. WHEREAS ... HEMOGLOBIN ... DECR. ... INCR IN PLASMA FIBRINOGEN.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3937]**PEER REVIEWED**MONKEYS EXPOSED TO 200 PPM SUFFERED MARKED REDUCTION IN NUMBER OF CIRCULATING RED BLOOD CELLS & IN HEMOGLOBIN CONCN. ... FEMALE MONKEYS EXCRETED 309 MG OF BUTOXYACETIC ACID OVER A 48-HR PERIOD AFTER RECEIVING THE 48-HR EXPOSURE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3937]**PEER REVIEWED**CHRONIC. LUNG ... SLIGHT TO MODERATE CONGESTION; SOMETIMES BRONCHOPNEUMONIA. SPLEEN, CONGESTION & FOLLICULAR PHAGOCYTOSIS ... .
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 612]**PEER REVIEWED**... BY INHALATION /MEDIAN LETHAL DOSE/, FOR RATS, 432 PPM 7 HR/DAY, 5 DAYS/WK FOR 30 DAYS; FOR GUINEA PIGS, 494 PPM KILLED ONLY 2 OUT OF 10; FOR DOGS, 617 PPM AFTER 13 1/2 HR EXPOSURES IN 2 DAYS. ACUTE. SLUGGISHNESS, ROUGH COAT, PROSTRATION & ... /CNS DEPRESSION/ IN HIGH CONCN ... CORNEAL OR LENS OPACITY.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 611]**PEER REVIEWED**ACUTE. SLUGGISHNESS, ROUGH COAT, PROSTRATION & ... /SRP: CNS DEPRESSION/ IN ANIMALS DYING FROM ORAL DOSE ... IN MICE ... DYSPNEA WAS CONSTANT SIGN & WITH HIGH CONCN ... CORNEAL OR LENS OPACITY.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 611]**PEER REVIEWED**INHALATION (84 MG/CU M, 6 HR DAILY, 3 DAYS/WK, FOR 4 MO) CAUSED ADAPTATION IN RATS & MICE, PROBABLY CONSISTING OF CHANGES OF ENZYME SYSTEMS OF ERYTHROCYTES, PROTECTING HEMOGLOBIN & ERYTHROCYTE MEMBRANE FROM PEROXIDATION. 3-HR, 6 DAYS/WK FAILED TO INDUCE ADAPTATION.
[LOMONOVA ET AL; GIG TR PROF ZABOL 2: 38 (1977)]**PEER REVIEWED**HIGH DOSES OF ORALLY ADMIN ETHYLENE GLYCOL MONOALKYL ETHERS PRODUCED TESTICULAR ATROPHY & LEUKOPENIA IN MICE. A DOSE RESPONSE RELATION WAS OBSERVED. /ETHYLENE GLYCOL MONOALKYL ETHERS/
[NAGANO K ET AL; SANGYO IGAKU 21 (1): 29 (1979)]**PEER REVIEWED**Fifty pregnant CD-1 mice were given 1,180 mg/kg/day of ethylene glycol monobutyl ether in water by gavage on days 6-13 of gestation and allowed to deliver. Ethylene glycol monobutyl ether caused 20% mortality in treated dams but had no effect on the offspring of treated animals.
[Hardin BD et al; Teratog Carcinog Mutagen 7: 29-48 (1987)]**PEER REVIEWED**The reproductive effects of ethylene glycol monomethyl ether and propylene glycol monomethyl ether inhalation were investigated in rats. To determine the effects on testis and hematology, male Wistar rats were exposed to 100 or 300 ppm ethylene glycol monomethyl ether or 200 or 600 ppm propylene glycol monomethyl ether for 6 hr per day for 10 consecutive days in an inhalation chamber. The teratogenic potential on the developing embryo was assessed by exposing pregnant female rats to 100 or 300 ppm ethylene glycol monomethyl ether and 200 or 600 ppm propylene glycol monomethyl ether for 6 hr per day on days 6 to 17 of gestation. Other studies investigated the teratogenic potential of diethylene ethylene monomethyl ether in the postnatal development test, effect on route of administration on teratogenic potential of ethylene glycol monomethyl ether, effect of ethylene glycol monoisopropyl ether on the testis and blood, effect of a single inhalation exposure to ethylene glycol monomethyl ether, ethylene glycol monoisopropyl ether, ethylene glycol monomethyl ether, and ethylene glycol monobutyl ether, and exposure of a single exposure to ethylene glycol monomethyl ether on the testis of male rats. Ethylene glycol monomethyl ether caused testicular atrophy at 300 ppm and showed teratogenic potential at 100 ppm; propylene glycol monomethyl ether did not cause testicular atrophy or affect embryonic development at 600 ppm by inhalation. Diethylene glycol monomethyl ether showed no teratogenic potential when administered subutaneously in rats up to 1,000 ul/kg, whereas ethylene glycol monomethyl ether had effects at 40 ul/kg. Ethylene glycol monomethyl ether caused testicular changes in rats after a single exposure to 600 ppm or more for 4 hr. Ethylene glycol monoethyl ether caused a reduction in testicular weight following a single exposure to saturated vapor of 17 mg/l for 3 hours; ethylene glycol monoisopropyl ether at 15 mg/l and ethylene glycol monobutyl monobutyl ether at 4 mg/l showed no effect on the testis.
[Doe JE; Environ Health Perspect 57: 199-206 (1984)]**PEER REVIEWED**Previous NIOSH studies demonstrated the embryo- and fetotoxicity and teratogenicity of ethylene glycol monoethyl ether applied to the shaved skin of pregnant rats. In the present study ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether, and diethylene glycol monoethyl ether were tested in the same experimental model, using distilled water as the negative control and ethylene glycol monoethyl ether as a positive control. Water or undiluted glycols were applied four times daily on days 7 to 16 gestation to the shaved interscapular skin with automatic pipetter. Volumes of ethylene glycol monoethyl ether (0.25 ml), ethylene glycol monoethyl ether acetate (0.35 ml), and diethylene glycol monoethyl ether (0.35 ml) were approximately equimolar (2.6 mmole per treatment). Ethylene glycol monobutyl ether at 0.35 ml four times daily (approximately 2.7 mmole per treatment) killed 10 of 11 treated rats, and was subsequently tested at 0.12 ml (0.9 mmole) per treatment. Ethylene glycol monoethyl ether and ethylene glycol monoethyl ether acetate treated rats showed a reduction in body weight relative to water controls that was associated with completely resorbed litters and significantly fewer live fetuses per litter. Visceral malformations and skeletal variations were significantly increased in ethylene glycol monoethyl ether and ethylene glycol monoethyl ether acetate groups over the negative control group. No embryotoxic, fetotoxic, or teratogenic effects were detected in the ethylene glycol monobutyl ether or diethylene glycol monoethyl ether treated litters.
[Hardin BD et al; Environ Health Perspect 57: 69-74 (1984)]**PEER REVIEWED**Mice were intubated during gestation and were evaluated for signs of toxicity. In the teratology probe, uterine contents were examined at term. In the postnatal study, offspring were examined and weighed through day 22 postpartum. Ethylene glycol monoethyl ether produced embryo lethality and malformations, and decreased fetal weight at a dose level which was not maternally toxic in the teratology probe. In the postnatal study, ethylene glycol monoethyl ether decreased litter size and neonatal body weight; while litter size continued to decrease beyond neonatal period, body weights of surviving pups were not significantly different from control. Pups exposed prenatally to ethylene glycol monoethyl ether developed kinked tail which was not apparent in fetuses or neonates. Maternally toxic doses levels of ethylene glycol monobutyl ether ethanol were associated with increased embryo lethality in teratology probe studies. In postnatal studies, there were no significant effects on pup growth or survival at maternally toxic dose levels. The teratology probe measures resorption incidence which may be a more sensitive index of prenatal death than number of live born. Neither fetal weight nor neonatal weight reliably predict permanent alteration of growth.
[Wier PJ et al; Teratogenesis Carcinog Mutagen 7 (1): 55-64 (1987)]**PEER REVIEWED**Structure activity studies with nine glycol alkyl ethers were conducted with a cellular leukemia transplant model in male Fischer rats to measure the effects on neoplastic progression in transplant recipients. Chemicals were given ad libitum in the drinking water simultaneously with the transplants and continued throughout the study. In all 20 million leukemic cells were injected sc into syngeneic rats, which after 60 days resulted in a 10-fold increase in relative spleen weights, a 100-fold increase in white blood cell counts, and a 50% reduction in red blood cell indices and platelet counts. Ethylene glycol monomethyl ether given at a dose of 2.5 mg/ml in the drinking water completely eliminated all clinical, morphological, and histopathological evidence of leukemia, whereas the same dose of ethylene glycol monoethyl ether reduced these responses by about 50%. Seven of the glycol ethers were ineffective as anti-leukemic agents, including ethylene glycol, the monopropyl, monobutyl, and monophenyl ethylene glycol ethers, diethylene glycol, and the monomethyl and monoethyl diethylene glycol ethers. Ethylene glycol monomethyl ether more than double the latency period of leukemia expression and extended survival for at least 21 days. A minimal effective dose for a 50% reduction in the leukemic responses was 0.25 mg/ml ethylene glycol monomethyl ether in the drinking water (15 mg/kg body weight), whereas a 10-fold higher dose of 2-ethylene glycol monoethyl ether was required for equivalent antileukemic activity. In addition, the in vitro exposure of a leukemic spleen mononuclear cell culture to ethylene glycol monomethyl ether caused a dose- and time-dependent reduction in the number of leukemia cells after a single exposure to 1-100 uM concentrations, whereas the ethylene glycol monomethyl ether metabolite, 2-methoxyacetic acid, was only half as effective.
[Dieter MP et al; Cancer Chemother Pharmacol 26 (3): 173-80 (1990)]**PEER REVIEWED**Studies were conducted on the percutaneous absorption, distribution, excretion, and hemolytic activity of n-butoxyethanol. Rats receiving a subcutaneous dose of (14)C-labeled n-butoxyethanol excreted the radioactivity in the urine (79%), expired air (10%), and feces (0.5%) within 72 hr. Of the organs analyzed, thymus and spleen showed elevated specific radioactivities as compared with blood. A percutaneous application of n-butoxyethanol on rats, under nonocclusive conditions, showed 25-29% absorption within 48 hr. Peak blood levels of n-butoxyethanol occurred at 2 hr after application; butoxyacetic acid was found to be the major metablite. Comparison of in vitro skin penetration data showed the following absorption pattern of n-butoxyethanol: hairless rat much greater than pig greater than human skin. Hemolysis and associated hematological changes were noted in the rats which received single dermal applications of 260-500 mg/kg of n-butoxyethanol. In vitro, butoxy acetic acid showed markedly greater hemolytic ability on rat erythrocytes than did n-butoxyethanol. Human erythrocytes showed no hemolysis when incubated with n-butoxyethanol or butoxy acetic acid at concentrations that are hemolytic to rat erythrocytes. An intravenous dose of 62.5 mg/kg of n-butoxyethanol does not result in hemolysis or hemoglobinuria in the rat. The rat may be an animal model with increased susceptibility to the effects of n-butoxyethanol compared with humans because of its rapid percutaneous absorptive ability and its greater hemolytic sensitivity.
[Bartnik FG et al; Fundam Appl Toxicol 8 (1): 59-70 (1987)]**PEER REVIEWED**2-Butoxyethanol causes acute hemolytic anemia in rats, and activation of 2-butoxyethanol to butoxyacetic acid, presumably through the intermediate 2-butoxyacetaldehyde, is a prerequisite for development of hematotoxicity. The effects of 2-butoxyethanol and its metabolites, 2-butoxyacetaldehyde and butoxyacetic acid, on erythrocytes from rats were investigated in vitro. At 20 mM, 2-butoxyethanol caused hemolysis of rat erythrocytes accompanied by a decrease in hematocrit. In contrast, incubation of 2-butoxyacetaldehyde or butoxyacetic acid with rat blood caused time- and concentration-dependent swelling of red blood cells followed by hemolysis; butoxyacetic acid was significantly more efficacious than 2-butoxyacetaldehyde. Addition of aldehyde dehydrogenase and its co-factors potentiated the effect of 2-butoxyacetaldehyde on rat erythrocytes. Incubation of rat blood with butoxyacetic acid or 2-butoxyacetaldehyde cused a time- and concentration-dependent decrease in blood ATP concentration. The decrease in blood ATP was greater with butoxyacetic acid than with 2-butoxycetaldehyde and was not induced by 2-butoxyethanol. Butoxyacetic acid caused no significant changes in the concentration of reduced glutathione and glucose-6-phosphate dehydrogenase in rat erythrocytes. The hemolytic effect of 2-butoxyethanol can be attributed primarily to its metabolite butoxyacetic acid, and hemolysis of rat erythrocytes by butoxyacetic acid or 2-butoxyacetaldehyde is preceded by swelling and ATP depletion.
[Ghanayem BI; Biochem Pharmacol 38 (10): 1679-84 (1989)]**PEER REVIEWED**Male rats were given ethylene glycol monomethyl ether or ethylne glycol monobutyl ether per os for 4 consecutive days at doses of 100 or 500 mg/kg body wt/day for ethylene glycol monobutyl ether, and 500 or 1000 mg/kg body wt/day for ethylene glycol monobutyl ether. Animals were examined on days 1, 4, 8, and 22 after the final treatment. Both ethylene glycol monomethyl ether and ethylene glycol monobutyl ether produced thymic atrophy and lymphocytopenia and, in the case of ethylene glycol monobutyl ether, neutropenia also. Hemolytic anemia induced by ethylene glycol monobutyl ether resulted in splenic extramedullary hemopoiesis, hyperplasia of both spleen and bone marrow, and reticulocytosis. Apart from residual slight increases in spleen weight, mean red cell volume, and mean corpuscular hemoglobin at the end of the recovery period, other effects were reversible. With ethylene glycol monomethyl ether, reduction in the numbers of circulating red cells was only slight. Treatment with ethylene glycol monomethyl ether also abolished splenic extramedullary hemopoiesis which partially recovered on day 4, followed by a marked response on day 8, and return to the control values on day 22. Femoral bone marrow was hemorrhagic 1 day after treatment with ethylene glycol monomethyl ether which appeared to be associated with sinus endothelial cell damage. By day 4 the histologic appearance of the marrow was normal. Testicular atrophy was also produced in ethylene glycol monomethyl ether-treated animals. Ethylene glycol monomethyl ether and ethylene glycol monobutyl ether differ considerably in the spectrum of toxic changes induced, and apart from testicular atrophy, these changes were largely reversible within a short time of the end of treatment.
[Grant D et al; Toxicol Appl Pharmacol 77 (2): 187-200 (1985)]**PEER REVIEWED**Structurally related alkyl glycol ethers were examined for their ability to block junction-mediated intercellular communication. Interruption of intercellular communication was measured in vitro by an assay that depends on the transfer of metabolites via gap junctions, ie, metablic cooperation. All compounds tested ethylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, and ethylene glycol monobutyl ether were able to block metabolic cooperation in vitro. The potencies of the compounds were inversely related to the length of the aliphatic chain, the dose required for maximum blockage increasing as the aliphatic chain shortened. Cytotoxicity, as measured by cell survival, was also related to the structure of the compound, generally increasing with increased length of the aliphatic chain.
[Loch-Caruso R et al; Environ Health Perspect 57: 119-23 (1984)]**PEER REVIEWED**Timed-pregnant Fischer 344 rats and New Zealand White rabbits were exposed to ethylene glycol monobutyl ether vapors by inhalation on gestational days 6 through 15 (rats) or 6 through 18 (rabbits) at concentrations of 0, 25, 50, 100 or 200 ppm. The animals were sacrificed on gestational day 21 (rats) or 29 (rabbits). In rats, exposure to 200 or 100 ppm resulted in maternal toxicity (clinical signs, decreased body weight and weight gain, decreased absolute and relative organ weights, decreased food and water consumption and evidence of anemia), embryotoxicity (increased number of totally resorbed litters and decreased number of viable implantations per litter) and fetotoxicity (reductions in skeletal ossification). No increase in fetal malformations was observed in any exposure group relative to controls. At 50 or 25 ppm, there was no maternal, embryo or fetal toxicity (including malformations) in rats. In rabbits, exposure to 200 ppm resulted in maternal toxicity (apparent exposure-related increases in deaths and abortions, clinical signs, decreased weight during exposure and reduced gravid uterine weight at sacrifice) and embryotoxicity (reduced number of total and viable implantations per litter). No treatment-related fetotoxicity was seen. No treatment-related increase in fetal malformations or variations were seen at any exposure concentration tested. There was no evidence of maternal, embryo, or fetal toxicity (including malformations) at 100, 50 or 25 ppm in rabbits.
[Tyl RW et al; Environ Health Perspect 57: 47-68 (1984)]**PEER REVIEWED**Investigated the teratogenicity of five compounds. Each chemical was vaporized and administered to pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occured at both 100 and 50 ppm. 2-Ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. Shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether.
[Nelson BK et al; Environ Health Perspect 57: 261-71 (1984)]**PEER REVIEWED**In F344 male rats, 2-butoxyethanol causes severe acute hemolytic anemia resulting in significant increase in the concentration of free plasma hemoglobin. Secondary to the hemolytic effects, 2-butoxyethanol also caused hemoglobinuria as well as histopathologic changes in the liver and kidney. The hemolytic effects of 2-butoxyethanol were age dependent with older rats being more sensitive than younger rats. There was a higher portion of the administered dose eliminated as carbon dioxide a higher portion of the administered dose was excreted in the urine of young rats. Analysis of the urinary metabolites showed that the ratio of butoxyacetic acid 2-butoxyethanol glucuronide + 2-butoxyethanol sulfate (previously thought to reflect an activation/detoxification index of 2-butoxyethanol) was higher in old rats. The increase in the activation/detoxification index in older rats is caused by decreased degradation of butoxyacetic acid to carbon dioxide and by depressed urinary excretion of butoxyacetic acid in the urine of older rats.
[Ghanayem BI et al; Toxicol Appl Pharmacol 91 (2): 222-34 (1987)]**PEER REVIEWED**2-Butoxyethanol given orally to mice for 5 weeks at a dose of 1000 mg/kg produced no change in absolute or relative testis weights.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 162]**PEER REVIEWED**Exposure of pregnant rats at 100 ppm or rabbits at 200 ppm during organogenisis resulted in maternal toxicity and embryotoxicity, including a decrease number of viable implantations per litter. Slight fetotoxicity in the form of poorly ossified or unossified skeletal elements was also observed in rats. Teratogenic effects were not observed in either species.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 162]**PEER REVIEWED**... ... Conclusions: Under the conditions of these 2 yr inhalation studies, there was no evidence of carcinogenic activity of 2-butoxyethanol in male F344/N rats exposed to 31.2, 62.5 or 125 ppm. There was equivocal evidence of carcinogenic activity of 2-butoxyethanol in female F344/N rats based on incr incidences of benign or malignant pheochromocytoma (mainly benign) of the adrenal medulla. There was some evidence of carcinogenic activity of 2-butoxyethanol in male B6C3F1 mice based on incr incidences of hemangiosarcoma of the liver. ... There was some evidence of carcinogenic activity of 2-butoxyethanol in female B6C3F1 mice based on incr incidences of forestomach squamous cell papilloma or carcinoma (mainly papilloma).
[Toxicology & Carcinogenesis Studies of 2-Butoxyethanol in F344/N Rats and B6C3F1 Mice p.6 Technical Report Series No. 484 (2000) NIH Publication No. 00-3974 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**QC REVIEWED**National Toxicology Program Studies:
... 2 Year Study in Rats: Groups of 50 male and 50 female F344/N rats were exposed to 2-butoxyethanol by inhalation at concn of 0, 31.2, 62.5 or 125 ppm 6 hr/day, 5 days per week for 104 weeks. ... 2 Year Study in Mice: Groups of 50 male and 50 female B6C3F1 mice were exposed to 2-butoxyethanol by inhalation at concn of 0, 62.5, 125 or 250 ppm 6 hr/day 5 days per week for 104 weeks. ... Conclusions: Under the conditions of these 2 yr inhalation studies, there was no evidence of carcinogenic activity of 2-butoxyethanol in male F344/N rats exposed to 31.2, 62.5 or 125 ppm. There was equivocal evidence of carcinogenic activity of 2-butoxyethanol in female F344/N rats based on incr incidences of benign or malignant pheochromocytoma (mainly benign) of the adrenal medulla. There was some evidence of carcinogenic activity of 2-butoxyethanol in male B6C3F1 mice based on incr incidences of hemangiosarcoma of the liver. ... There was some evidence of carcinogenic activity of 2-butoxyethanol in female B6C3F1 mice based on incr incidences of forestomach squamous cell papilloma or carcinoma (mainly papilloma).
[Toxicology & Carcinogenesis Studies of 2-Butoxyethanol in F344/N Rats and B6C3F1 Mice p.6 Technical Report Series No. 484 (2000) NIH Publication No. 00-3974 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**QC REVIEWED**Non-Human Toxicity Values:
LD50 Rat oral 1.48 g/kg
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 239]**PEER REVIEWED**LD50 Mouse oral 1.2 g/kg
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 315]**PEER REVIEWED**LD50 Rabbit oral 0.32 g/kg
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 315]**PEER REVIEWED**LD50 Guinea pig oral 1.2 g/kg
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 315]**PEER REVIEWED**LD50 Rabbit dermal 400 mg/kg
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 162]**PEER REVIEWED**Ecotoxicity Values:
LC50 Lepomis macrochirus 1490 ppm/96 hr. (Static bioassay in fresh water at 23 deg C, mild aeration applied after 24 hr).
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 315]**PEER REVIEWED**LC50 Menidia beryllina 1250 ppm/96 hr (static bioassay in synthetic seawater at 23 deg C, mild aeration applied after 24 hr).
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 315]**PEER REVIEWED**LC50 Crangon crangon (brown shrimp) 800 mg/l/48 hr (range: 600-1000 mg/l). /Conditions of bioassay not specified/
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 314]**PEER REVIEWED**LC50 Poecilia reticulata (guppy) 983 ppm/7 day. /Conditions of bioassay not specified/
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 314]**PEER REVIEWED**TSCA Test Submissions:
Teratogenicity was evaluated in mated Fischer 344 rats (30/group) exposed by inhalation to ethylene glycol mono-butyl ether (EGBE) at nominal concentrations (number of pregnant rats) of 0 (21), 100 (21), 200 (16) or 300 (24) ppm on gestation days (GD) 6-15 for 6 hrs/day. The rats were sacrificed on GD 21. There were significant differences observed between pregnant treated and control animals in the following: decreased maternal body weight gain and decrease in food consumption (all treated groups during exposure), increased food consumption (200 and 300 ppm groups, post-exposure), decreased water consumption (200 and 300 ppm, exposure period), decreased uterine and liver absolute weights (300 ppm), increased non-viable implantations and percent pre-implantation loss and decreased viable implantations and percent live implantations (300 ppm), increased incidence of ventricular septal defect, and absent and severely shortened innominate artery (300 ppm). There were no significant differences observed between pregnant treated and control animals in the following: post-exposure water consumption, weights of thymus and spleen, relative weights of uterus and liver, numbers of corpora lutea, and total implantations.
[Bushy Run Research Center, Union Carbide Corp.; Inhalation Teratological Potential of Ethylene Glycol Monobutyl Ether in the Rat. (1983), EPA Document No. 88-8300481, Fiche No. OTS0503697] **UNREVIEWED**Teratogenicity was evaluated in pregnant Fischer 344 rats (36/group) exposed by inhalation to ethylene glycol mono-butyl ether (EGBE) at nominal concentrations of 0, 25, 50, 100 or 200 ppm on gestation days (GD) 6-15. The rats were sacrificed on GD 21. There were significant differences observed between treated and control animals in the following: increase in number of totally resorbed litters (200 ppm group), increased incidence of clinical observations including cold and pale extremities, abnormal tails, fur and urogenital areas stained, urogenital wetness and encrustation, occult blood (200 ppm), periocular wetness and perinasal encrustation (100 and 200 ppm), decreased body weight (200 ppm), decreased body weight gain (100 and 200 ppm, exposure period, 200 ppm post-exposure period also), decreased food consumption (100 and 200 ppm, exposure period), increased water consumption (100 ppm, post-exposure), decreased gravid uterine weight and increased relative and absolute spleen and relative kidney weights (200 ppm), decreased red blood cell count and mean corpuscular hemoglobin volume and increased mean corpuscular volume and corpuscular hemoglobin level (100 and 200 ppm), increased hemoglobin and hematocrit levels (200 ppm), decreased viable implants and percent live fetuses and increased non-viable implants and embryonic resorptions (200 ppm), increased number of litters with 1 or more cases of unossified skeletal elements (100 and 200 ppm) including anterior arch of the atlas and cervical centra, cervical arches, sternebrae, and proximal phalanges (200 ppm), unossified cervical centrum (100 ppm), and decreased incidence of bilobed cervical centrum 5 (100 and 200 ppm). There were no significant differences observed between treated and control animals in the following: pregnancy rates, early deliveries, dead fetuses, liver and thymus and absolute kidney weights, numbers of corpora lutea, total implants, dead fetuses, pre-implantation loss, fetal sex ratio, mean litter weight, external, visceral, skeletal or total malformations.
[Bushy Run Research Center, Union Carbide Corp.; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. 88-8400598, Fiche No. OTS0503697] **UNREVIEWED**Teratogenicity was evaluated in pregnant New Zealand white rabbits (24/group) exposed by inhalation to ethylene glycol mono-butyl ether (EGBE) at nominal concentrations of 0, 25, 50, 100 or 200 ppm on gestation days (GD) 6-18. The rats were sacrificed on GD 29. There were significant differences observed between treated and control animals in the following: decreased maternal body weight (200 ppm group on GD 15), increased hemoglobin and hematocrit levels (100 ppm group), decreased gravid uterine weight (200 ppm), reduced number of total implants and viable implants/litter (200 ppm), increased number of litters with fusion of papillary muscles in left ventricle (100 ppm), and reduced ossification of sternebra 6 and rudimentary rib (200 ppm). There were no significant differences observed between treated and control animals in the following: maternal mortality, number of spontaneous abortions, pregnancy rates, maternal body weight gain, number of non-viable implants, pre-implantation losses, percent live fetuses, sex ratio, fetal body weights/litter, and number of fetuses or of litters with one or more affected fetuses with pooled external, visceral, skeletal or total malformations.
[Bushy Run Research Center, Union Carbide Corp.; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. 88-8400598, Fiche No. OTS0503697] **UNREVIEWED**Acute oral toxicity was evaluated in 4 groups of 10 male albino rats (Wistar strain) administered PolySolv EB (ethylene glycol mono-n-butyl ether) by gavage at 0.67, 1.31, 2.56 and 5.0 g/kg dose levels. Mortality was observed within 14 days of dosing in 3 rats at the 1.31 g/kg dose level, 8 rats at the 2.56 g/kg dose level and all rats at the 5.0 g/kg dose level. The LD50 was calculated to be 1.59 g/kg with 95% confidence limits of 1.11 - 2.27 g/kg. Clinical observations include piloerection and lethargy at the 1.31 and 2.56 g/kg dose levels, flaccidity at the 2.56 g/kg dose level, and ataxia at the 5.0 g/kg dose level. Gross necropsy revealed dark liver and kidney in 3, and enlarged kidney in 4 rats at the 1.31 g/kg dose level; red intestine in 1 and blood in the bladder in all rats at the 2.56 g/kg dose level; blood in the bladder in all rats at the 5.0 g/kg dose level.
[Olin Corp.; Report on Acute Dermal Toxicity in Rabbits, (1976), EPA Doc. No. 86-890000171, Fiche. No. OTS0516708] **UNREVIEWED**Acute oral toxicity was evaluated using 5 groups of 5 Charles River COBS male rats administered ethlyene glycol mono-n-butyl ether by gavage (dose levels not reported). Mortality occurred within 14 days after dosing, but the LD50 value was not reported. Clinical observations included inactivity, labored breathing, rapid respiration, anorexia, slight to moderate weakness, tremors and prostration. Gross necropsy of animals dying within 14 days of dosing revealed bloody urine, and blood in the stomach and intestine. These conditions were not observed in animals surviving through 14 days.
[Eastman Kodak Co.; Comparative Toxicity of Nine Glycol Ethers: I. Acute Oral LD50, (1981), EPA Doc. No. 86-890000206, Fiche No. OTS0516743] **UNREVIEWED**Acute oral toxicity was evaluated using 5 groups of 5 Charles River COBS CD-1 male mice administered ethlyene glycol mono-n-butyl ether by gavage (dose levels not reported). Mortality occurred within 14 days after dosing, but the LD50 value was not reported. Clinical observations included inactivity, labored breathing, rapid respiration, anorexia, slight to moderate weakness, tremors and prostration. Gross necropsy of animals dying within 14 days of dosing revealed bloody urine and blood in the stomach and intestines. These conditions were not observed in animals surviving through 14 days.
[Eastman Kodak Co.; Comparative Toxicity of Nine Glycol Ethers: I. Acute Oral LD50, (1981), EPA Doc. No. 86-890000206, Fiche No. OTS0516743] **UNREVIEWED**Acute oral toxicity was evaluated using 5 groups of 5 Charles River COBS male rats administered ethlyene glycol mono-n-butyl ether by gavage (dose levels not reported). Mortality occurred within 14 days after dosing, but the LD50 value was not reported. Clinical observations included inactivity, labored breathing, rapid respiration, anorexia, slight to moderate weakness, tremors and prostration. Gross necropsy of animals dying within 14 days of dosing revealed bloody urine, and blood in the stomach and intestine. These conditions were not observed in animals surviving through 14 days.
[Eastman Kodak Co.; Comparative Toxicity of Nine Glycol Ethers: I. Acute Oral LD50, (1981), EPA Doc. No. 86-890000210, Fiche No. OTS0516747] **UNREVIEWED**Acute oral toxicity was evaluated using 5 groups of 5 Charles River COBS CD-1 male mice administered ethlyene glycol mono-n-butyl ether by gavage (dose levels not reported). Mortality occurred within 14 days after dosing, but the LD50 value was not reported. Clinical observations included inactivity, labored breathing, rapid respiration, anorexia, slight to moderate weakness, tremors and prostration. Gross necropsy of animals dying within 14 days of dosing revealed bloody urine and blood in the stomach and intestines. These conditions were not observed in animals surviving through 14 days.
[Eastman Kodak Co.; Comparative Toxicity of Nine Glycol Ethers: I. Acute Oral LD50, (1981), EPA Doc. No. 86-890000210, Fiche No. OTS0516747] **UNREVIEWED**Acute oral toxicity was evaluated in groups of male and female Sherman rats (total number not reported) administered single doses of a 10% water dilution of butyl Cellosolve (ethylene glycol mono-n-butyl ether) by gavage (number of dose levels not reported). Mortality was observed within 14 days of dosing. The oral LD50 value for males was calculated (using Thompson's method) to be 2.9 g/kg, and for females, 2.3 g/kg. Clinical observations included sluggishness, rough coat, prostration and narcosis. Gross necropsy revealed congested or hemorrhagic lungs, mottled liver, congested kidneys and bloody urine.
[Union Carbide Corp.; Butyl Cellosolve: I. Acute and Subacute Toxicity, (1984), EPA Doc. No. 86-890000263, Fiche No. OTS0516797] **UNREVIEWED**Acute oral toxicity was evaluated in groups of 5 rats (sex and strain not reported) administered single doses (method of administration not reported) of ethylene glycol n-butyl ester ether at dose levels of 0.252, 0.5, and 1.0 g/kg. Mortality was observed within 4 days of dosing in 3 animals at 0.5 g/kg and 2 at 1.0 mg/kg; the LD50 was 0.47 g/kg. Clinical observations included drowsiness and blood in the urine. Gross necropsy findings were not reported.
[Dow Chem Co,; Results of Rang Finding Toxicological Tests on Dowanol EB (sanitized), (1959), EPA Doc. No. 86-890001175S, Fiche No. OTS0520315] **UNREVIEWED**Acute oral toxicity was evaluated in groups of 5 male Wistar rats administered single doses of butyl oxide by oral gavage at dose levels of 1.25, 2.50, 5.0, and 10.0 ml/kg of body weight. Mortality was observed within 1 day of dosing in 2 animals of the 2.50 ml/kg group, and in 5 rats of each of the 5.0 and 10.0 ml/kg groups; the LD50 was 2.68 ml/kg of body weight. Clinical observations included bloody saliva, sluggishness, difficult breathing and an unsteady gait. Gross necropsy revealed dark livers, stomach distention, red kidneys and adrenals, and blood was found in the intestines.
[Bushy Run Research Ctr.; Butyl Cellosolve Range Finding Toxicity Studies with Attachments and Cover Sheet and Letter Dated 060689, (1980), EPA Doc. 86-890000938, Fiche No. OTS0520376] **UNREVIEWED**Acute oral toxicity was evaluated in 5 groups of 3 female CDF Fischer-344 rats receiving ethylene glycol mono-n-butyl ether by oral gavage at dose levels of 130, 250, 300, 500, 1000, or 2000 mg/kg. Mortality was observed at the 2 highest dose levels. The oral LD50 ranged from 1000 and 2000 mg/kg. Clinical observations included staining of perineal region, rough hair coat, lethargy, rapid shallow breathing and palpebral closure. Gross necropsy findings were not reported.
[Dow Chemical Co.; Dowanol EB Crude: Acute Toxicological Properties and Industrial Handling Hazards With Attachment, (1981), EPA Doc. 86-890001225, Fiche No. OTS0520735] **UNREVIEWED**Acute dermal toxicity was evaluated in 4 groups of 4 New Zealand white rabbits (sex not reported) administered single doses of PolySolv EB (ethylene glycol mono-n-butyl ether) on clipped and abraded skin at dose levels of 0.25, 0.5, 1.0 and 2.0 g/kg. Mortalities were observed winthin 14 days of dosing in 0/4 rabbits at dose level 0.25 g/kg, 1/4 rabbits at the 0.5 g/kg dose level, and all animals at the two highest dose levels. The Litchfield and Wilcoxon LD50 was calculated to be 0.58 g/kg with 95% confidence limits of 0.31 and 0.85 g/kg. Clinical observations include blood in the urine, yellow cornea, flaccidity, lacrimation and anorexia. Gross necropsy revealed blood in the bladder, as well as discolored liver, kidney and intestines.
[Olin Corp.; Report on Acute Dermal Toxicity in Rabbits, (1976), EPA Doc. No. 86-890000171, Fiche. No. OTS0516708] **UNREVIEWED**Acute dermal toxicity was evaluated in rabbits (number, sex distribution and strain not reported) administered single doses (dose levels not reported) of 2-butoxyethanol by open application. The LD50 was 2.0 mL/kg (specific mortalities, clinical observations and gross necropsy not reported).
[Eastman Kodak Co.; Material Safety Data Sheet, Environmental Safety Data Sheet, and Acute Oral LD50 for 2-Butoxyethanol with Cover Letter Dated 04/19/89, (1988), EPA Doc. No. 86890000198, Fiche No. OTS0516735] **UNREVIEWED**Acute dermal toxicity was evaluated in rabbits (sex and strain not reported) receiving dermal applications of ethylene glycol mono-n-butyl ether at dose levels of 0.2 g/kg (group of 10) or 0.252 g/kg (group of 4). Mortality was observed within 2 to 7 days of dosing in 4 animals of the 0.252 g/kg group. No mortalities were observed at the 0.2 g/kg dose level. A dermal LD50 was not reported. Clinical observations included slight initial weight loss and slight to moderate irritation of the skin at both dose levels. Gross necropsy results were not reported.
[Dow Chem Co,; Results of Range Finding Toxicological Tests on Dowanol EB (sanitized), (1959), EPA Doc. No. 86-890001175S, Fiche No. OTS0520315] **UNREVIEWED**Acute dermal toxicity was evaluated in groups of 4 male New Zealand white rabbits receiving single applications of butyl oxide to clipped intact skin of the trunk at dose levels of 0.5 and 1.0 ml/kg body weight. Mortality was observed within 1 to 2 days of dosing in 1 animal of the 0.5 ml/kg group and in all animals exposed to 1.0 ml/kg body weight. The LD50 was 0.630 ml/kg body weight (95% confidence limit = 0.386 to 1.03 ml/kg). Erythema and necrosis were noted in the high dose groups. Gross necropsy revealed included blood in the urine, orange-red colored lungs and livers, dark colored spleens, dark red kidneys, orange colored peritoneal and intestines.
[Bushy Run Research Ctr.; Butyl Cellosolve Range Finding Toxicity Studies with Attachments and Cover Sheet and Letter Dated 060689, (1980), EPA Doc. 86-890000938, Fiche No. OTS0520376] **UNREVIEWED**An acute inhalation toxicity study was conducted with groups of male and female albino Wistar rats (3/sex/group) receiving whole body exposure to the vapors of ethylene glycol monobutyl ether in a dynamic air flow chamber. The vapor was generated in a glass flask containing the test substance maintained at 20 +/- 1 degrees celsius. Maximum exposure was for 7 hours, but if deaths occurred during either the exposure period or observation period, exposures were repeated at shorter intervals. During the 7 hour exposure, no animals died, but 3 females and 1 male animals died between day 1 and day 3 of the 14 day observation period. Therefore the test was repeated, and two additional test were performed at exposure times of 1 and 3 hours. No deaths were reported for the 1 hour group rats and only one 3 hour exposed female animal died on the day 1 of the observation period. Post exposure observations were lethargy (7 & 3 hour group rats), blood in urine (all exposures), piloerection (7 & 3 hour), paleness of eyes and feet (all exposures) and necrosis at the ends of the tail (7 hour). Seven hour group males appeared to recover by day 11; 3 hour males by day 1 and females by days 6-8; and 1 hour males by day 1 and females by day 2. The theoretical saturated concentration of ethylene glycol monobutyl ether at 20 degrees celsius was calculated to be 617ppm and the concentrations by weight loss estimation were calculated to be 769, 771 and 828ppm for the 7, 3 and 1 hour exposure, respectively.
[Shell Toxicology Laboratory (Tunstall); Test Standardization: Inhalation Toxicity testing of 8 Chemical According to the OECD Inhalation Hazard Test, (1982), EPA Document No. 878212113, Fiche No. OTS0205969 ] **UNREVIEWED**Acute 7-hour inhalation toxicity of different industrial formulations of ethylene glycol monobutyl ether (Dowanol EB, n-butyl oxitol - USA (BO-USA), and n-butyl oxitol - Europe (BO-Europe) was evaluated in 3 groups of 4 male albino rabbits (strain not reported) exposed to the nominal concentration of 410 ppm. A fourth group served as negative control. A 1-week observation period followed exposure. The number dead or moribund by group were 3, 1, and 4 in the Dowanol EB, BO-USA, and BO-Europe groups, respectively. Clinical signs reported were poor coordination and loss of equilibrium. Changes in body weight and necropsy results were not reported.
[Dow Chem Co.; Inhalation Toxicity Studies on Three Samples of Ethylene Glycol Monobutyl Ether (No Date), EPA Document No. 86-890001224, Fiche No. OTS0520734] **UNREVIEWED**Acute 7-hour inhalation toxicity of different industrial formulations of ethylene glycol monobutyl ether (Dowanol EB, n-butyl oxitol - USA (BO-USA), and n-butyl oxitol - Europe (BO-Europe) was evaluated in 3 groups of 2 male beagle dogs exposed to the nominal concentration of 410 ppm. A fourth group served as negative control. A 1-week observation period followed exposure. No dogs died. The only clinical sign reported was salivation during exposure. No body weight changes are mentioned. No animals were sacrificed for necropsy.
[Dow Chem Co.; Inhalation Toxicity Studies on Three Samples of Ethylene Glycol Monobutyl Ether (No Date), EPA Document No. 86-890001224, Fiche No. OTS0520734] **UNREVIEWED**Acute 7-hour inhalation toxicity of different industrial formulations of ethylene glycol monobutyl ether (Dowanol EB, n-butyl oxitol - USA (BO-USA), and n-butyl oxitol - Europe (BO-Europe) was evaluated in 3 groups of 8 male guinea pigs (strain not reported) exposed to 410 ppm (nominal). A fourth group served as negative control. A 1-week observation period followed exposure. No mortalities were observed. Clinical signs, changes in body weight, and necropsy results are not reported.
[Dow Chem Co.; Inhalation Toxicity Studies on Three Samples of Ethylene Glycol Monobutyl Ether (No Date), EPA Document No. 86-890001224, Fiche No. OTS0520734] **UNREVIEWED**Acute toxicity was evaluated in groups of 4 female Sprague-Dawley rats receiving a single intraperitoneal injection of n-butyl Oxidol or Dowanol EB Glycol Ether (ethylene glycol monobutyl ether) at dose levels of 200, 252, 316, or 398 mg/kg bw, then observed for two weeks. The LD50 was 252-317 mg/kg bw. All treated rats had bloody urine and nasal porphryin secretion; those treated with the two higher doses of n-butyl Oxidol also displayed tremors. Surviving rats gained weight throughout the recovery period. The authors concluded that both types of ethylene glycol monobutyl ether have similar toxicity when injected intraperitoneally in rats.
[Dow Chemical Company; Toxicity Studies of N-Butyl Oxide and Dowanol EB Glycol Ether, (1972), EPA Document No. 86-890001223, Fiche No. OTS0520733] **UNREVIEWED**The effects of ethylene glycol butyl ether (EGBE) at concentration of 0.05, 0.1, 0.25, 0.4, and 0.5% on in vitro human erythrocyte fragility was evaluated employing 0.68% sodium chloride and 37 degrees C incubation. Hemolytic activity was reported to be 1.5, 20.5 and 70.9% at EGBE concentrations of 0.25, 0.4 and 0.5% respectively. This activity was compared to the hemolysis activity of rat, rabbit and dog erythrocytes under the same conditions. Rat hemolytic activity was reported to be 2.5, 51.5 and 62.0% and rabbit activity was 2.8, 83.7, and 72.0% at EGBE concentrations of 0.25, 0.4 and 0.5% respectively. Dog hemolytic activity was 46.8, 36.2, 41.2 and 62.3% at EGBE concentrations of 0.05, 0.1, 0.4, and 0.5% respectively.
[Imperial Chemical Industries PLC Central Toxicology Laboratory; Ethylene Glycol Butyl Ether and Butoxyacetic acid: Their Effects on Erythrocyte Fragility in Four Species, (1985), EPA Document No. 40-8578134, Fiche No. OTS0512447] **UNREVIEWED**Subchronic toxicity was evaluated in groups of 10 male Charles River COBS albino rats receiving once daily oral gavage doses of undiluted ethylene glycol monobutyl ether at dose levels of 222, 443, or 885 mg/kg body weight/day, 5 days a week for 6 weeks. Mortality was observed in 2 high dose group rats and 1 middle dose group rat during the treatment period. Clinical observations included lethargy, and red discolored urine. A dose dependent decrease in body weight gain observed throughout the treatment period was only statistically significant (ANOVA, p < 0.05) at the high dose level. Effects on hematological parameters included a dose dependent decrease in hemoglobin concentration, red blood cell count, and mean corpuscular hemoglobin concentrations (MCHC); hemoglobin concentrations and red blood cell counts were reduced (p < 0.05) at all doses, while MCHC was lower (p < 0.05) than control at the middle and high dose levels. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) showed a dose-dependent increase which was significant (p < 0.05) at all levels for MCH and at the middle and high dose levels for MCV. Slight but significant (p < 0.05) increases were seen in serum glutamic pyruvic transaminase in the high dose group, and alkaline phosphatase was significantly increased in the middle and high dose groups. Relative liver weights were increased (p < 0.05) at all dose levels, while relative weights of the kidneys, heart, brain and spleen were increased in the middle and high dose groups. Gross necropsy examination revealed darkened, enlarged spleens in the middle and high dose groups. Treatment related histopathology included hepatocytomegaly (in the high dose group); focal hemosiderin in livers (high and mid groups); and hyalin droplet degeneration, splenic congestion, minor hemosiderin accumulation in the proximal convoluted tubules of the kidney, hyperkeratosis and acanthosis in the stomach (in all groups).
[Eastman Kodak Company Toxicology Section; The Subchronic Oral Toxicity of Ethylene Glycol Monobutyl Ether in Male Rats, EPA Document No. 88-8300509, Fiche No. OTS0503697] **UNREVIEWED**Subchronic oral toxicity was evaluated in 4 groups of 10 male rats (strain not reported) administered ethylene glycol monobutyl ether by gavage at dose levels of 0, 222, 443 and 885 mg/kg/day for 5 days/week over 6 weeks. Mortalities included 2 rats at the 885 mg/kg/day dose level and 1 rat at the 443 mg/kg/day level. Clinical observations included lethargy at the 443 and 885 mg/kg/day treatment levels, as well as rough coat and piloerection at the 885 mg/kg/day dose level. A dose-related weight reduction was observed, but reduced food consumption was significant (statistical test and significance level not reported) only at the 885 mg/kg/day dose level. Dose-related decreases in red blood cell count and in hemoglobin concentration were observed. Elevated liver weights, increased serum alkaline phosphatase concentration (443, 885 mg/kg/day) and increased serum glutamic pyruvic transaminase concentration (885 mg/kg/day) were observed. Serum glucose was reduced in rats at the 885 mg/kg/day treatment level. Gross necropsy revealed enlarged dark spleens at the 443 and 885 mg/kg/day treatment levels. Histopathological evaluation revealed hepatocytomegally and focal hemosiderin in the liver at the two highest dose levels, as well as hemosiderin in the kidney, splenic congestion, and hyperkeratosis and acanthosis in the stomach at all dose levels. Urinalysis was not reported.
[Eastman Kodak Co.; The Subchronic Oral Toxicity of Ethylene Glycol Monobutyl Ether in Male Rats; (1983); EPA Doc. No. 86-890000196, Fiche No. OTS0516733] **UNREVIEWED**Subchronic oral toxicity was evaluated in 3 groups of 10 male albino Charles River rats administered diethylene glycol monomethyl ether by gavage at dose levels equivalent to 1/2, 1/4 and 1/8 of the acute LD50 (actual dose levels not reported) 5 days/week for 6 weeks. An additional group of 10 untreated rats was used as a negative control. Compound-related mortality was not observed. The only clinical sign of toxicity was bloody urine and blood around the nares in one rat at the highest dose level. Significant (p < 0.05) weight loss was observed only in rats at the highest treatment level. No treatment-related hematological or clinical biochemistry effects were reported. Reduction in relative testis weight was observed in rats at the highest dose level. Gross necropsy revealed no abnormalities in treated rats, but histopathologic examination revealed testicular atrophy.
[Eastman Kodak Co.; Comparative Toxicity of Nine Glycol Ethers: Six Weeks Repeated Dose Study; (1986); EPA Doc. No. 86-890000196, Fiche No. OTS0516733] **UNREVIEWED**Subchronic toxicity was evaluated in groups of 10 male albino rats (CR, COBS, CD, BR) given doses of ethylene glycol mono-n-butyl ether equivalent to 0, 1/2, 1/4 or 1/8 of the acute oral LD50 for the test compound in rats (more specific information regarding doses was not reported), by oral gavage, 5 days/week for six weeks. No effect was noted on mortality. Food consumption and body weights were reduced only in rats from the high-dose group. Dose-related effects were seen on hematological parameters, but not serum chemistry. Relative spleen weights increased in rats from the mid- and high-dose groups, liver weights increased in rats from the high-dose group and smaller than normal thymuses were observed in two rats from the high-dose group. Rats given mid- or high-dose levels had bloody urine, lethargy, unkempt hair coats, piloerection, rales, slight weakness and inactivity. Diffuse hemorrhage of the thymus was observed in one high-dose rat. Rats given the test compound (response to specific dose levels was not reported) had hepatocytomegally, anisokaryosis, and lack of cytoplasmic basophilia in livers, and congestion and extramedullary hematopoiesis in spleens.
[Eastman Kodak Company; Comparative Toxicology of Nine Glycol Ethers: III. Six Weeks Repeated Dose Study, (1966), EPA Document No. 86-890000206, Fiche No. OTS0516743] **UNREVIEWED**Subchronic toxicity was evaluated in groups of 10 male albino rats (CR, COBS, CD, BR) given doses of ethylene glycol mono-n-butyl ether equivalent to 0, 1/2, 1/4 or 1/8 of the acute oral LD50 for the test compound in rats (more specific information regarding doses was not reported), by oral gavage, 5 days/week for six weeks. No effect was noted on mortality. Food consumption and body weights were reduced only in rats from the high-dose group. Mean hemoglobin concentration and total erythrocyte count were reduced, and mean corpuscular hemoglobin was increased, in rats from all treatment groups. Rats from the mid- and high-dose groups had increased in mean corpuscular volume and decreased mean corpuscular hemoglobin concentration. Treatment did not alter serum chemistry. Relative spleen weights increased in rats from the mid- and high-dose groups, and liver weights increased and smaller than normal thymuses were observed in rats from the high-dose group. Rats given mid- or high-dose levels had bloody urine, lethargy, unkempt hair coats, piloerection, rales, slight weakness and inactivity. Diffuse hemorrhage of the thymus was observed in one high-dose animal. Rats given the test compound (response to specific dose levels was not reported) had hepatocytomegally, anisokaryosis, and lack of cytoplasmic basophilia in livers, and congestion and extramedullary hematopoiesis in spleens.
[Eastman Kodak Company; Comparative Toxicology of Nine Glycol Ethers: III. Six Weeks Repeated Dose Study, (1966), EPA Document No. 86-890000206, Fiche No. OTS0516743] **UNREVIEWED**Subchronic dermal toxicity was evaluated in groups of 20 New Zealand White rabbits (10 male and 10 female) receiving occluded applications of ethylene glycol monobutyl ether at doses of 10, 50 or 150 mg/kg body weight, 5 days/week for 13 weeks. Mortality was observed in 1 low dose group female, 1 mid dose and 1 high dose group male during the treatment period. Clinical observations included red feces, red liquid material on cage lining, anorexia, congestion, nasal discharge, and emaciation. Slight to moderate erythema and edema, along with scaling and flaking were observed at the treatment site. Treatment related changes in food consumption, body weights, or organ to body weight ratios were not observed at any dose level. Additionally, the test article did not induce changes in hematology, or in serum chemistry parameters. Treatment related pathological effects were not observed on gross or microscopic examination of the adrenals, aorta bone, brain, epidymis, esophagus, eyes, gall bladder, heart, intestines, kidneys, liver, lung, lymph node, mammary gland, ovaries, pancreas, parathyroids, pituitary, prostate, sciatic nerve, seminal vesicles, skeletal muscle, spleen, stomach, submandibular salivary gland, testes, thyroids, thymus, tongue, trachea, urinary bladder, uterus, or vagina.
[WIL Research Laboratories, Inc.; 90-Day Subchronic Dermal Toxicity Study in Rabbits with Ethylene Glycol Monobutyl Ether (1983), EPA Document No. FYI-AX-0683-0178SU, Fiche No. OTS0000178-1] **UNREVIEWED**Subchronic toxicity was evaluated in 3 female and 3 male New Zealand White rabbits exposed to unoccluded doses of diethylene glycol butyl ether as a 1.5% solution in distilled water at a level of 2.0 mg/kg/day for 28 days. There were no mortalities. Clinical observations included slight dermal reaction. Necropsy revealed compound-related abberations in none of the treated animals.
[Proctor and Gamble; Information on Diethylene Glycol (Mono) Butyl Ether (DGBE) Diethylene Glycol with Cover Letter Dated 052284, (1984), EPA Doc No 40-8478029, Fiche No OTS0512397] **UNREVIEWED**Subchronic dermal toxicity was evaluated in 5 groups of 10 New Zealand White rabbits (1:1 sex ratio/group) exposed dermally under occlusive patches to 2-butoxyethanol at nominal dose levels of 0, 0.02, 0.1, 0.2, and 0.4 ml/kg for 6 hours/day, on 9 of 11 consecutive days. Residual test compound was removed with absorbant material, but not washed off, after each exposure. Animals were sacrificed after a 14-day observation period. No treatment-related mortality or ophthalmologic effects were observed. Dose-related progressive erythema, edema, and necrosis were observed at the site of application. Both hemoglobinuria and proteinuria were observed at the 2 highest dose levels, and both were reversible after cessation of dosing. Both reduced red blood cell count and a decrease over time of urinary hemoglobin were observed in the highest dose group. No treatment-related changes were observed in clinical chemistry, body weight, organ weight, or histopathologic data. A gross thickening of the skin at the site of treatment was observed.
[Bushy Run Res. Ctr.; Butyl Cellosolve 9-day Dermal Application to Rabbits (1980), EPA Document No. 86-890000168, Fiche No. OTS0516705] **UNREVIEWED**Subchronic dermal toxicity was evaluated in 4 groups of 20 New Zealand White rabbits (1:1 sex ratio per group) dermally exposed to 0, 10, 50, and 150 mg/kg, respectively. Rabbits were dosed under an occlusive dressing for 6 hours/day, 5 days/week, over a 90-day period. It was not reported whether the site of application was washed after each 6-hour dosing. No treatment-related changes in mortality, clinical signs, food consumption rate, body weight, hematological parameters, serum chemistry, organ weights, gross pathological parameters, or histopathological parameters were observed.
[WIL Research Laboratories, Inc.; 90-Day Subchronic Dermal Toxicity Study in Rabbits with Ethylene Glycol Monobutyl Ether (1983), EPA Document No. 86-890000237, Fiche No. OTS0516772] **UNREVIEWED**Subchronic dermal toxicity was evaluated in groups of 5 male and 5 female New Zealand White rabbits receiving daily dermal (occluded) applications of 1 ml/day of 0, 5, 25, 50, or 100% concentrations of butyl CELLOSOLVE for a total of 9 applications over an 11-day period. There were no treatment-related mortalities. Clinical observations included dermal irritation (necrosis, edema, and erythema). Females in the 100% (undiluted) butyl CELLOSOLVE group displayed significantly reduced (p < 0.05) body weights. Hematological examination revealed significant (p < 0.05) reductions in the mean erythrocyte counts, hemoglobin, and mean corpuscular hemoglobin concentrations and increased mean corpuscular hemoglobin in females administered the undiluted material. Urinalysis revealed hemoglobin in the urine (males at 100%), increased urinary protein levels (males and females at 100%), and the presence of blood (females at 50 and 100%). Clinical biochemical anlaysis was not reported. Gross necropsy findings included thickening of the skin of males at 100%. There were no treatment-related organ/body weight changes. Histopathological examination of the kidneys revealed interstitial nephritis and tubular changes in rabbits exposed to the undiluted material.
[Bushy Run Research Center; Butyl Cellosolve 9-Day Repeated Dermal Application to Rabbits with Attachments, Cover Sheet and Letter Dated 06/06/89, (1980), EPA Doc. No. 86-890000947, Fiche No. OTS0520385] **UNREVIEWED**Subchronic inhalation toxicity was evaluated in 4 groups of Fischer 344 rats exposed by inhalation to ethylene glycol monomethyl ether (butyl CELLOSOLVE) at air concentrations of 0 ppm (15 female, 16 male), 20 ppm (8 female, 8 male), 86 ppm (8 female, 8 male), and 245 ppm (15 female, 16 male), respectively, for 6 hours/day for 9 days. Rats were sacrificed either shortly after the final exposure or after a 14-day observation period. No mortalities were observed. Audible respiration, nasal discharge, and red-stained urine were seen in the highest exposure group. Transient body weight gain decreases occurred in the 2 highest exposure groups. Increases were observed in the 245 ppm group in mean corpuscular volume, nucleated red cells, reticulocytes and lymphocytes (males only), and decreases were seen in erythrocyte count, hemoglobin, and mean corpuscular hemoglobin concentration. Groups exposed to 86 ppm showed an increase in mean corpuscular volume and a decrease in hemoglobin. After the 14-day observation period, only the leukocyte count recovered to control levels. The mean liver/body weight ratio was elevated in females and males of the 2 highest and in the highest exposure groups, respectively. The incidence of gross lesions was not treatment-related. Evaluations of treatment effects on urinalysis, clinical chemistry, and histopathology were not reported.
[Bushy Run Res. Ctr.; Butyl Cellosolve 9-Day Vapor Inhalation Study on Rats (1981), EPA Document No. 86-890000169, Fiche No. OTS0516706] **UNREVIEWED**Subchronic inhalation toxicity was evaluated in 4 groups of 32 Fischer 344 rats (1:1 sex ratio per group) exposed by inhalation to ethylene glycol monomethyl ether (butyl CELLOSOLVE) at air concentrations of 0, 5, 25, and 77 ppm for 6 hours/day, 5 days/week over 13 weeks. An interim sacrifice of 6 rats of each sex was executed after 30 exposures. No treatment-related effects were observed in male rats at any exposure level, with respect to mortality, clinical signs (via the Irwin Screen Test), mean body weight, food consumption rate, clinical chemistry, urinalysis, hematology, gross necropsy, and histopathology. Females in the highest exposure group exhibited a transitory depression of weight gain in the first weeks of exposure, as well as minimal reductions in red blood cell count, hemoglobin, and hematocrit. No other treatment-related effects were observed in the females.
[Bushy Run Res. Ctr.; Butyl Cellosolve Rat 90-Day Inhalation Study (1981), EPA Document No. 86-890000170, Fiche No. OTS0516707] **UNREVIEWED**Hemolysis was evaluated in vitro with human erythrocytes (suspended in veronal buffered isotonic saline) exposed to ethylene glycol butyl ether (EGBE) for 1 hour. The percent hemolysis for 0.1, 0.25, 0.4, or 0.5% EGBE was 0, 1.5, 20.5, and 70.9%, respectively.
[Central Toxicology Lab; Ethylene Glycol Butyl Ether and Butoxyacetic Acid: Their Effects on Erythrocyte Fragility in Four Species, (not reported), EPA Document No. 86-8900000727, Fiche No. OTS0521233] **UNREVIEWED**Hemolysis was evaluated in vitro with rat erythrocytes (suspended in veronal buffered isotonic saline) exposed to ethylene glycol butyl ether (EGBE) for 1 hour. The percent hemolysis for 0.1, 0.25, 0.3, 0.4, and 0.5% EGBE was 0, 2.5, 0, 51.5, and 62%, respectively.
[Central Toxicology Lab; Ethylene Glycol Butyl Ether and Butoxyacetic Acid: Their Effects on Erythrocyte Fragility in Four Species, (not reported), EPA Document No. 86-8900000727, Fiche No. OTS0521233] **UNREVIEWED**Hemolysis was evaluated in vitro with dog erythrocytes (suspended in veronal buffered isotonic saline) exposed to ethylene glycol butyl ether (EGBE) for 1 hour. The percent hemolysis for 0.05, 0.1, 0.4, and 0.5% EGBE was 46.8, 36.2, 41.2, and 62.3%, respectively.
[Central Toxicology Lab; Ethylene Glycol Butyl Ether and Butoxyacetic Acid: Their Effects on Erythrocyte Fragility in Four Species, (not reported), EPA Document No. 86-8900000727, Fiche No. OTS0521233] **UNREVIEWED**Hemolysis was evaluated in vitro with rabbit erythrocytes (suspended in veronal buffered isotonic saline) exposed to ethylene glycol butyl ether (EGBE) for 1 hour. The percent hemolysis for 0.1, 0.25, 0.4, or 0.5% EGBE was 0, 2.8, 83.7, and 72.0%, respectively.
[Central Toxicology Lab; Ethylene Glycol Butyl Ether and Butoxyacetic Acid: Their Effects on Erythrocyte Fragility in Four Species, (not reported), EPA Document No. 86-8900000727, Fiche No. OTS0521233] **UNREVIEWED**In an absorption study, the permeability of human abdominal skin to 2-butoxyethanol was measured in vitro using Franz-type glass diffusion cells. Epidermal layers from human skin were exposed for 8 hours to a solution containing radiolabeled test compound in the donor chamber and the appearance of radioactivity was measured in the receptor chamber. Damage to skin was calculated by comparing the water absorption rates of skin before and after exposure to the test compound. The rate of absorption of the test compound across human skin was 0.20 mg/cm2/hr. Exposure to the test chemical did not alter the permeability of skin to water.
[Central Toxicology Lab; 2-butylethanol, 2-ethoxyethanol, 2-ethoxyethyl acetate, 2-methoxyethanol, and 1-methoxypropan-2-ol: Absorption Through Human Skin In Vitro, (1982), EPA Document No. 86-890000943; Fiche No. OTS0520381] **UNREVIEWED**In an absorption study, the permeability of human abdominal skin to 2-butoxyethanol was measured in vitro using Franz-type glass diffusion cells. Epidermal layers from human skin were exposed for 8 hours to a solution containing radiolabeled test compound in the donor chamber and the appearance of radioactivity was measured in the receptor chamber. Damage to skin was calculated by comparing the water absorption rates of skin before and after exposure to the test compound. The rate of absorption of the test compound across human skin was 0.20 mg/cm2/hr. Exposure to the test chemical did not alter the permeability of skin to water.
[Central Toxicology Lab; Glycol ethers (2-methoxyethanol, 2-ethoxyethanol, 2-butoxyethanol, 2-ethoxyethyl acetate, and 1-methoxypropan-2-ol: Relationships Between Human Skin Absorption and Inhaled Doses, (1982), EPA Document No. 86-890000944; Fiche No. OTS0520382] **UNREVIEWED**Metabolism of Dowanol EB (ethylene glycol mono-n-butyl ether) was evaluated in vitro with an equine liver alcohol dehydrogenase assay obtained from the Sigma Chemical Company. The Vmax, Km, and Vmax/Km were 4.06, 1.18X10E-3, and 3.50, respectively. The authors concluded that alcohol dehydrogenase has a high affinity for the test compound, indicating that the test compound is probably metabolized to a significant extent by this enzyme in vivo.
[Dow Chemical Company; In Vitro Studies to Evaluate Glycol Ethers as Substrates for Alcohol Dehydrogenase, (1982), EPA Document No. 86-890001231S, Fiche No. OTS0520741] **UNREVIEWED**Ethylene glycol monobutyl ether (CAS# 111-76-2) was studied for reproductive effects in 50 CD-1 mice when administered by oral gavage for 8 days at 1180 mg/kg/day on gestation days 7 through 14. Observations continued through day 3 postpartum. The dose was selected based on the results of a preliminary maximum tolerated dose test on groups of 10 nonpregnant, female CD-1 mice using doses of 295, 590, 1180, 2365, and 4275 mg/kg administered by oral gavage for 8 days. A water (vehicle) control group was used. The test group included 11 deaths, of which 5 were of pregnant mice, 7 resorbed pregnancies and 24 live births. Chi-square testing showed significant difference (p<0.01) from the control in the reproductive index (number of females bearing viable litters per number ofpregnant females). ANOVA testing indicated that a trend toward decreased maternal weight and maternal weight changes were not significant and there were no significant changes in litter sizes and litter weight changes between day 1 and day 3 postpartum.
[Bioassay Systems Corporation; Determination of the Reproductive Effects in Mice of Nine Selected Chemicals (1983), EPA Document No. FYI-OTS-0483-0240, Fiche No. OTS0000240-0] **UNREVIEWED**Ethylene glycol monobutyl ether (CAS# 111-76-2) was studied for reproductive effects in 50 CD-1 mice when administered by oral gavage for 8 days at 1180 mg/kg/day on gestation days 7 through 14. Observations continued through day 3 postpartum. The dose was selected based on the results of a preliminary maximum tolerated dose test on groups of 10 nonpregnant, female CD-1 mice using doses of 295, 590, 1180, 2365, and 4275 mg/kg/day administered by oral gavage for 8 days. A water (vehicle) control group was used. The test group included 11 deaths of which 5 were of pregnant mice, 7 resorbed pregnancies and 24 live births. Chi-square testing showed significant difference (p<0.01) from the control in the reproductive index (number of females bearing viable litters per number of pregnant females). ANOVA testing indicated that a trend toward decreased maternal weight and maternal weight changes were not significant and there were no significant changes in litter sizes and litter weight changes between day 1 and day 3 postpartum.
[Bioassay Systems Corporation; Determination of the Reproductive Effects in Mice of Nine Selected Chemicals (1983), EPA Document No. 40-8336210, Fiche No. OTS0506158] **UNREVIEWED**A one-generation reproductive toxicity study was conducted with groups of 25 male and 25 female Charles River COBS CD rats administered diethylene glycol butyl ether (DGBE) in deionized water by gavage at a level of 250, 500 or 1000 mg/kg/day. Three groups of males were dosed 60 days prior to mating through to sacrifice and 3 groups of females were dosed 14 days prior to mating, continuing until sacrifice or weaning. Control animals received the vehicle only at a level of 5 ml/kg/day. Treated animals were mated with untreated counterparts and about one-half of the females in each group underwent uterine examinations on gestation day 13. Observations of the treated F0 animals and their offspring included the following: mortality observed in 2 low-dose females, 1 mid-dose male and female and 3 high-dose males and females; excess salivation in high-dose females; reduced body weights in high- dose males; reduction in mean pup body weight during latter stages of lactation in the offspring of high-dose females; and reduction in the mean numbers of uterine implants in high-dose females and females paired with high-dose males.
[Procter & Gamble; Information on Diethylene Glycol (Mono) Butyl Ether (DGBE) Diethylene Glycol with Cover Letter Dated 052284, (1984), EPA Doc No 40- 8478029, Fiche No OTS0512397] **UNREVIEWED**Teratogenicity was evaluated in groups of 6 pregnant CD-1 mice administered ethylene glycol monobutyl ether by oral gavage at doses of 0, 350, 600, 1000, 1500, and 2000 mg/kg on days 8-14 of gestation. Surviving animals were sacrificed on gestation day 18. Maternal mortality was observed in 3 mice at 1500 mg/kg and in all 6 at 2000 mg/kg. Significant reductions in maternal body weights were observed at 1000 and 2000 mg/kg. Clinical signs of maternal toxicity included green-brown or red-brown staining of papers beneath the cages of animals at treatment levels 600 mg/kg and above, while at 1500 and 2000 mg/kg, animals exhibited vaginal discharge, lethargy, abnormal breathing, and the inability of several animals to right themselves. Gross necropsy revealed distention and enlargement of gall bladders (350, 600, 1000 and 1500 mg/kg), enlargement of the spleen (350, 1500 and 2000 mg/kg), and distention of the stomach and intestinal tract (1500 & 2000 mg/kg). Significant changes between dose groups and controls were observed for total resorptions (increased at 1000 and 1500 mg/kg), resorptions/implantation (increased at 1500 mg/kg), and live fetuses/implantation (decreased at 1500 mg/kg). A dose-related increase in resorptions and dead fetuses and decrease in live fetuses was observed. Cleft palates were observed in 4/43 fetuses at 1000 mg/kg and in 1/25 at 1500 mg/kg.
[Exxon Chem Co; Teratology Probe Study I and II in Mice and Reproduction Study in Mice, (1985), EPA Doc. No. 89-890000248, Fiche No. OTS0516782] **UNREVIEWED**Reproductive toxicity was evaluated in groups of 10 pregnant Charles River CD female mice receiving an oral gavage dose of ethylene glycol mono-n-butyl ether at 10 ml/kg body weight on gestation days 7 through 14. Maternal mortality was approximatedly 8% in the test group. Clinical observations and gross necropsy results were not reported. There was a significant reduction (p<0.05) in the number of live pups per litter, reduced survival, and reduced birth weight among offspring of treated dams.
[Department of Health & Human Services; Results of Testing Fifteen Glycol Ethers in a Short-Term In Vivo Reproductive Toxicity Assay With Attachments, EPA Doc. 40-8385037, Fiche No. OTS0521552] **UNREVIEWED**Teratogenicity was evaluated in mated Fischer 344 rats (30/group) exposed by inhalation to ethylene glycol mono-butyl ether (EGBE) at nominal concentrations (number of pregnant rats) of 0 (21), 100 (21), 200 (16) or 300 (24) ppm on gestation days (GD) 6-15 for 6 hrs/day. The rats were sacrificed on GD 21. There were significant differences observed between pregnant treated and control animals in the following: decreased maternal body weight gain and decrease in food consumption (all treated groups during exposure), increased food consumption (200 and 300 ppm groups, post-exposure), decreased water consumption (200 and 300 ppm, exposure period), decreased uterine and liver absolute weights (300 ppm), increased non-viable implantations and percent pre-implantation loss and decreased viable implantations and percent live implantations (300 ppm), increased incidence of ventricular septal defect, and absent and severely shortened innominate artery (300 ppm). There were no significant differences observed between pregnant treated and control animals in the following: post-exposure water consumption, weights of thymus and spleen, relative weights of uterus and liver, numbers of corpora lutea, and total implantations.
[Bushy Run Research Center, Union Carbide Corp.; Inhalation Teratological Potential of Ethylene Glycol Monobutyl Ether in the Rat. (1983), EPA Document No. 88-8300481, Fiche No. OTS0503697] **UNREVIEWED**Teratogenicity was evaluated in pregnant Fischer 344 rats (36/group) exposed by inhalation to ethylene glycol mono-butyl ether (EGBE) at nominal concentrations of 0, 25, 50, 100 or 200 ppm on gestation days (GD) 6-15. The rats were sacrificed on GD 21. There were significant differences observed between treated and control animals in the following: increase in number of totally resorbed litters (200 ppm group), increased incidence of clinical observations including cold and pale extremities, abnormal tails, fur and urogenital areas stained, urogenital wetness and encrustation, occult blood (200 ppm), periocular wetness and perinasal encrustation (100 and 200 ppm), decreased body weight (200 ppm), decreased body weight gain (100 and 200 ppm, exposure period, 200 ppm post-exposure period also), decreased food consumption (100 and 200 ppm, exposure period), increased water consumption (100 ppm, post-exposure), decreased gravid uterine weight and increased relative and absolute spleen and relative kidney weights (200 ppm), decreased red blood cell count and mean corpuscular hemoglobin volume and increased mean corpuscular volume and corpuscular hemoglobin level (100 and 200 ppm), increased hemoglobin and hematocrit levels (200 ppm), decreased viable implants and percent live fetuses and increased non-viable implants and embryonic resorptions (200 ppm), increased number of litters with 1 or more cases of unossified skeletal elements (100 and 200 ppm) including anterior arch of the atlas and cervical centra, cervical arches, sternebrae, and proximal phalanges (200 ppm), unossified cervical centrum (100 ppm), and decreased incidence of bilobed cervical centrum 5 (100 and 200 ppm). There were no significant differences observed between treated and control animals in the following: pregnancy rates, early deliveries, dead fetuses, liver and thymus and absolute kidney weights, numbers of corpora lutea, total implants, dead fetuses, pre-implantation loss, fetal sex ratio, mean litter weight, external, visceral, skeletal or total malformations.
[Bushy Run Research Center, Union Carbide Corp.; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. 88-8400598, Fiche No. OTS0503697] **UNREVIEWED**Teratogenicity was evaluated in pregnant New Zealand white rabbits (24/group) exposed by inhalation to ethylene glycol mono-butyl ether (EGBE) at nominal concentrations of 0, 25, 50, 100 or 200 ppm on gestation days (GD) 6-18. The rats were sacrificed on GD 29. There were significant differences observed between treated and control animals in the following: decreased maternal body weight (200 ppm group on GD 15), increased hemoglobin and hematocrit levels (100 ppm group), decreased gravid uterine weight (200 ppm), reduced number of total implants and viable implants/litter (200 ppm), increased number of litters with fusion of papillary muscles in left ventricle (100 ppm), and reduced ossification of sternebra 6 and rudimentary rib (200 ppm). There were no significant differences observed between treated and control animals in the following: maternal mortality, number of spontaneous abortions, pregnancy rates, maternal body weight gain, number of non-viable implants, pre-implantation losses, percent live fetuses, sex ratio, fetal body weights/litter, and number of fetuses or of litters with one or more affected fetuses with pooled external, visceral, skeletal or total malformations.
[Bushy Run Research Center, Union Carbide Corp.; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 Rats and New Zealand White Rabbits Following Inhalation Exposure. (1984), EPA Document No. 88-8400598, Fiche No. OTS0503697] **UNREVIEWED**An inhalation toxicity study was conducted with groups of 36 mated female F-344 rats exposed to ethylene glycol mono-n-butyl ether at target concentrations (analytical concentrations) of 25 (25), 50 (50), 100 (98), 200 (201), ppm on gestation days (GD) 6-15 for 6 hrs/day. The animals were sacrificed on GD 21. Mortality was not observed. Clinical observations included hematuria, urogenital discharge, red urogenital wetness and encrustations, pale and cold extremities, and necrosis of the tail tip. Maternal toxicity was evident in the high-exposure group by significant changes (p<0.001) in body weight, body weight gain, gravid uterine weight, and food and water consumption. Absolute and relative spleen weights and relative kidney weights were also increased relative to controls in this group. Toxicity related hematologic observations included significant reductions in erythrocyte count, significant increases in hemoglobin and hematocrit, significant enlargement of red blood cells, increase in hemoglobin per cell, and significant reduction in mean corpuscular hemoglobin concentration. Evidence of maternal toxicity in the 100 ppm dose group included significant changes in the following: weight gain, food consumption, size of red blood cells, and mean corpuscular hemoglobin concentration. Embryotoxicity was indicated in the 200 ppm dose group by a significant increase in number of totally resorbed litters (p<0.01), a significant decrease in number of viable implantations per litter (p<0.001) and a significant decrease in percent of live fetuses (p<0.01). A reduction in skeletal ossification was also observed in these groups. There were no statistically significant increases in the incidence of external, visceral, skeletal, or total malformations in any treatment group relative to controls.
[Bushy Run Research Center; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 & New Zealand White Rabbits Following Inhalation Exposure (Final Report) with Cover Letter, (1984), EPA Document No. 40-8478020, Fiche No. OTS0512387] **UNREVIEWED**An inhalation toxicity was conducted with groups 24 pregnant New Zealand white rabbits of exposed to ethylene glycol mono-n-butyl ether at target concentrations, (analytical concentration) of 25 (25), 50 (50), 100 (98), 200 (201), ppm on gestation days (GD) 6-18 for 6 hrs/day. The animals were sacrificed on GD 29. Mortality was observed in 4 dams in the high-exposure group; however, a significant difference from controls was not observed. Clinical observations included periocular wetness, perinasal wetness and discharge, red fluid on tray, and stained fur. Significantly decreased (p<0.05) maternal body weight, and gravid uterine weight, and increased number of abortions (4) were observed in the high dose group. A significant reduction (p<0.05) in the number of total implants and viable implants per litter were observed at the high-exposure level. There were no significant effects on the number of non-viable implants, preimplantation loss, percent live fetuses, sex ratio, or fetal body weight per litter. A significant increase (p<0.05, Fisher's Exact Test) was observed in unossified sternebra 6 and in the rudimentary rib lumbar 1, bilateraly. No statistically significant increases in the incidence of malformations was observed in any treatment group relative to controls.
[Bushy Run Research Center; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 & New Zealand White Rabbits Following Inhalation Exposure (Final Report) with Cover Letter, (1984), EPA Document No. 40-8478020, Fiche No. OTS0512387] **UNREVIEWED**Teratogenicity was evaluated in groups of 36 pregnant Fischer 344 rats exposed to ethylene glycol monobutyl ether vapors at concentrations of 0, 25, 50, 100, and 200 ppm for 6 hours/day on days 6-15 of gestation. Maternal mortality was not observed and all rats were sacrificed on gestation day 21. Clinical signs of maternal toxicity at 100 and 200 ppm included red straining and wetness of the fur, fluid on trays beneath cages, periocular wetness, and perinasal encrustation. Additional clinical observations at 200 ppm included cold and pale extremities, discoloration and ulceration of the tail tip, and absence of the tail tip. A significant (p<0.001, Bonferroni t-test) reduction in maternal body weights was observed at 200 ppm, as was the rate of food consumption at 100 and 200 ppm. Hematologic findings included significantly (p<0.001) reduced hemoglobin and hematocrit values at 200 ppm and red blood cell counts at 100 and 200 ppm. Gross necropsy of dams revealed a significant (p<0.001) reduction in relative spleen weights. Examination of the uteri revealed significant (p<0.01) reductions in the numbers of viable implants and resorptions and the percent of live fetuses at 200 ppm. The numbers of corpora lutea, total implants and preimplantation losses and the sex ration were not effected by the material at any concentration. There were no significant differences between control and exposure groups with respect to the incidence of external, visceral, skeletal, or total fetal malformations.
[Jefferson Chem Co., Inc.; Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 Rats and New Zeland White Rabbits Following Inhalation Exposure, (1984), EPA Doc. No. 86-890000237, Fiche No. OTS0516772] **UNREVIEWED**Teratogenicity was evaluated in groups of 24 pregnant New Zeland white rabbits exposed to ethylene glycol monobutyl ether vapors at concentrations of 0, 25, 50, 100, and 200 ppm for 6 hours/day on days 6-18 of gestation. Maternal mortality was observed in 4 rabbits at 200 ppm; all surviving rabbits were sacrificed on gestation day 29 and the uteri examined. Clinical signs of maternal toxicity at 100 and 200 ppm included periocular wetness and red fluid on the trays beneath the cages. Additional clinical observations at 200 ppm included staining of the fur and perinasal wetness and discharge. There were no differences between control and treatment groups with respect to maternal body weights, hematological findings, the number of non-viable implants, preimplantation losses, percent live fetuses, sex ratios, or fetal weights. Significant (p<0.05) reductions in uterine weights and the number of total and viable implants/litter were observed at 200 ppm. The incidence of external, visceral, skeletal, and total fetal malformations at all exposure levels was not significantly different from that of the control group.
[Jefferson Chem Co., Inc.; Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 Rats and New Zeland White Rabbits Following Inhalation Exposure, (1984), EPA Doc. No. 86-890000237, Fiche No. OTS0516772] **UNREVIEWED**Developmental toxicity was evaluated in groups of 36 female Fischer 344 rats receiving whole-body exposure to ethylene glycol monobutyl ether at vapor concentrations of 0, 25, 50, 100, or 200 ppm, for 6 hours/day, on gestation days 6-15, followed by fetal examination on gestation day 21. Maternal toxicity was observed at the two highest dose levels, including clinical signs, reduced body weight gain, food consumption, and gravid uterine weight, and increased relative spleen and kidney weight. The compound was embryotoxic (increased incidence of resorptions) and fetotoxic (reduced skeletal ossification) at the two highest dose levels, but the incidence of fetal malformations was unchanged at all dose levels. The NOEL was estimated at 50 ppm.
[Bushy Run Research Center; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 rats and New Zealand White Rabbits Following Inhalation Exposure, (1984), EPA Document No. 86-890001527, Fiche No. OTS0529656] **UNREVIEWED**Developmental toxicity was evaluated in groups of 24 female New Zealand white rabbits receiving whole-body exposure to ethylene glycol monobutyl ether at vapor concentrations of 0, 25, 50, 100, or 200 ppm, for 6 hours/day, on gestation days 6-18, followed by fetal examination on gestation day 29. Maternal toxicity was observed at the highest dose level, including clinical signs, reduced body weight gain and gravid uterine weight, and increased incidence of mortality and abortion. The compound was embryotoxic (reduced number of viable fetuses) at the highest dose level, but no treatment-related effects were noted with respect to fetotoxicity or fetal malformations. The NOEL was estimated at 100 ppm.
[Bushy Run Research Center; A Teratologic Evaluation of Ethylene Glycol Monobutyl Ether in Fischer 344 rats and New Zealand White Rabbits Following Inhalation Exposure, (1984), EPA Document No. 86-890001527, Fiche No. OTS0529656] **UNREVIEWED**Developmental toxicity was evaluated in groups of pregnant rabbits exposed to ethylene glycol monoethyl ether acetate at vapor concentrations of 0, 25, 100, and 400 ppm. Maternal body weight gain and food consumption decreased in the high-dose group. Decreased body weight and retarded skeletal ossification were observed in fetuses from the mid- and high-dose groups; the high dose was also embryotoxic (increased resorptions) and teratogenic (major malformations of the vertebral column). The document summarized this study, and no further information was available regarding experimental methods or results.
[Chemical Manufacturers Association; Glycol Ethers Program Panel Research Status Report, (1983), EPA Document No. 86-890001473S, Fiche No. OTS0521087] **UNREVIEWED**Developmental toxicity was evaluated in groups of pregnant rats (strain and number per group not reported) exposed to ethylene glycol monobutyl ether at vapor concentrations of 0, 100, 200, or 300 ppm. Maternal toxicity was observed at all dose levels and some fetal effects were noted (not specified). The document summarized this study, and no further information was available regarding experimental methods or results.
[Chemical Manufacturers Association; Glycol Ethers Program Panel Research Status Report, (1983), EPA Document No. 86-890001473S, Fiche No. OTS0521087] **UNREVIEWED**Ethylene glycol monobutyl ether (CAS# 111-76-2) was evaluated for developmental toxicity. It was administered in 24 pregnant New Zealand white rabbits exposed to 0, 25, 50, 100 or 200 ppm of the test material on days 6-18 of gestation. Maternal weight gains were not significantly altered by treatment. At 200 ppm maternal toxicity was observed, including apparent exposure-related increases in deaths and abortions, clinical signs (periocular wetness, perinasal wetness and discharge), decreased weight during gestation day 15 (p < 0.05) and reduced gravid uterine weight (p < 0.05) at sacrifice. Embryotoxicity was exhibited by a reduced number of total and viable implantations (p < 0.05) per litter. No treatment-related fetotoxicity was observed. No treatment-related increases in fetal malformations or variations were seen at any exposure level. At 200 ppm ethylene glycol monobutyl ether exhibited maternal and embryo toxicity, but no fetotoxicity or teratogenicity.
[SHELL OIL CO; A teratologic evaluation of ethylene glycol monobutyl ether in Fischer 344 rats & New Zealand white rabbits following inhalation exposure; 2/27/84, EPA 88-920002161, Fiche No. OTS0539224] **UNREVIEWED**Ethylene glycol monobutyl ether (CAS# 111-76-2) was evaluated for developmental toxicity. It was administered in 24 pregnant New Zealand white rabbits at exposure levels of 0, 25, 50, 100 or 200 ppm of the test material on days 6-18 of gestation. Maternal weight gains were not significantly altered by treatment. At 200 ppm maternal toxicity was observed, including apparent exposure-related increases in deaths and abortions, clinical signs (periocular wetness, perinasal wetness and discharge), decreased weight during gestation day 15 (p < 0.05) and reduced gravid uterine weight (p < 0.05) at sacrifice. Embryotoxicity was exhibited by a reduced number of total and viable implantations (p < 0.05) per litter. No treatment-related fetotoxicity was observed. No treatment-related increases in fetal malformations or variations were seen at any exposure level. At 200 ppm ethylene glycol monobutyl ether exhibited maternal and embryo toxicity, but no fetotoxicity or teratogenicity.
[SHELL OIL CO; A teratologic evaluation of ethylene glycol monobutyl ether in Fischer 344 rats & New Zealand white rabbits following inhalation exposure; 2/27/84, EPA 88-920002161, Fiche No. OTS0539224] **UNREVIEWED**Ethylene glycol monobutyl ether (CAS# 111-76-2) was evaluated for developmental toxicity. It was administerd in 36 pregnant Fischer 344 rats per group exposed to 0, 25, 50, 100, or 200 ppm of ethylene glycol monobutyl ether on days 6-15 of gestation. Maternal toxicity was expressed as significant reductions in body weight (p < 0.001) at 200 ppm, weight gain (p < 0.05) during exposure at 100 and 200 ppm, food consumption (p < 0.001) at 100 and 200 ppm, and the presence of hematuria. Embryofetal toxicity included increased numbers of resorbed litters (p < 0.01), decreased numbers of viable implants (p < 0.001), decreased percent of live fetuses (p < 0.01) and delayed ossification (p < 0.05). No statistically significant increases in the incidence of external, visceral, skeletal, or total malformations were observed. At 25 ppm or less there was no maternal, embryo or fetal toxicity. Inhalation exposure to 100 ppm or above of ethylene glycol monobutyl ether caused maternal toxicity, embryotoxicity, and fetotoxicity, but no teratogenicity.
[DOW CHEM CO; A teratologic evaluation of ethylene glycol monobutyl ether in Fischer 344 rats & New Zealand white rabbits following inhalation exposure; 2/27/84, EPA 88-920005150, Fiche No. OTS0544124] **UNREVIEWED**Ethylene glycol monobutyl ether (CAS# 111-76-2) was evaluated for developmental toxicity. It was administered in 24 pregnant New Zealand white rabbits exposed to 0, 25, 50, 100 or 200 ppm of ethylene glycol monobutyl ether on days 6-18 of gestation. Maternal weight gains were not significantly altered by treatment. At 200 ppm maternal toxicity was observed, including apparent exposure-related increases in deaths and abortions, clinical signs (periocular wetness, perinasal wetness and discharge), decreased weight during gestation day 15 (p < 0.05) and reduced gravid uterine weight (p < 0.05) at sacrifice. Embryotoxicity was exhibited by a reduced number of total and viable implantations (p < 0.05) per litter. No treatment related fetotoxicity, increases in fetal malformations, or variations were seen at any exposure level. At 200 ppm ethylene glycol monobutyl ether exhibited maternal and embryo toxicity, but no fetotoxicity or teratogenicity.
[DOW CHEM CO; A teratologic evaluation of ethylene glycol monobutyl ether in Fischer 344 rats & New Zealand white rabbits following inhalation exposure; 2/27/84, EPA 88-920005150, Fiche No. OTS0544124] **UNREVIEWED**The ability of 2-butoxyethanol to induce mutations at the gene locus coding for hypoxanthine-guanine phosphoribosyl transferase in Chinese hamster ovary cells (CHO/HGPRT Assay) was evaluated in both the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity tests, nonactivated cultures were treated with 0.0625, 0.125, 0.25, 0.5 or 1.0% butyl cellosolve (v/v) and produced a range of 138.6 to 95.6 relative growth. S9-activated cultures treated with 0.03125, 0.0625, 0.125, 0.25, or 0.5% produced a range of 137 to 84.7% relative growth. None of the culture produced mutant frequencies significantly greater than the solvent control.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery, (1980), EPA Doc. No. 86-890000167, Fiche No. OTS0516704] **UNREVIEWED**The frequency of sister chromatid exchange (SCE) was determined in Chinese hamster ovary cells exposed in vitro to butyl cellosolve with and without metabolic activation provided by Aroclor-induced rat liver S9 fraction. The test article was administered at concentrations of 0.00780, 0.01560, 0.03125, 0.625, 0.125, and 0.25% butyl cellosolve (v/v) both in the presence and absence of metabolic activation. A statistically significant (p < 0.05) increase in SCE's/cell and SCE's/chromosome was not observed in any of the cultures at any concentration.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery, (1980), EPA Doc. No. 86-890000167, Fiche No. OTS0516704] **UNREVIEWED**The effects of 2-butoxyethanol were examined in the rat hepatocyte primary culture/DNA repair assay. Based on preliminary toxicity tests, 2-butoxyethanol was tested at concentrations of 0.0001, 0.001, 0.003, 0.01, 0.03, and 0.1% v/v. None of the tested concentrations caused a significant increase in unscheduled DNA synthesis over the solvent (DMSO) control.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery, (1980), EPA Doc. No. 86-890000167, Fiche No. OTS0516704] **UNREVIEWED**The ability of 2-butoxyethanol to induce mutations at the gene locus coding for hypoxanthine-guanine phosphoribosyl transferase in Chinese hamster ovary cells (CHO/HGPRT Assay) was evaluated in both the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity tests, nonactivated cultures were treated with 0.0625, 0.125, 0.25, 0.5 or 1.0% butyl cellosolve (v/v) and produced a range of 138.6 to 95.6 relative growth. S9-activated cultures treated with 0.03125, 0.0625, 0.125, 0.25, or 0.5% produced a range of 137 to 84.7% relative growth. None of the culture produced mutant frequencies significantly greater than the solvent control.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery, (1980), EPA Doc. No. 86-890000167, Fiche No. OTS0516704] **UNREVIEWED**The effects of 2-butoxyethanol were examined in the rat hepatocyte primary culture/DNA repair assay. Based on preliminary toxicity tests, 2-butoxyethanol was tested at concentrations of 0.0001, 0.001, 0.003, 0.01, 0.03, and 0.1% v/v. None of the tested concentrations caused a significant increase in unscheduled DNA synthesis over the solvent (DMSO) control.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery, (1980), EPA Doc. No. 86-890000167, Fiche No. OTS0516704] **UNREVIEWED**The frequency of sister chromatid exchange (SCE) was determined in Chinese hamster ovary cells exposed in vitro to butyl cellosolve with and without metabolic activation provided by Aroclor-induced rat liver S9 fraction. The test article was administered at concentrations of 0.00780, 0.01560, 0.03125, 0.625, 0.125, and 0.25% butyl cellosolve (v/v) both in the presence and absence of metabolic activation. A statistically significant (p < 0.05) increase in SCE's/cell and SCE's/chromosome was not observed in any of the cultures at any concentration.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery, (1980), EPA Doc. No. 86-890000167, Fiche No. OTS0516704] **UNREVIEWED**[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery with Attachments, Cover Sheets and Letter Dated 06/06/89. (1980). EPA Document No. 86-890000946, Fiche No. OTS0520384} In an in vitro sister chromatid exchange assay, chinese hamster ovary cells (CHO-K1-BH4-D1) were exposed to 0.0, 0.0156, 0.03125, 0.0625, 0.125, 0.25% ethylene glycol mono-n-butyl ether, with or without an S-9 metabolic activating system from Arochlor 1254 induced rat liver. Doses were selected based on low cytotoxicity to CHO cells in a preliminary study. No treatment-related effects were seen, either in the presence or absence of a metabolic activating system.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery with Attachments, Cover Sheets and Letter Dated 06/06/89. (1980). EPA Document No. 86-890000946, Fiche No. OTS0520384} The ability of butyl cellosolve to induce specific mutations at the gene locus coding for hypoxanthine-guanine phosphoribosyl transferase in Chinese hamster ovary cells (CHO/HGPRT Assay) was evaluated in presence and absence of metabolic activation from Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity tests, non-S9 activated cultures were treated with 0.0625, 0.125, 0.25, 0.5, or 1.0% v/v, and the S9 activated cultures were treated with 0.03125, 0.0625, 0.125, 0.25, or 0.5% v/v. None of the cultures had mutant frequencies significantly greater than the solvent (H2O) control.
In an in vitro DNA repair assay, hepatocytes from Hilltop-Wistar albino rats were exposed for 2 hours to 0.0001, 0.001, 0.003, 0.01, 0.03, and 0.1% ethyl glycol mono-n-butyl ether, dissolved in DMSO. No metabolic activating system was used. The concentrations used were non-cytotoxic to rat hepatocytes. The level of unscheduled DNA synthesis was determined by measuring the incorporation of 3H-thymidine into cell nuclei DNA or into precipitated DNA, using a liquid scintillation counter. Statistically significant increases in the level of unscheduled DNA synthesis were observed at the two lowest dose-levels, but not at the four highest dose-levels.
[Bushy Run Research Center; Butyl Cellosolve In Vitro Mutagenesis Studies: 3-Test Battery with Attachments, Cover Sheets and Letter Dated 06/06/89. (1980). EPA Document No. 86-890000946, Fiche No. OTS0520384] **UNREVIEWED**The mutagenicity of butyl cellosolve (ethylene glycol mono-n-butyl ether) was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537, and TA1538 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on the results of preliminary bacterial toxicity testing, the material was tested for mutagenicity at concentrations of 0, 2000, 4000, 6000, 8000, 10000, and 15000 ug/plate using the direct plate incorporation method. Butyl cellosolve did not cause a reproducible positive response in any of the bacterial tester strains, either in the presence or absence of added metabolic activation.
[Haskell Laboratories; Mutagenic Activity of Butyl Cellosolve in the Salmonella/Microsome Assay with Attachments and Cover Sheet Dated 06/12/89 (Sanitized), (1977), EPA Doc. No. 86-890000829S, Fiche No. OTS0520963] **UNREVIEWED**Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
... METABOLIZED, @ LEAST IN PART, TO BUTOXYACETIC ACID ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3933]**PEER REVIEWED**Seventeen persons who were exposed to glycolethers in a varnish production plant, were examined according to their external and internal solvent exposure. The workers in the production plant (n= 12) were exposed to average concentrations of ethoxyethanol, ethoxyethyl acetate, butoxyethanol, 1-methoxypropanol-2, 2-methoxypropyl-1-acetate and xylene of 2.8; 2.7; 1.1; 7.0; 2.8 and 1.7 ppm. Internal exposure was estimated by measuring butoxyethanol in blood as well as ethoxyacetic acid and butoxyacetic acid in urine samples. As expected, the highest values were found in the varnish production. The average post shift concentrations of butoxyethanol, ethoxyacetic acid and butoxyacetic acid were 121.3 ug/l; 167.8 and 10.5 mg/l. The relatively high concentrations of ethoxyacetic acid and butoxyacetic acid in pre-shift samples can be explained by the long half-lives of these metabolites. Most of the glycolethers were taken up through the skin. The authors think that a future tolerable limit value for the concentration of ethoxyacetic acid in urine should be in the order of 100 to 200 mg/l.
[Angerer J et al; Int Arch Occup Environ Health 62 (2): 123-6 (1990)]**PEER REVIEWED**The elimination kinetics of 2-butoxyethanol (ethylene glycol monobutyl ether) were studied in the once-through isolated perfused rat liver system in the presence and absence of ethanol. Dose-dependent Michaelis-Menten kinetics in the elimination of ethylene glycol monobutyl ether were observed. The apparent Michaelis constant range from 0.32 to 0.70 mM while the maximum elimination rate ranged from 0.63 to 1.4 umol/min/g liver. In the presence of 17.1 mM ethanol (0.1%) the extraction ratio of ethylene glycol monobutyl ether decreased from 0.44 to 0.11. Ethylene glycol monobutyl ether is mainly metabolized via oxidation by alcohol dehydrogenase in the rat liver.
[Johanson G et al; Toxicol Appl Pharmacol 83 (2): 315-20 (1986)]**PEER REVIEWED**For the glycol ethers 2-methoxyethanol, 2-ethoxyethanol, and 2-butoxyethanol, the effect of alkyl group length on disposition of these three glycol ethers was studied in male F344/N rats allowed access for 24 hr to 2-butoxy(U-(14)C)ethanol, 2-ethoxy (U-(14)C)ethanol, or 2-methoxy(U-(14)C)ethanol in drinking water at three doses (180 to 2590 ppm), resulting in absorbed doses ranging from 100 to 1450 umols/kg body weight. The majority of the (14)C was excreted in urine or exhaled as carbon dioxide. Less than 5% of the dose was exhaled as unmetabolized glycol ether. Distinct differences in the metabolism of the glycol ethers as a function of alkyl chain length were noted. For 2-butoxyethanol 50-60% of the dose was eliminated in the urine as butoxyacetic acid and 8-10% as carbon dioxide; for 2-ethoxyethanol 25-40% was eliminated as ethoxyacetic acid and 20% as carbon dioxide; for 2-methoxyethanol 34% was eliminated as methoxyacetic acid and 10-30% as carbon dioxide. Ethylene glycol, a previously unreported metabolite of these glycol ethers, was excreted in urine, representing approximately 10, 18, and 21% of the dose for 2-butoxyethanol, 2-ethoxyethanol, and 2-methoxyethanol, respectively. Thus, for longer alkyl chain lengths, a smaller fraction of the administered glycol ether was metabolized to ethylene glycol and carbon dioxide. Formation of ethylene glycol suggests that dealkylation of the glycol ethers occurs prior to oxidation to alkoxyacetic acid and, as such, represents an alternate pathway in the metabolism of these compounds that does not involve formation of the toxic acid metabolite.
[Medinsky MA et al; Toxicol Appl Pharmacol 102 (3): 443-55 (1990)]**PEER REVIEWED**Ethylene glycol monobutyl ether was rapidly absorbed in male rats after gavage administration, metabolized, and eliminated. Tissue distribution of ethylene glycol monobutyl ether revealed that ethylene glycol monobutyl ether is distributed to all tissues with the highest levels (detected 48 hr after dosing) detected in the forestomach followed by the liver, kidney, spleen, and the glandular stomach. However, the increase in the tissue concn in rats treated with 500 mg/kg (as compared to that in rats treated with 125 mg/kg ethylene glycol monobutyl ether) was not proportional to the increase in ethylene glycol monobutyl ether dose. The major route of ethylene glycol monobutyl ether elimination was in the urine, followed by (14)CO2 exhalation. The portion of the ethylene glycol monobutyl ether dose eliminated in urine or as (14)CO2 was significantly higher in rats treated with 125 mg/kg than in the rats treated with 500 mg/kg. This indicates that saturation of ethylene glycol monobutyl ether-metabolizing enzymes occurs at the high dose. A small portion (8%) of the administered dose (500 mg/kg) was excreted in the bile in 8 hr after dosing. The major urinary metabolite, butoxyacetic acid, accounted for >75% of the radioactivity excreted in the urine. The 2nd major metabolite in urine was the glucuronide conjugate of ethylene glycol monobutyl ether. In the bile, the major biliary metabolite was BEG followed by butoxyacetic acid. A small quantity of the radioactivity excreted in the urine of rats treated with the low dose of ethylene glycol monobutyl ether was the sulfate conjugate of ethylene glycol monobutyl ether; however, no BES was detected in the urine of rats treated with the high dose of ethylene glycol monobutyl ether. The following metabolic pathways of ethylene glycol monobutyl ether are identified: oxidation of ethylene glycol monobutyl ether to butoxyacetic acid, conjugation of ethylene glycol monobutyl ether with uridine diphosphate glucuronic acid, and conjugation of ethylene glycol monobutyl ether with the sulfate.
[Ghanayene BI et al; Metab Dispos 15 (4): 478-84 (1987)]**PEER REVIEWED**Absorption, Distribution & Excretion:
... ABSORBED VIA SKIN, LUNG, OR GASTROINTESTINAL TRACT.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 301]**PEER REVIEWED**... BUTOXYACETIC ACID ... IS EXCRETED IN URINE OF MOST ANIMAL SPECIES & OF HUMAN BEINGS. ANIMAL TESTS ALSO INDICATE THAT ETHYLENE GLYCOL BUTYL ETHER IS EXCRETED VIA THE LUNG.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3933]**PEER REVIEWED**THEY FOUND 55 MG OF BUTOXYACETIC ACID IN 16 HR URINE SAMPLES OF DOGS EXPOSED TO 385 PPM. ... 100 & 42 MG IN 24-HR URINE SAMPLES FROM 2 DOGS EXPOSED TO 200 PPM OF VAPOR & 100 & 94 MG IN SIMILAR URINE SAMPLES FROM 2 DOGS EXPOSED TO 100 PPM. ONE OF TWO MONKEYS EXPOSED TO 100 PPM EXCRETED 30 MG ... IN 48-HR PERIOD ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3938]**PEER REVIEWED**HUMAN BEINGS EXPOSED 8 HR TO 195 PPM EXCRETED ANYWHERE FROM 6-300 MG BUTOXYACETIC ACID IN 24 HR PERIOD.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3938]**PEER REVIEWED**... ONCE ABSORBED INTO BODY, ESTERS ARE SAPONIFIED & SYSTEMIC EFFECT IS QUITE TYPICAL OF PARENT GLYCOL OR GLYCOL ETHER. /ETHER-ESTERS OF GLYCOLS/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 4010]**PEER REVIEWED**The percutaneous absorption of 2-butoxyethanol (Butyl cellosolve) was investigated in 5 men. The presence of butoxyethanol in blood and of butoxyacetic acid in urine confirmed that butoxyethanol enters the systemic circulation in man in vivo during dermal exposure. Calculated percutaneous uptake rates ranged from 7 to 96 nmol/min/sq cm. Persons exposing large portions of their skin to butoxyethanol are at risk of absorbing acutely toxic doses.
[Johanson G et al; Scandinavian Journal of Work, Environ and Health 14 (2): 101-9 (1988)]**PEER REVIEWED**The absorption across isolated human abdominal epidermis was measured in vitro. Epidermal membranes were set up in glass diffusion cells. 2-Methoxyethanol was most readily absorbed (mean steady rate 2.82 mg/sq cm/hr) was also apparent for 1-methoxypropan-2-ol. There was a trend of reducing absorption rate with increasing molecular weight or reducing volatility for monoethylene glycol ethers (2-methoxyethanol, 2.82 mg/sq cm/hr; 2-ethoxyethanol, 0.796 mg/sq cm/hr; 2-butoxyethanol, 0.198 mg/sq cm/hr) and also within the diethylene glycol series: 2-(2-methoxyethoxy) ethanol, (0.206 mg/sq cm/hr); 2-(2-ethoxyethoxy) ethanol, (0.125 mg/sq cm/hr) and 2-(2-butoxyethoxy) ethanol, (0.035 mg/sq cm/hr). The rate of absorption of 2-ethoxyethyl acetate was similar to that of the parent alcohol, 2-ethoxyethanol. Absorption rates of diethylene glycol ethers were slower than their corresponding monoethylene glycol equivalents.
[Dugard PH et al; Environ Health Perspect 57: 193-7 (1984)]**PEER REVIEWED**Acute exposure to 2-butoxyethanol causes dose- and age-dependent hemolytic anemia in rats. Butoxyacetic acid is the proximate hemolytic agent and inhibition of alcohol or aldehyde dehydrogenases protected rats against 2-butoxyethanol induced hemolytic anemia. The kinetics of (14)C-2-butoxyethanol metabolism and clearance were studied in control adult (3-4 months old) and old (12-13 months old) male F344 and in adult male F344 rats treated with pyrazole, cyanamide or probenecid. The area under the curve, maximum plasma concentration and systemic clearance of 2-butoxyethanol were dose-dependent. In contrast, there was no effect of dose on half-life (T1/2) or volume of distribution of 2-butoxyethanol. There was no age effect on T1/2, volume of distribution, or systemic clearance of 2-butoxyethanol. However, maximum plasma concentration and area under the curve of 2-butoxyethanol increased as a function of age. Inhibition of 2-butoxyethanol metabolism by pretreatment of rats with pyrazole or cyanamide resulted in an increase in the T1/2 and area under the curve of 2-butoxyethanol, whereas it caused a decrease in the systemic clearance. Furthermore, pyrazole had no effect, whereas cyanamide had decreased volume of distribution of 2-butoxyethanol.
[Ghanayem BI et al; J Pharmacol Exp Ther 253 (1): 136-43 (1990)]**PEER REVIEWED**Mechanism of Action:
... Ethylene glycol monobutyl ether, and to a greater extent its metabolite, butoxyacetic acid, both increase the osmotic fragility of the erythrocyte. This action appears to be greatest in the rat, mouse, and rabbit and distinctly less in the guinea pig, dog, rhesus monkey, and human.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3938]**PEER REVIEWED**Pharmacology:
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Ethylene glycol mono-n-butyl ether's production and use as a synthetic intermediate and as a solvent in a variety of applications may result in its release to the environment through various waste streams. If released to soil, ethylene glycol mono-n-butyl ether is expected to have high mobility based on as estimated Koc of 67. Volatilization of ethylene glycol mono-n-butyl ether is not expected to be important from moist soil surfaces but may be important from dry soil surfaces based on an estimated Henry's Law constant of 2X10-8 atm-cu m/mol and a measured vapor pressure of 0.88 mm Hg, respectively. Alcohols and ethers are generally resistant to hydrolysis. Such functional groups do not absorb UV light at environmentally significant wavelengths (>290 nm) and are commonly used as solvents for obtaining UV spectra. Therefore, direct photolysis will not be an important process. According to several biodegradation tests, aerobic degradation of ethylene glycol mono-n-butyl ether should occur rapidly in soil and water. If released to water, ethylene glycol mono-n-butyl ether is not expected to adsorb to suspended solids and sediment given its estimated Koc value. Ethylene glycol mono-n-butyl ether is expected to be essentially non-volatile from water surfaces because of its Henry's Law constant. An estimated BCF value of 2.5 suggests that bioconcentration of ethylene glycol mono-n-butyl ether will be low in aquatic organisms. If released to the atmosphere, ethylene glycol mono-n-butyl ether will exist as a vapor based on its vapor pressure. Vapor-phase ethylene glycol mono-n-butyl ether is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals with an estimated half-life of about 20 hours. Particulate-phase ethylene glycol mono-n-butyl ether may be physically removed from the air by wet deposition. The predominant route of exposure to ethylene glycol mono-n-butyl ether is through dermal adsorption; other routes of exposure include ingestion and inhalation of this compound, particularly from household products. (SRC)
**PEER REVIEWED**Probable Routes of Human Exposure:
The most probable route of human exposure to ethylene glycol mono-n-butyl ether is by inhalation, dermal contact and ingestion. Workplace exposures have been documented(2-6). Drinking water supplies have been shown to contain ethylene glycol mono-n-butyl ether(1).
[(1) Lucas SV; GC/MS Anal of Org in Drinking Water Concentrates and Advanced Treatment Concentrates Vol 1 USEPA-600/1-84-020A (NTIS PB85-128239) p 397 (1984) (2) Lehmann E et al; pp. 31-41 in Safety and Health Aspects of Organic Solvents. Riihimaki V, Ulfvarson U eds Alan R Liss Inc. (1986) (3) Hahn WJ, Werschulz PO; Evaluation of Alternatives to Toxic Organic Paint Strippers. NTIS PB86 219-177/AS USEPA 600/S2-86/063 (1986) (4) Clapp DE et al; Environ Health Perspective 57: 91-5 (1984) (5) Shah JJ, Heyerdahl EK; National Ambient VOC Database Update USEPA 600/3-88/010 (1988) (6) Yasuhara, A et al; Agric Bio Chem 50: 1765-70 (1986)]**PEER REVIEWED**THERE IS ... HAZARD OTHER THAN VAPOR THAT MUST NOT BE OVERLOOKED WHEN HANDLING THIS MATERIAL--THAT OF POSSIBLE ABSORPTION OF TOXIC QUANTITIES THROUGH SKIN, BECAUSE OF LOW VAPOR PRESSURE ... @ ROOM TEMP, HAZARD FROM SKIN ABSORPTION COULD WELL BE GREATER, OR CONTRIBUTE SUBSTANTIALLY TO OVER-ALL HAZARD.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3938]**PEER REVIEWED**FROM INDUST POINT OF VIEW, ONLY ONE CASE OF POSSIBLE SYSTEMIC INJURY WAS THAT OF MAN WHO WAS REPORTED ... AS HAVING HAD TWO ISOLATED ATTACKS OF HEMATURIA, WITH 5 MO INTERVAL. ... HIS EXPOSURE ... INCL BUTYL CARBITOL AS WELL AS BUTYL CELLOSOLVE.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 612]**PEER REVIEWED**OCCUPATIONAL EXPOSURES TO BUTYL CELLOSOLVE, ETHANOL, & XYLENE IN FILAMENT-DRAW DEPARTMENT OF ELECTRICAL RESISTOR MFR FACILITY DID NOT POSE A HEALTH HAZARD.
[GILLES ET AL; US NTIS PB REP; ISS PB-273739 (1976) 16 PP]**PEER REVIEWED**NIOSH (NOES Survey as of 3/28/89) has estimated that 1,680,764 workers are potentially exposed to ethylene glycol mono-n-butyl ether in the USA(1). According to the National Ambient Volatile Organic Compounds (VOCs) Database, the median workplace atmospheric concn of ethylene glycol mono-n-butyl ether is 0.075 ppbV for 14 samples(3). Workers at paint stripping operations that used stripping agents containing ethylene glycol mono-n-butyl ether were exposed to it(2).
[(1) NIOSH; National Occupational Exposure Survey (NOES) (1989) (2) Hahn WJ, Werschulz PO; Evaluation of Alternatives to Toxic Organic Paint Strippers. NTIS PB86 219-177/AS USEPA 600/S2-86/063 (1986) (3) Shah JJ, Heyerdahl EK; National Ambient VOC Database Update USEPA-600/3-88/010 (1988)]**PEER REVIEWED**Personal exposures to atmospheric ethylene glycol mono-n-butyl ether at a specialty chemical production facility in June of 1981 ranged from undetected levels to 0.1 ppm; indoor air concn within the facility were as high as 1.7 ppm(2). A national survey of workplaces in the Federal Republic of Germany showed that workers were exposed to solvents containing ethylene glycol mono-n-butyl ether with a 0.4% frequency of occurrence(1).
[(1) Lehmann E et al; pp 31-41 in Safety and Health Aspects of Organic Solvents. Riihimaki V, Ulfvarson U eds Alan R Liss Inc. (1986) (2) Clapp DE et al; Environ Health Perspective 57: 91-5 (1984)]**PEER REVIEWED**A study initiated in 1983, which surveyed the workplace atmospheres of 336 businesses in Belgium, showed that ethylene glycol mono-n-butyl ether was present in 25 of 94 air samples taken from sites that utilize printing pastes; 10 of 81 samples from where painting took place; 1 of 20 samples from automobile repair shops; and 17 of 67 samples from sites where various materials such as varnishes, sterilization agents and cleaners are employed(1). The geometric mean concn of ethylene glycol mono-n-butyl ether in the air of printing shops was 4.1 mg/cu m with a range of 1.5 to 17.7 mg/cu m; 18.8 mg/cu m with a range of 3.4 to 93.6 mg/cu m for painting areas; 5.9 mg/cu m for car repair shops; and 8.5 mg/cu m with a range of 0.2 to 1775 mg/cu m for various industries(1).
[(1) Veulemans H et al; Am Indust Hyg Assoc J 48: 671-7 (1987)]**PEER REVIEWED**Ethylene glycol mono-n-butyl ether was identified as a volatile emission from used machine cutting oils in an automobile manufacturing facility in Japan(1). Non-occupational exposures may occur among populations with contaminated drinking water supplies(2). Because ethylene glycol mono-n-butyl ether is a component of solvent based building materials such as silicone caulk(3), human exposures may occur at construction sites and areas that have undergone remodelling(SRC).
[(1) Yasuhara A et al; Agric Bio Chem 50: 1765-70 (1986) (2) Lucas SV; GC/MS Anal of Org in Drinking Water Concentrates and Advanced Treatment Concentrates Vol 1 USEPA-600/1-84-020A (NTIS PB85-128239) p 397 (1984) (3) Tichenor BA, Mason MA; JAPCA 38: 264-8 (1988)]**PEER REVIEWED**Exposure of cleaning women and cleaners of cars to ethylene glycol mono-n-butyl ether resulted in urine levels of <0.1-7.33 ppm (time-weighted averages)(1). It was established that the predominant route of exposure to ethylene glycol mono-n-butyl ether was through skin penetration(1). Ethylene glycol mono-n-butyl ether was identified in air from automotive repair shops in Sydney, Australia in 8 out of 70 samples at an average concentration of 2.0 mg/cu m(2).
[(1) Vincent R et al; Appl Occup Environ Hyg 8: 580-6 (1993) (2) Winder C, Turner PJ; Am Occup Hyg 36: 385-94 (1992)]**PEER REVIEWED**Artificial Pollution Sources:
Ethylene glycol mono-n-butyl ether was listed as a volatile organic emission of silicone caulk(4). Ethylene glycol mono-n-butyl ether is also released to the environment via leachate from municipal landfills and hazardous waste site(1-3).
[(1) Stonebreaker RD, Smith AJ; pp 1-10 in Contr Haz Mater Spills, Proc Natl Conf Louisville KY (1980) (2) Dunlap WJ et al; Organic Pollutants contributed to groundwater by a Landfill USEPA-600/9-76-004 p. 96-110 (1976) (3) Dunlap WJ et al; Identif Anal Org Pollut 1: 453-77 (1976) (4) Tichenor BA, Mason MA; JAPCA 38: 264-8 (1988)]**PEER REVIEWED**Ethylene glycol mono-n-butyl ether's production and use in hydraulic fluids(1), as coupling agent for many water-based coatings(2), to make acetate esters as well as phthalate and stearate plasticizers(2), as a coupling agent to stabilize immiscible ingredients in metal cleaners, textile lubricants, cutting oils, and liquid household products(2), as a solvent for nitrocellulose resins, spray lacquers, quick-drying lacquers, varnishes, enamels, dry-cleaning compounds, varnish removers, textile, mutual solvent for "soluble" mineral oils to hold soap in solution and to improve the emulsifying properties(3), vinyl and acrylic paints(4), in aqueous cleaners to solubilize organic surfactants(4), and as a solvent in cosmetics(5) may result in its release to the environment through various waste streams(SRC).
[(1) Browning E; Toxicity and Metabolism of Industrial Solvents. NY,NY: American Elsevier pg 609 (1965) (2) Chemical Products Synopsis: Glycol Ethers (1983) (3) Lewis RJSr; Hawley's Condensed Chemical Dictionary. 12th ed. NY,NY: Van Nostrand Rheinhold Co pg 489 (1993) (4) Billig E; Kirk-Othmer Encycl Chem Technol 4th ed. NY,NY: John Wiley and Sons. Vol 4: 691-700 (1992) (5) Rieger MM; Kirk-Othmer Encycl Chem Technol 4th ed. NY,NY: John Wiley and Sons. Vol 7: 572-619 (1993)]**PEER REVIEWED**Environmental Fate:
TERRESTRIAL FATE: Based on a recommended classification scheme(1), an estimated Koc value of 67(SRC), determined from an experimental log Kow(2) and a recommended regression-derived equation(3), indicates that ethylene glycol mono-n-butyl ether is expected to have high mobility in soil(SRC). Volatilization of ethylene glycol mono-n-butyl ether is not expected to be important from moist soil surfaces(SRC) given an estimated Henry's Law constant of 2X10-8 atm-cu m/mole(SRC), using a recommended regression equation(4). Volatilization may be important from dry soil surfaces(SRC) based on an experimental vapor pressure of 0.88 mm Hg(5). Alcohols and ethers are generally resistant to hydrolysis(6). They do not absorb UV light at environmentally significant wavelengths (>290 nm) and are commonly used as solvents for obtaining UV spectra(3). Therefore, direct photolysis will not be an important process. According to several biodegradation tests, aerobic degradation of ethylene glycol mono-n-butyl ether should occur rapidly in soil(5,7-12).
[(1) Swann RL et al; Res Rev 85: 23 (1983) (2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Profess Ref. Heller SR (consult ed) Washington, DC: Amer Chem Soc pg 25 (1995) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington DC: Amer Chem Soc pp. 4-9 (1990) (4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (5) Dow Chemical Company; The Glycol Ethers Handbook. The Dow Chemical Company, Midland, MI 97 pp (1990) (6) Silverstein RM, Bassler GC; Spectrometric Id Org Cmpd, J Wiley and Sons Inc p. 148-169 (1963) (7) Chemicals Inspection and Testing Institute; Biodegradation and Bioaccumulation Data of Existing Chemicals Based on the CSCL Japan. Japan Chemical Industry Ecology - Toxicology and Information Center. ISBN 4-89074-101-1 (1992) (8) Waggy GT et al; Environ Toxicol Chem 13: 1277-80 (1994) (9) Bridie AL et al; Water Res 13: 627-30 (1979) (10) Price KS et al; J Water Pollut Contr Fed 46: 63-77 (1974) (11) Sasaki S; pp. 283-98 in Aquat Pollutants: Transform & Biolog Effects Hutzinger O et al ed Oxf: Pergamon Press (1978) (12) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981)]**PEER REVIEWED**AQUATIC FATE: Based on a recommended classification scheme(1), an estimated Koc value of 67(SRC), determined from an experimental log Kow(2) and a recommended regression-derived equation(1), indicates that ethylene glycol mono-n-butyl ether is not expected to adsorb to suspended solids and sediment(SRC) in the water. Ethylene glycol mono-n-butyl ether is expected to be essentially non-volatile from water surfaces based on an estimated Henry's Law constant of 2X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). An estimated BCF value of 2.5(1,SRC), from an experimental log Kow(2), suggests that ethylene glycol mono-n-butyl ether bioconcentration in aquatic organisms will be low(SRC), according to a recommended classification scheme(4). Alcohols and ethers are generally resistant to hydrolysis(5). They do not absorb UV light at environmentally significant wavelengths (>290 nm) and are commonly used as solvents for obtaining UV spectra(1). Therefore, direct photolysis will not be an important process. According to several BOD biodegradation tests, aerobic degradation of ethylene glycol mono-n-butyl ether should occur rapidly in water(6-12).
[(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington DC: Amer Chem Soc pp. 4-9, 5-4, 5-10, 15-1 to 15-29 (1990) (2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Professional Reference Book. Heller SR (consult ed) Washington, DC: Amer Chem Soc pg 25 (1995) (3) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (4) Franke C et al; Chemosphere 29: 1501-14 (1994) (5) Silverstein RM, Bassler GC; Spectrometric Id Org Cmpd, J Wiley and Sons Inc p. 148-169 (1963) (6) Chemicals Inspection and Testing Institute; Biodegradation and Bioaccumulation Data of Existing Chemicals Based on the CSCL Japan. Japan Chemical Industry Ecology - Toxicology and Information Center. ISBN 4-89074-101-1 (1992) (7) Dow Chemical Company; The Glycol Ethers Handbook. The Dow Chemical Company, Midland, MI 97 pp (1990) (8) Waggy GT et al; Environ Toxicol Chem 13: 1277-80 (1994) (9) Bridie AL et al; Water Res 13: 627-30 (1979) (10) Price KS et al; J Water Pollut Contr Fed 46: 63-77 (1974) (11) Sasaki S; pp. 283-98 in Aquat Pollutants: Transform & Biolog Effects Hutzinger O et al ed Oxf: Pergamon Press (1978) (12) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981)]**PEER REVIEWED**ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ethylene glycol mono-n-butyl ether, which has an experimental vapor pressure of 0.88 mm Hg at 25 deg C(2,SRC), will exist as a vapor in the ambient atmosphere. Vapor-phase ethylene glycol mono-n-butyl ether is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be about 20 hours(3,SRC). Particulate-phase ethylene glycol mono-n-butyl ether may be physically removed from the air by wet deposition(SRC).
[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Dow Chemical Company; The Glycol Ethers Handbook. The Dow Chemical Company, Midland, MI 97 pp (1990) (3) Atkinson R; Kinetics and Mechanisms of the Gas-Phase Reactions of the Hydroxyl Radical with Organic Compounds. Journal of Physical and Chemical Reference Data. Monograph No 1 (1989)]**PEER REVIEWED**Environmental Biodegradation:
A number of aerobic biological screening studies, which utilized settled waste water, sewage, or activated sludge for inocula, indicate that ethylene glycol mono-n-butyl ether should biodegrade rapidly in the environment(1-4). Five and ten-day Theoretical BOD values were 73% (with acclimation)(1) and 74%(2). The maximum Theoretical BOD reported was 88% for 20 days(2).
[(1) Bridie AL et al; Water Res 13: 627-30 (1979) (2) Price KS et al; J Water Pollut Contr Fed 46: 63-77 (1974) (3) Sasaki S; pp. 283-98 in Aquat Pollutants: Transform & Biolog Effects Hutzinger O et al ed Oxf: Pergamon Press (1978) (4) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981)]**PEER REVIEWED**A two-week biodegradation study using 30 mg/l sludge and an ethylene glycol mono-n-butyl ether concentration of 100 mg/l gave a theoretical BOD of 96%(1). The theoretical BODs for ethylene glycol mono-n-butyl ether after 5, 10, and 20 days have been determined to be 5, 57, and 72%(2). Biooxidation of ethylene glycol mono-n-butyl ether using a 20 day BOD test and a 28 day OECD test resulted in 88 and 75% degradation(3).
[(1) Chemicals Inspection and Testing Institute; Biodegradation and Bioaccumulation Data of Existing Chemicals Based on the CSCL Japan. Japan Chemical Industry Ecology - Toxicology and Information Center. ISBN 4-89074-101-1 (1992) (2) Dow Chemical Company; The Glycol Ethers Handbook. The Dow Chemical Company, Midland, MI 97 pp (1990) (3) Waggy GT et al; Environ Toxicol Chem 13: 1277-80 (1994)]**PEER REVIEWED**Environmental Abiotic Degradation:
The rate constant for the vapor-phase reaction of ethylene glycol mono-n-butyl ether with photochemically produced hydroxyl radicals has been experimentally determined to be 1.86x10-11 cu cm/molecule-sec at 25 deg C(1). This corresponds to an atmospheric half-life of about 20 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1,SRC). Alcohols and ethers are generally resistant to hydrolysis(2). They do not absorb UV light at environmentally significant wavelengths (>290 nm) and are commonly used as solvents for obtaining UV spectra(3). Therefore, ethylene glycol mono-n-butyl ether should not undergo hydrolysis or direct photolysis in the environment(SRC).
[(1) Atkinson R; Kinetics and Mechanisms of the Gas-Phase Reactions of the Hydroxyl Radical with Organic Compounds. Journal of Physical and Chemical Reference Data. Monograph No 1 (1989) (2) Silverstein RM, Bassler GC; Spectrometric Id Org Cmpd, J Wiley and Sons Inc p. 148-169 (1963) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington DC: Amer Chem Soc (1990)]**PEER REVIEWED**Environmental Bioconcentration:
An estimated BCF value of 2.5 was calculated for ethylene glycol mono-n-butyl ether(SRC), using an experimental log Kow of 0.83(1) and a recommended regression-derived equation(2). According to a recommended classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms is low(SRC).
[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Professional Reference Book. Heller SR (consult ed) Washington, DC: Amer Chem Soc pg 25 (1995) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington DC: Amer Chem Soc pp. 5-4, 5-10 (1990) (3) Franke C et al; Chemosphere 29: 1501-14 (1994)]**PEER REVIEWED**Soil Adsorption/Mobility:
The Koc of ethylene glycol mono-n-butyl ether is estimated as approximately 67(SRC), using an experimental log Kow of 0.83(1) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that ethylene glycol mono-n-butyl ether should have high mobility in soil(SRC).
[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Professional Reference Book. Heller SR (consult ed) Washington, DC: Amer Chem Soc pg 25 (1995) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington DC: Amer Chem Soc pp. 4-9 (1990) (3) Swann RL et al; Res Rev 85: 23 (1983)]**PEER REVIEWED**Volatilization from Water/Soil:
The Henry's Law constant for ethylene glycol mono-n-butyl ether is estimated as 2X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This value indicates that ethylene glycol mono-n-butyl ether will be essentially nonvolatile from water surfaces(2,SRC). Ethylene glycol mono-n-butyl ether's Henry's Law constant(1,SRC) indicate that volatilization from moist soil surfaces is not expected(SRC). The potential for volatilization of this compound from dry soil surfaces may exist(SRC) based on the measured vapor pressure of 0.88 mm Hg(3).
[(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) (3) Dow Chemical Company; The Glycol Ethers Handbook. The Dow Chemical Company, Midland, MI 97 pp (1990)]**PEER REVIEWED**Environmental Water Concentrations:
DRINKING WATER: Ethylene glycol mono-n-butyl ether was listed as a contaminant found in drinking water for a survey of US cities including Pomona, Escondido, Lake Tahoe and Orange Co, CA and Dallas, Washington, DC, Cincinnati, Philadelphia, Miami, New Orleans, Ottumwa, IA, and Seattle(1).
[(1) Lucas SV; GC/MS Anal of Org in Drinking Water Concentrates and Advanced Treatment Concentrates Vol 1 USEPA-600/1-84-020A (NTIS PB85-128239) p. 397 (1984)]**PEER REVIEWED**GROUNDWATER: Ethylene glycol mono-n-butyl ether was detected at a concn of 23 ug/l in 1 of 7 groundwater samples collected near "The Valley of Drums", KY(1). A ground water sample from an aquifer underlying a municipal landfill in Norman, OK contained ethylene glycol mono-n-butyl ether(2,3). Ethylene glycol mono-n-butyl ether was qualitatively identified in ground water in Milan, Italy near a paint factory where several underground tanks of solvents were located(4).
[(1) Stonebreaker RD, Smith AJ; pp 1-10 in Contr Haz Mater Spills, Proc Natl Conf Louisville KY (1980) (2) Dunlap WJ et al; Organic Pollutants Contributed to groundwater by a Landfill USEPA-600/9-76-004 p. 96-110 (1976) (3) Dunlap WJ et al; Identif Anal Org Pollut 1: 453-77 (1976) (4) Botta D et al; Comm Eur Comm Eur 8518 (Anal Org Micropollut water): 261-75 (1984)]**PEER REVIEWED**SURFACE WATER: In April 1980, ethylene glycol mono-n-butyl ether was detected in Hayashida River water (the Matsubara area in Tatsuno City, Hyogo Prefecture) at concn of 1310 and 5680 ppb(1). Ethylene glycol mono-n-butyl ether was identified in the Rhine River at Lobith at a concentration of 0.036 ug/l(2).
[(1) Yasuhara, A et al; Environ Sci Technol 15: 570-3 (1981) (2) Hendriks AJ et al; Wat Res 28: 581-98 (1994)]**PEER REVIEWED**Effluent Concentrations:
Ethylene glycol mono-n-butyl ether was identified in 1 and 4 neutral fractions of 33 industrial wastewater effluents at concn of <10 and <100 ug/l, respectively(4). Because ethylene glycol mono-n-butyl ether was detected in groundwater receiving municipal landfill leachate, it may be present in other landfill leachates(2,3). Ethylene glycol mono-n-butyl ether was listed as a volatile organic emission of silicone caulk(4). Ethylene glycol mono-n-butyl ether was detected in the emissions of waste incineration plants at 0.23 ug/cu m(5).
[(1) Dunlap WJ et al; Organic Pollutants Contributed to Groundwater by a Landfill USEPA-600/9-76-004 p. 96-110 (1976) (2) Dunlap WJ et al; Identif Anal Org Pollut 1: 453-77 (1976) (3) Tichenor BA, Mason MA; JAPCA 38: 264-8 (1988) (4) Perry DL et al; Iden of Org Compounds in Ind Effluent Discharges USEPA-600/4-79-016 (NTIS PB-294794) p. 230 (1979) (5) Jay K, Steiglitz L; Chemosphere 30: 1249-60 (1995)]**PEER REVIEWED**Atmospheric Concentrations:
INDOOR: According to the National Ambient Volatile Organic Compounds (VOCs) Database, the average daily indoor atmospheric concn of ethylene glycol mono-n-butyl ether is 0.214 ppbv for 14 samples(1). Ethylene glycol mono-n-butyl ether was detected at a concn of 8 ug/cu m in 1 of 6 samples of indoor air from 14 homes of northern Italy(2). Ethylene glycol mono-n-butyl ether was been identified in air from occupational buildings at concentrations of 1.8, 3.4, 3.9, 6.7, 8.5, 16, and 34 ug/cu m, in building exhaust at 6.0 and 13 ug/cu m, and in an elevator shaft at 19 ug/cu m(3).
[(1) Shah JJ, Singh HB; Environ Sci Technol 22: 1381-8 (1988) (2) DeBortoli M et al; Environ Int 12: 343-50 (1986) (3) Weschler CJ et al; Am Ind Hyg Assoc J 51: 261-68 (1990)]**PEER REVIEWED**Food Survey Values:
Ethylene glycol mono-n-butyl ether has been qualitatively identified in the volatile fraction of raw beef(1,2).
[(1) King MF et al; J Agric Food Chem 41: 1974-81 (1993) (2) Shahidi F et al; CRC Crit Rev Food Sci Nature 24: 141-243 (1986)]**PEER REVIEWED**Other Environmental Concentrations:
Ethylene glycol mono-n-butyl ether was contained in organic solvents with a frequency of occurrence of 0.4%(1). A paint stripping formulation was comprised of 35% ethylene glycol mono-n-butyl ether(2). Ethylene glycol mono-n-butyl ether was not detected in a machine cutting fluid prior to its use; however, the used fluid contained ethylene glycol mono-n-butyl ether at a concn of 0.060 ug/g(3).
[(1) Lehmann E et al; pp 31-41 in Safety and health aspects of organic solvents. Riihimaki V, Ulfvarson U eds Alan R Liss Inc. (1986) (2) Hahn WJ, Werschulz PO; Evaluation of alternatives to toxic organic paint strippers. NTIS PB86 219-177/AS USEPA 600/S2-86/063 (1986) (3) Yasuhara, A et al; Agric Bio Chem 50: 1765-70 (1986)]**PEER REVIEWED**Ethylene glycol mono-n-butyl ether was qualitatively detected in the headspace of liquid wax for marble, ceramic, linoleum, plastic, and varnished wood floors(1). Ethylene glycol mono-n-butyl ether was found in printer's inks used for serigraphy on paper and paper boards at concentrations of 0.1 and 0.4 wt%(2). Ethylene glycol mono-n-butyl ether has been identified as a major component of latex caulk(3). Ethylene glycol mono-n-butyl ether has been identified in a variety of household products including paints, primers and varnishes; all purpose cleaners; window and glass cleaners; engine degreasers; rug and upholstery cleaners; and metal cleaners and polishes(4).
[(1) Knoppel H, Schauenburg H; Environ Intl 15: 413-18 (1989) (2) Rastogi SC; Arch Environ Contam Toxicol 20: 543-47 (1991) (3) Tichenor BA; Environ Intl 15: 389-96 (1989) (4) USEPA; Compilation and Speciation of National Emissions Factors or Consumer/Commercial Solvent Use. Information Compiled to Support Urban Air Toxics Assessment Studies. Research Triangle Park,NC: USEPA Off Air Radiat, Off Air Qual Plan Stand, USEPA/450/2-89/008 NTIS PB89-207203 (1989)]**PEER REVIEWED**Environmental Standards & Regulations:
FIFRA Requirements:
Ethylene glycol monobutyl ether is exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only.
[40 CFR 180.1001(d) (7/1/94)]**PEER REVIEWED**TSCA Requirements:
Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Ethylene glycol mono-n-butyl ether is included on this list.
[40 CFR 716.120 (7/1/94)]**PEER REVIEWED**Atmospheric Standards:
This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Ethylene glycol monobutyl ether is produced, as an intermediate or final product, by process units covered under this subpart.
[40 CFR 60.489 (7/1/94)]**PEER REVIEWED**FDA Requirements:
Ethylene glycol monobutyl ether is an indirect food additive for use only as a component of adhesives.
[21 CFR 175.105 (4/1/93)]**PEER REVIEWED**Allowable Tolerances:
Ethylene glycol monobutyl ether is exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only.
[40 CFR 180.1001(d) (7/1/94)]**PEER REVIEWED**Chemical/Physical Properties:
Molecular Formula:
C6-H14-O2
**PEER REVIEWED**Molecular Weight:
118.20
**PEER REVIEWED**Color/Form:
...Colorless liquid.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 36]**QC REVIEWED**Odor:
... Mild, ether-like odor.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 36]**QC REVIEWED**Slight, rancid odor.
[Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994. 399]**PEER REVIEWED**Weak, pleasant odor.
[Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present.,p. VA24 496]**PEER REVIEWED**Boiling Point:
171-172 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 239]**PEER REVIEWED**Melting Point:
-70 deg C
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 71]**PEER REVIEWED**Critical Temperature & Pressure:
CRITICAL TEMP: 694 DEG F= 368 DEG C= 641 DEG K; CRITICAL PRESSURE: 470 PSIA= 32 ATM= 3.2 MEGANEWTONS/SQUARE M
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**Density/Specific Gravity:
SP GR: 0.9012 @ 20 DEG C/4 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 239]**PEER REVIEWED**Heat of Combustion:
-13,890 BTU/LB= -7720 CAL/G= -323X10+5 JOULES/KG
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**Heat of Vaporization:
157 BTU/LB= 87.1 CAL/G= 3.65X10+5 JOULES/KG
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**Octanol/Water Partition Coefficient:
log Kow= 0.83
[Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995. 25]**PEER REVIEWED**Solubilities:
SOL IN MOST ORG SOLVENTS, IN MINERAL OIL
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 239]**PEER REVIEWED**Mixes in all proportions with acetone, benzene, carbon tetrachloride, ethyl ether, n-heptane and water; miscible in all proportions with many ketones, ethers, alcohols, aromatic paraffin and halogenated hydrocarbons.
[Flick, E.W. (ed.). Industrial Solvents Handbook 4 th ed. Noyes Data Corporation., Park Ridge, NJ., 1991. 556]**PEER REVIEWED**water solubility = 1X10+6 mg/l
[Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985.]**QC REVIEWED**Spectral Properties:
SADTLER REF NUMBER: 2292 (IR, PRISM); 10979 (IR, GRATING)
[Weast, R.C. (ed.) Handbook of Chemistry and Physics. 69th ed. Boca Raton, FL: CRC Press Inc., 1988-1989.,p. C-273]**PEER REVIEWED**Index of refraction: 1.4198 @ 20 deg C/D
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 75th ed. Boca Raton, Fl: CRC Press Inc., 1994-1995.,p. 3-158]**PEER REVIEWED**Intense mass spectral peaks: 57 m/z (100%), 45 m/z (38%), 41 m/z (31%), 87 m/z (16%)
[Hites, R.A. Handbook of Mass Spectra of Environmental Contaminants. Boca Raton, FL: CRC Press Inc., 1985. 6]**PEER REVIEWED**IR: 1052 (Coblentz Society Spectral Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 624]**PEER REVIEWED**NMR: 4023 (Sadtler Research Laboratories Spectral Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 624]**PEER REVIEWED**Surface Tension:
Surface tension: 27.4 mN/m (=dyn/cm) @ 25 deg C.
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V21 389 (1983)]**PEER REVIEWED**Vapor Density:
4.1 (Air= 1)
[National Fire Protection Association. Fire Protection Guide on Hazardous Materials. 9th ed. Boston, MA: National Fire Protection Association, 1986.,p. 325M-51]**PEER REVIEWED**Vapor Pressure:
Vapor pressure = 0.88 mm Hg at 25 deg C
[Dow Chemical Company; The Glycol Ethers Handbook. The Dow Chemical Company, Midland, MI 97 pp (1990)]**PEER REVIEWED**Viscosity:
At 25 deg C= 2.83 centistokes
[Flick, E.W. (ed.). Industrial Solvents Handbook 4 th ed. Noyes Data Corporation., Park Ridge, NJ., 1991. 556]**PEER REVIEWED**Other Chemical/Physical Properties:
Acidity (as acetic acid), % by wt (max) 0.01.
[Flick, E.W. (ed.). Industrial Solvents Handbook 4 th ed. Noyes Data Corporation., Park Ridge, NJ., 1991. 556]**PEER REVIEWED**Blush resistance (@ 27 Deg C 96% rh; Coefficient of expension: 0.00092 cu cm
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V21 389 (1983)]**PEER REVIEWED**hydroxyl radical rate constant = 1.86X10-11 cu-cm/molc sec
[Atkinson R; Journal of Physical And Chemical Reference Data. Monograph No 1 (1989)]**QC REVIEWED**Chemical Safety & Handling:
DOT Emergency Guidelines:
Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**Fire or explosion: Combustible material: may burn but does not ignite readily. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**Public safety: CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number listed on the inside back cover. Isolate spill or leak area immediately for at least 25 to 50 meters (80 to 160 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing which is specifically recommended by the manufacturer. Structural firefighters' protective clothing is recommended for fire situations ONLY; it is not effective in spill situations.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**Evacuation: Spill: See the Table of Initial Isolation and Protective Action Distances for highlighted substances. For non-highlighted substances, increase, in the downwind direction, as necessary, the isolation distance shown under "PUBLIC SAFETY". Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**Fire: Small fires: Dry chemical, CO2 or water spray. Large fires: Water spray, fog or regular foam. Move containers from fire area if you can do it without risk. Dike fire control water for later disposal; do not scatter the material. Do not use straight streams. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from the ends of tanks. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**Spill or leak: Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Cover with plastic sheet to prevent spreading . Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**First aid: Move victim to fresh air. Call emergency medical care. Apply artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; induce artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved, and take precautions to protect themselves.
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**QC REVIEWED**Skin, Eye and Respiratory Irritations:
Irritation of eyes, nose and throat ...
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 155]**PEER REVIEWED**Fire Potential:
... Keep away from heat and open flame.
[Ash, M. and I. Ash. Encyclopedia of Industrial Chemical Additives. Vols 1, II, III. New York, NY: Chemical Publishing Co., Inc., 1984-1985.,p. V3 209]**PEER REVIEWED**NFPA Hazard Classification:
Health: 2. 2= Materials that, on intense or continued (but not chronic) exposure, could cause temporary incapacitation or possible residual injury, including those requiring the use of respiratory protective equipment that has an independent air supply. These materials are hazardous to health, but areas may be entered freely if personnel are provided with full-face mask self-contained breathing apparatus that provides complete eye protection.
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-51]**PEER REVIEWED**Flammability: 2. 2= Includes materials that must be moderately heated before ignition will occur and includes Class II and IIIA combustible liquids and and solids and semi-solids that readily give off ignitible vapors. Water spray may be used to extinguish fires in these materials because the materials can be cooled below their flash points.
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-51]**PEER REVIEWED**Reactivity: 0. 0= Includes materials that are normally stable, even under fire exposure conditions, and that do not react with water. Normal fire fighting procedures may be used.
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-51]**PEER REVIEWED**Flammable Limits:
Lower: 1.1% @ 93 deg C; Upper: 12.7% @ 135 deg C
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-51]**PEER REVIEWED**Flash Point:
143 DEG F (62 DEG C) (CLOSED CUP)
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-51]**PEER REVIEWED**Flash point = 69.4 deg C (open cup) and 60.0 deg C (closed cup)
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V11 944]**PEER REVIEWED**Autoignition Temperature:
238 deg C
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-51]**PEER REVIEWED**Fire Fighting Procedures:
CARBON DIOXIDE OR DRY CHEMICAL FOR SMALL FIRES; ALCOHOL-TYPE FOAM FOR LARGE FIRES.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped or safely confined. Use water in flooding quantities as fog. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use foam, dry chemical, or carbon dioxide. Keep run-off water out of sewers and water sources.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994. 473]**PEER REVIEWED**Hazardous Reactivities & Incompatibilities:
Incompatibilities: Strong oxidizers, strong caustics.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 155]**PEER REVIEWED**Strong oxidizers, strong caustics.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 36]**QC REVIEWED**Immediately Dangerous to Life or Health:
700 ppm
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 36]**QC REVIEWED**Protective Equipment & Clothing:
AIR PACK OR ORGANIC CANISTER RESPIRATOR, RUBBER GLOVES; GOGGLES; CLOTHING TO PREVENT BODY CONTACT WITH LIQ
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**Wear appropriate clothing to prevent repeated or prolonged skin contact. Wear eye protection to prevent any reasonable probability of eye contact. Employees should wash immediately when skin is wet or contaminated. Remove nonimpervious clothing immediately if wet or contaminated. Provide emergency showers.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 156]**PEER REVIEWED**Wear appropriate personal protective clothing to prevent skin contact.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Wear appropriate eye protection to prevent eye contact.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose could be considered adequate.]
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Recommendations for respirator selection. Max concn for use: 50 ppm. Respirator Class(es): Any chemical cartridge respirator with organic vapor cartridge(s). May require eye protection. Any supplied-air respirator. May require eye protection.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Recommendations for respirator selection. Max concn for use: 125 ppm. Respirator Class(es): Any supplied-air respirator operated in a continuous flow mode. May require eye protection. Any powered, air-purifying respirator with organic vapor cartridge(s). May require eye protection.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Recommendations for respirator selection. Max concn for use: 250 ppm. Respirator Class(es): Any chemical cartridge respirator with a full facepiece and organic vapor cartridge(s). Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister. Any powered, air-purifying respirator with a tight-fitting facepiece and organic vapor cartridge(s). May require eye protection. Any self-contained breathing apparatus with a full facepiece. Any supplied-air respirator with a full facepiece.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Recommendations for respirator selection. Max concn for use: 700 ppm. Respirator Class(es): Any supplied-air respirator that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Recommendations for respirator selection. Condition: Emergency or planned entry into unknown concn or IDLH conditions: Respirator Class(es): Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive pressure mode. Any supplied-air respirator that has a full facepiece and is operated in pressure-demand or other positive pressure mode in combination with an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive pressure mode.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Recommendations for respirator selection. Condition: Escape from suddenly occurring respiratory hazards: Respirator Class(es): Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister. Any appropriate escape-type, self-contained breathing apparatus.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Preventive Measures:
Contact lenses should not be worn when working with this chemical.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
**PEER REVIEWED**SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.
**PEER REVIEWED**The worker should immediately wash the skin when it becomes contaminated.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**Work clothing that becomes wet or significantly contaminated should be removed and replaced.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 37]**QC REVIEWED**If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue personnel hazard.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994. 473]**PEER REVIEWED**Personnel protection: Avoid breathing vapors. Keep upwind. ... Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994. 473]**PEER REVIEWED**Shipment Methods and Regulations:
No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
[49 CFR 171.2 (7/1/96)]**QC REVIEWED**The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.
[IMDG; International Maritime Dangerous Goods Code; International Maritime Organization p.6136 (1988)]**QC REVIEWED**Cleanup Methods:
1. VENTILATE AREA OF SPILL OR LEAK. 2. FOR SMALL QUANTITIES, ABSORB ON PAPER TOWELS. EVAPORATE IN SAFE PLACE (SUCH AS FUME HOOD). ALLOW SUFFICIENT TIME FOR EVAPORATING VAPORS TO COMPLETELY CLEAR HOOD DUCTWORK. BURN PAPER IN SUITABLE LOCATION AWAY FROM COMBUSTIBLE MATERIALS. 2. LARGE QUANTITIES CAN BE COLLECTED & ATOMIZED IN SUITABLE COMBUSTION CHAMBER. WASTE DISPOSAL: 1. BY ABSORBING IT IN VERMICULITE, DRY SAND, EARTH OR SIMILAR MATERIAL & DISPOSING IN SECURED SANITARY LANDFILL. 2. BY ATOMIZING IN SUITABLE COMBUSTION CHAMBER.
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981.]**PEER REVIEWED**IN SIMULATED WASTE GAS CONTAINING 1000 PPM ETHYLENE BUTYL MONOBUTYL ETHER WAS ABSORBED BY SPINDLE OIL 88 CONTAINING CALCIUM NAPHTHANATE, A NONIONIC SURFACTANT, AN ANTIOXIDANT & A STABILIZER.
[MURAMATSU S; JPN KOKAI TOKKYO PATENT NUMBER 80 18234 2/8/80 (NIHON JESCOAL INDUST CO, LTD)]**PEER REVIEWED**ACTIVATED SLUDGE DECOMPOSED ORGANIC SOLVENT CONTAINED IN ABSORBING LIQ OF WASTE GAS FROM PAINTING BOOTHS. ETHYLENE GLYCOL MONOBUTYL ETHER WAS DECOMPOSED BY ACCLIMATED SLUDGE.
[YASUDA M ET AL; KENKYU HOKOKU KANAGAWA-KEN KOGYO SHIKENSHO 48: 86 (1978)]**PEER REVIEWED**Disposal Methods:
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
**PEER REVIEWED**n-Butoxy ethanol should be atomized into an incinerator, and combustion may be improved by mixing with a more flammable solvent.
[United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland: United Nations Environmental Programme, Dec. 1985. 174]**PEER REVIEWED**The following wastewater treatment technologies have been investigated for Ethylene glycol monobutyl ether: Concentration process: Activated carbon.
[USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-152 (1982)]**PEER REVIEWED**Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit: Table Z-1 8-hr Time-Weighted Avg: 50 ppm (240 mg/cu m). Skin Designation.
[29 CFR 1910.1000 (7/1/98)]**QC REVIEWED**Vacated 1989 OSHA PEL TWA 25 ppm (120 mg/cu m), skin designation, is still enforced in some states.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 360]**QC REVIEWED**Threshold Limit Values:
8 hr Time Weighted Avg (TWA) 25 ppm, skin
[American Conference of Governmental Industrial Hygienists. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents Biological Exposure Indices for 1998. Cincinnati, OH: ACGIH, 1998. 21]**QC REVIEWED**Excursion Limit Recommendation: Excursions in worker exposure levels may exceed three times the TLV-TWA for no more than a total of 30 min during a work day and under no circumstances should they exceed five times the TLV-TWA, provided that the TLV-TWA is not exceeded.
[American Conference of Governmental Industrial Hygienists. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents Biological Exposure Indices for 1998. Cincinnati, OH: ACGIH, 1998. 6]**QC REVIEWED**Notice of Intended Change (first notice appeared in 1998 edition): The ACGIH has listed chemicals for which either a limit has been proposed for the first time, for which a change in the "Adopted" listing has been proposed, or for which retention on the Notice of Intended Changes has been proposed. The proposed limits should be considered trial limits that will remain in the listing for a period of at least one year. If, after one year no evidence comes to light that questions the appropriateness of the values herein, the values will be reconsidered for the "Adopted" list. Time Weighted Avg (TWA): 20 ppm.
[American Conference of Governmental Industrial Hygienists. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents Biological Exposure Indices for 1998. Cincinnati, OH: ACGIH, 1998. 73]**QC REVIEWED**NIOSH Recommendations:
NIOSH recommends reducing exposure to lowest feasible concn & preventing contact with the skin. /Glycol ether/
[NIOSH/CDC. NIOSH Recommendations for Occupational Safety and Health Standards 1988, Aug. 1988. (Suppl. to Morbidity and Mortality Wkly. Vol. 37 No. 5-7, Aug.26, 1988). Atlanta, GA: National Institute for Occupational Safety and Health, CDC, 1988. 16]**PEER REVIEWED**Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 5 ppm (24 mg/cu m). Skin.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 36]**QC REVIEWED**Immediately Dangerous to Life or Health:
700 ppm
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 36]**QC REVIEWED**Manufacturing/Use Information:
Major Uses:
IN HYDRAULIC FLUIDS
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 609]**PEER REVIEWED**The preferred coupling agent for many water-based coatings.
[CHEMICAL PRODUCTS SYNOPSIS: Glycol Ethers, 1983]**PEER REVIEWED**Used to make acetate esters as well as phthalate and stearate plasticizers.
[CHEMICAL PRODUCTS SYNOPSIS: Glycol Ethers, 1983]**PEER REVIEWED**A coupling agent to stabilize immiscible ingredients in metal cleaners, textile lubricants, cutting oils and liquid household products.
[CHEMICAL PRODUCTS SYNOPSIS: Glycol Ethers, 1983]**PEER REVIEWED**Solvent for nitrocellulose resins, spray lacquers, quick-drying lacquers varnishes, enamels, drycleaning cmpd, varnish removers, textile (preventing spotting in printing or dyeing), mutual solvent for "soluble" mineral oils to hold soap in solution and to improve the emulsifying properties.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 489]**PEER REVIEWED**Crude oil/water coupling solvent (oil-well work-overs); solvent (surface coatings, adhesives, organosol production).
[Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994. 399]**PEER REVIEWED**In vinyl and acrylic paints as well as lacquers and varnishes. Also in aqueous cleaners to solubilize organic surfactants.
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V4 696]**PEER REVIEWED**As a solvent in cosmetics.
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V7 585]**PEER REVIEWED**Manufacturers:
Dow Chemical USA, Hq, 2020 Dow Center, Midland, MI 48674, (517) 636-1000; Production site: Main St, Midland, MI 48667
[SRI. 1995 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1995 485]**PEER REVIEWED**Eastman Chemical Co, Hq, PO Box 511, Kingsport, TN 37662; Texas Eastman Division; Production site: Longview, TX 75607
[SRI. 1995 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1995 485]**PEER REVIEWED**Occidental Petroleum Corporation, Hq, 10889 Wilshire Blvd, Suite 1500, Los Angeles, CA 90024, (213) 879-1700; Petrochemicals, Occidental Tower, 5005 LBJ Freeway, PO Box 809050 (75380), Dallas, TX 75244 (214) 404-3800. Ethylene oxide and Derivatives Division; Production site: Bayport, TX 77000
[SRI. 1995 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1995 485]**PEER REVIEWED**Shell Chemical Co, Hq, One Shell Plaza, PO Box 2463, Houston, TX 77252-2463, (713) 241-6161; Production site: Geismar, LA 70734
[SRI. 1995 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1995 485]**PEER REVIEWED**Union Carbide Corporation, Hq, Old Ridgebury Road, Danbury, CT 06817, (203) 794-2000; Solvents and Intermediates; Production site: Seadrift, TX 77983
[SRI. 1995 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1995 485]**PEER REVIEWED**Methods of Manufacturing:
(1) BY REACTION OF ETHYLENE OXIDE WITH SUITABLE ALCOHOL, WITH VARIOUS CATALYSTS. (2) BY REACTING ETHYLENE CHLOROHYDRIN OR ETHYLENE GLYCOL WITH SODIUM HYDROXIDE & DIALKYL SULFIDE.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965. 609]**PEER REVIEWED**General Manufacturing Information:
OTHER EFFECTIVE FOG REDUCING MIXT TESTED INCL HEXADECANOL WITH OCTADECANOL & ETHYLENE MONOBUTYL ETHER.
[MCFADDEN TT ET AL; US ENVIRON PROT AGENCY, OFF RES DEV, (REP) EPA; ISS EPA-600/3-79-007, 51 PP (1979)]**PEER REVIEWED**Ethylene Glycol Monobutyl Ether is now /1983/ the largest volume glycol ether produced.
[CHEMICAL PRODUCTS SYNOPSIS: Glycol Ethers, 1983]**PEER REVIEWED**Formulations/Preparations:
GRADE: TECHNICAL
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 489]**PEER REVIEWED**Consumption Patterns:
41% AS SOLVENT FOR PROTECTIVE COATINGS; 18% AS SOLVENT FOR METAL CLEANERS AND LIQUID HOUSEHOLD CLEANERS; 9% FOR SYNTHESIS OF 2-BUTOXYETHYL ACETATE; 1% FOR SYNTHESIS OF DI(2-BUTOXYETHYL) PHTHALATE; 31% FOR OTHER SOLVENT USES (1972)
[SRI]**PEER REVIEWED**Intermediates, 20%; Coatings solvent, 65%; Miscellaneous solvents, 15% (1983)
[CHEMICAL PRODUCTS SYNOPSIS: Glycol Ethers, 1983]**PEER REVIEWED**U. S. Production:
(1972) 6.05X10+10 GRAMS
[SRI]**PEER REVIEWED**(1975) 5.93X10+10 GRAMS
[SRI]**PEER REVIEWED**(1984) 1.23X10+11 g
[USITC. SYN ORG CHEM-U.S. PROD/SALES 1984 p.257]**PEER REVIEWED**U. S. Imports:
(1972) NEGLIGIBLE
[SRI]**PEER REVIEWED**(1984) 4.02x10+7 g
[BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1984 p.1-361]**PEER REVIEWED**U. S. Exports:
(1972) 4.01X10+9 GRAMS
[SRI]**PEER REVIEWED**(1975) 5.45X10+9 GRAMS
[SRI]**PEER REVIEWED**(1984) 3.24X10+10 g
[BUREAU OF THE CENSUS. U.S. EXPORTS, SCHEDULE E, 1984 p.2-76]**PEER REVIEWED**Laboratory Methods:
Analytic Laboratory Methods:
NIOSH Method 1403. Analyte: Alcohols. Matrix: Air. Procedure: Gas chromatography, flame ionization detection. For 2-butoxyethanol, this method has an estimated detection limit of 0.01 to 0.02 mg/10 liters. The overall precision/RSD is 0.060 and the recovery is 92%. Applicability: This method may be used to determine two or more analytes simultaneously by varying GC conditions (eg, temperature). Interferences: High humidity reduces sampling capacity. Less volatile compounds may displace more volatile compounds on the charcoal.
[U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods. 4th ed.Methods A-Z & Supplements. Washington, DC: U.S. Government Printing Office, Aug 1994.,p. 1403-1]**PEER REVIEWED**DETERMINED IN WASTE WATER BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY.
[JUNGCLAUS ET AL; ANAL CHEM 48 (13): 1894 (1976)]**PEER REVIEWED**Gas chromatography is likely to be the analytical method for final analysis. Infrared absorption is sometimes used. /Glycol ethers/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3910]**PEER REVIEWED**Sampling Procedures:
In instances where materials are very soluble in water, samples of air can be taken effectively by scrubbing through water. /Glycol ethers/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 3910]**PEER REVIEWED**Special References:
Special Reports:
Jaraczewska W et al; Toxicology of butyl glycol; Med Pr 30 (5) 353 (1979). A review on the toxicity of butyl ethylene glycol, especially its CNS depressant effect & action inducing parenchymatous organ lesions.
USEPA; Health effects assessment for glycol ethers pp 90 (1984) EPA/540/1-86/052
Johanson G; Aspects of biological monitoring of exposure to glycol ethers; Toxicol Lett 43 (1-3): 5-21 (1988)
Miller RR; Metabolism and Disposition of Glycol Ethers; Drug Metab Rev 18 (1): 1-22 (1987).
Tyler TR, Acute and subchronic toxicity of ethylene glycol monobutyl ether, Environ Health Perspect, 185-91 (1984).
DHHS/NTP; NTP Technical Report on Toxicity Studies of Ethylene Glycol Ethers 2-Methoxyethanol, 2-Ethoxyethanol, 2-Butoxyethanol Administered in Drinking Water to F344/N Rats and B6C3F1 Mice. Toxicity Rpt Series No. 26 NIH Publication No. 93-3349 (1993)
Toxicology & Carcinogenesis Studies of 2-Butoxyethanol in F344/N Rats and B6C3F1 Mice p.6 Technical Report Series No. 484 (2000) NIH Publication No. 00-3974 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
Synonyms and Identifiers:
Synonyms:
A13-0993
**PEER REVIEWED**BUCS
**PEER REVIEWED**BUTOKSYETYLOWY ALKOHOL (POLISH)
**PEER REVIEWED**2-BUTOSSI-ETANOLO (ITALIAN)
**PEER REVIEWED**2-BUTOXY-AETHANOL (GERMAN)
**PEER REVIEWED**Butoxyethanol
**PEER REVIEWED**BETA-BUTOXYETHANOL
**PEER REVIEWED**N-BUTOXYETHANOL
**PEER REVIEWED**2-BUTOXYETHANOL
**PEER REVIEWED**2-BUTOXY-1-ETHANOL
**PEER REVIEWED**BUTYL CELLOSOLVE
**PEER REVIEWED**BUTYL CELLU-SOL
**PEER REVIEWED**Butylcelosolv (Czech)
**PEER REVIEWED**O-BUTYL ETHYLENE GLYCOL
**PEER REVIEWED**BUTYL GLYCOL
**PEER REVIEWED**BUTYLGLYCOL (FRENCH, GERMAN)
**PEER REVIEWED**BUTYL OXITOL
**PEER REVIEWED**Caswell No 121
**PEER REVIEWED**CHIMEC NR
**PEER REVIEWED**DOWANOL EB
**PEER REVIEWED**Ektasolve EB
**PEER REVIEWED**EPA Pesticide Chemical Code 011501
**PEER REVIEWED**Eter monobutilico del etilenglicol (Spanish)
**PEER REVIEWED**ETHANOL, 2-BUTOXY-
**PEER REVIEWED**Ether monobutylique de L'ethyleneglycol (French)
**PEER REVIEWED**ETHYLENE GLYCOL BUTYL ETHER
**PEER REVIEWED**ETHYLENE GLYCOL N-BUTYL ETHER
**PEER REVIEWED**Ethylene glycol monobutyl ether
**PEER REVIEWED**GAFCOL EB
**PEER REVIEWED**GLYCOL BUTYL ETHER
**PEER REVIEWED**GLYCOL MONOBUTYL ETHER
**PEER REVIEWED**MONOBUTYL ETHER OF ETHYLENE GLYCOL
**PEER REVIEWED**Monobutyl ethylene glycol ether
**PEER REVIEWED**MONOBUTYL GLYCOL ETHER
**PEER REVIEWED**3-Oxa-1-heptanol
**PEER REVIEWED**POLY-SOLV EB
**PEER REVIEWED**
