NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
Prepared by Tim Borges, Ph.D., Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.
Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM.
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under contract No. DE-AC05-84OR21400.
This report is an update of the Toxicity Summary for cis- and trans-1,2-Dichloroethylene (CAS Registry Nos. 156-59-2 and 156-60-5, respectively). The original summary for this chemical was submitted in December 1991. The update was performed by incorporating any new human health toxicity data published since the original submittal of the report. Pertinent pharmacokinetic, toxicologic, carcinogenic, and epidemiologic data were obtained through on-line searches of the TOXLINE database from 1991 through 1994. In addition, any changes to EPA-approved toxicity values (reference doses, reference concentrations, or cancer slope factors) from the Integrated Risk Information System (IRIS) (current as of December 1994) and/or the Health Effects Assessment Summary Tables, Annual FY-94 and July Supplement No. 1, for this chemical were incorporated in this update.
1,2-Dichloroethene exists in two isomeric forms, cis-1,2-dichloroethene and trans-1,2-dichloroethene, that are colorless, volatile liquids with a slightly acrid odor. Although not used extensively in industry, 1,2-dichloroethene is used in the production of other chlorinated solvents and as a solvent for dyes, perfumes, and lacquers (Sax and Lewis 1989, Budavari et al. 1989). Humans are exposed to 1,2-dichloroethene primarily by inhalation, but exposure can also occur by oral and dermal routes.
Limited information exists on the absorption, distribution, and excretion of 1,2-dichloroethene in either humans or animals. In vitro studies have shown that the mixed function oxidases will metabolize 1,2-dichloroethene; the final metabolic products are dependent on the initial isomer of 1,2-dichloroethene (Costa and Ivanetich 1984, Henschler 1977, Liebman and Ortiz 1977).
Information on the toxicity of 1,2-dichloroethene in humans and animals is limited. Workers exposed to 1,2-dichloroethene have been reported to suffer from drowsiness, dizziness, nausea, fatigue, and eye irritation (ATSDR 1990). Acute and subchronic oral and inhalation animal studies of trans-1,2-dichloroethene and acute inhalation animal studies of cis-1,2-dichloroethene suggest that the liver is the primary target organ. The toxicity is expressed in increased activities of liver associated enzymes, fatty degeneration, and necrosis (McCauley et al. n.d., Barnes et al. 1985, Freundt et al. 1977). Secondary target organs include the central nervous system and lung.
Based on an unpublished study describing decreased hemoglobin and hematocrits in rats treated by gavage for 90 days, EPA (1994a,b) assigned a subchronic and chronic oral reference dose (RfD) for cis-1,2-dichloroethene of 1.00E-01 mg/kg/day and 1.00E-02 mg/kg/day, respectively. The RfDs were derived from a no-observed-adverse-effect-level/lowest-observed-adverse-effect-level (NOAEL/LOAEL) of 32 mg/kg/day. An inhalation reference concentration (RfC) for cis-1,2-dichloroethene has not been derived.
Subchronic and chronic RfDs of 2.00E-01 mg/kg/day and 2.00E-02 mg/kg/day, respectively, for trans-1,2-dichloroethene have been calculated (EPA 1994a, b). The RfDs were derived from a LOAEL of 175 mg/kg/day that was based on increased serum alkaline phosphatase activity in mice that received trans-1,2-dichloroethene in their drinking water (EPA 1994a,b). An RfC for trans-1,2-dichloroethene has not been derived.
No information was available concerning the chronic, developmental, or reproductive toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene. No cancer bioassays or epidemiological studies were available to assess the carcinogenicity of 1,2-dichloroethene. EPA (1994b) has placed both cis-1,2-dichloro-ethene and trans-1,2-dichloroethene in weight-of-evidence group D, not classifiable as to human carcinogenicity, based on the lack of human or animal carcinogenicity data and on essentially negative mutagenicity data. Oral and inhalation slope factors have not been calculated for these isomers.
1,2-Dichloroethene (CAS No. 540-59-0) is also known by the synonyms 1,2-dichloroethylene, acetylene dichloride, and dioform. The compound has two isomeric forms, cis-1,2-dichloroethene (CAS No. 156-59-2) and trans-1,2-dichloroethene (CAS No. 156-60-5). Both are colorless, volatile liquids with ethereal and slightly acrid odors and have molecular weights of 96.94 (Sax and Lewis 1989, Budavari et al. 1989). 1,2-Dichloroethene is slightly soluble in water (cis-1,2-dichloroethene - 3.5 g/L; trans-1,2-dichloroethene - 6.3 g/L), but is very soluble in alcohol, ether, acetone and most other organic solvents (Budavari et al. 1989, Weast 1988). cis-1,2-Dichloroethene has a vapor pressure of 200 mm Hg at 25C, a melting point of -81.47C, a boiling point of 60.2C, and a flash point of 4C. The vapor pressure, melting point, boiling point, and flash point of trans-1,2-dichloroethene are 320 mm Hg, -49.44C, 47.7C, and 2C, respectively
1,2-Dichloroethene is prepared commercially by either the direct chlorination of acetylene or by the reduction of 1,1,2,2-tetrachloroethane with fractional distillation used to separate the two isomers (Stevens 1979). 1,2-Dichloroethene can also be formed as a by-product during the manufacture of other chlorinated compounds. Commercial use is not extensive, but trans-1,2-dichloroethene and mixtures of cis- and trans-1,2-dichloroethene have been used as intermediates in the production of other chlorinated solvents and compounds, as well as low temperature extraction solvents for dyes, perfumes, and lacquers. Both cis- and trans-1,2-dichloroethene are moderately flammable and react with alkalies to form chloracetylene gas, which spontaneously ignites in air. Additionally, cis- and trans-1,2-dichloroethene react violently with potassium hydroxide, sodium, and sodium hydroxide and form shock-sensitive explosives when combined with dinitrogen tetraoxide (Sax and Lewis 1989). 1,2-Dichloroethene emits chlorine gas when heated to decomposition.
Because of its volatility, the primary route of 1,2-dichloroethene exposure to humans is by inhalation. Exposure to 1,2-dichloroethene may occur as a result of releases from production and use facilities, contaminated waste disposal sites and wastewaters, and burning of polyvinyl and vinyl copolymers (ATSDR 1990). 1,2-Dichloroethene contaminates groundwater supplies by leaching from waste disposal sites. Therefore, human oral, dermal, and inhalation exposure can occur from drinking, using, and breathing vapors from 1,2-dichloroethene contaminated supplies and delivery systems.
Sato and Nakajima (1987) reported that the blood/air partition coefficients at 37C for cis-1,2-dichloroethene and trans-1,2-dichloroethene were 9.2 and 5.8, respectively, but tissue/blood partition coefficients have not been reported. In addition, Filser and Bolt (1979) have reported that during inhalation exposure, cis-1,2-dichloroethene and trans-1,2-dichloroethene reach whole-body equilibrium within 1.5-2 hours. EPA (1980) has estimated that the absorption of 1,2-dichloroethene following oral exposure is virtually complete and is approximately 35-50% following inhalation exposure. Other information on the absorption of 1,2-dichloroethene was not available, but studies that describe histological changes to the heart and liver following treatment with trans-1,2-dichloroethene (Freundt et al., 1977) provide indirect evidence of absorption.
Information on the distribution of cis-1,2-dichloroethene or trans-1,2-dichloroethene following absorption was not available. However, studies that describe histological changes to the heart and liver following trans-1,2-dichloroethene treatment provides indirect evidence that distribution occurs to these organs (Freundt et al. 1977).
The metabolism of 1,2-dichloroethene is mediated by the mixed function oxidase system. In vitro studies have established that chlorinated epoxides of 1,2-dichloroethene, formed through a Type 1 interaction with cytochrome P-450, are the initial products of metabolism (Costa and Ivanetich 1982). The epoxides are transformed to dichloroacetaldehyde either by spontaneous rearrangement or through the action of epoxide hydrolase (Costa and Ivanetich 1984, Henschler 1977, Liebman and Ortiz 1977). Secondary metabolism of the aldehyde produced from cis-1,2-dichloroethene by mitochondrial and cytosolic aldehyde and alcohol dehydrogenases yields primarily dichloroethanol with minor concentrations of dichloroacetate. In contrast, metabolism of the aldehyde produced from trans-1,2-dichloroethene yields primarily dichloroacetate with only minor amounts of dichloroethanol (Costa and Ivanetich 1984).
Information on the excretion of cis-1,2-dichloroethene and trans-1,2-dichloroethene was not available.
Information on the acute oral toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene in humans was not available.
Studies on the acute oral toxicity of cis-1,2-dichloroethene to animals are not available. Freundt et al. (1977) reported that the LD50 of trans-1,2-dichloroethene in Wistar rats treated by gavage was 1 mL/kg (1263 mg/kg). Additional details of the study were not provided. Hayes et al. (1987) reported that the LD50 of trans-1,2-dichloroethene in Sprague-Dawley rats was 7902 mg/kg in males and 9939 mg/kg in females. The severity of ataxia and depression of the central nervous system and respiratory system were dose related.
Barnes et al. (1985) reported that the LD50 of CD-1 mice treated with trans-1,2-dichloroethene by gavage was 2122 mg/kg for males and 2391 mg/kg for females. Dose-related signs of clinical toxicity, ataxia, suppressed righting reflex, and respiratory depression were observed. Barnes et al. (1985) also reported the results of a 14-day study in which male CD-1 mice were treated daily by gavage with 0, 21 or 210 mg/kg/day trans-1,2-dichloroethene. No significant differences relative to control mice were observed with respect to weight gain or body, brain, liver, spleen, lung, thymus, kidney, or testes weight. A significant 12% decrease in plasma fibrinogen and a 7% decrease in plasma prothrombin time were reported for mice treated with 210 mg/kg/day 1,2-dichloroethene. The hemoglobin, hematocrit, white blood cell count, blood urea nitrogen, lactic acid dehydrogenase activity, and serum glutamic pyruvate transaminase (SGPT) activity were not affected by treatment (Barnes et al. 1985). In a concurrent study, Shopp et al. (1985) reported that trans-1,2-dichloroethene did not affect the humoral immune status of male and female CD-1 mice.
Kallman et al. (1983) reported that the LD50 of mice exposed for 7 days to a mixture of both isomers of 1,2-dichloroethene was 1000 mg/kg.
Information on the subchronic oral toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene in humans was not available.
EPA (1990b, McCauley et al. n.d.) reported in an unpublished study that a dose of 32 mg/kg/day of cis-1,2-dichloroethene by gavage for 90 days decreased the hemoglobin and hematocrit of rats. Additional information on this study was not available.
Hayes et al. (1987) reported the results of a study using male and female Sprague-Dawley rats that received doses of 500, 1500, or 3000 mg/kg trans-1,2-dichloroethene in their drinking water for 90 days. The authors reported that other than a dose-dependent decrease in the absolute and relative kidney weight of female rats treated with 1500 and 3000 mg/kg (equivalent to 1257 and 2809 mg/kg/day, respectively), signs of toxicity were not observed in clinical chemistry, hematology or urinalysis parameters, body or organ weights, or organ histopathology. No trans-1,2-dichloroethene-related deaths of rats were reported.
Barnes et al. (1985) conducted a study in which groups of 140 male and 140 female CD-1 mice received 0.1, 1.0, or 2.0 mg/mL trans-1,2-dichloroethene in their drinking water for 90 days. These doses were equivalent to 16.8, 175, or 387 mg/kg/day for male mice and 22.6, 224, or 452 mg/kg/day for female mice. The results of trans-1,2-dichloroethene treatment were compared with groups of 240 male and 240 female CD-1 control mice. No dose-related treatment effects, either between or within sexes of mice, were reported. However, a significant increase in the absolute and relative liver weight of male mice treated with 175 mg/kg/day and a significant decrease in the absolute and relative lung and thymus weights of female mice treated with 452 mg/kg/day trans-1,2-dichloroethene were observed. Male mice treated with 16.8 and 175 mg/kg/day trans-1,2-dichloroethene had a significant decrease in plasma prothrombin time, and male mice treated with 175 or 387 mg/kg/day had a significant increase in serum glucose and alkaline phosphatase (AP) activity. Male mice treated with 387 mg/kg/day trans-1,2-dichloroethene had decreased hepatic glutathione levels. Female mice treated with 224 mg/kg/day trans-1,2-dichloroethene had a significant increase in the total white blood cell count, and female mice treated with 224 or 452 mg/kg/day had a significant decrease in serum calcium and the activities of SGPT and serum glutamic oxaloacetate transaminase.
The hepatic activity of aniline hydroxylase was decreased in all three female mouse treatment groups and in male mice treated with 175 mg/kg/day trans-1,2-dichloroethene. Male mice treated with 175 mg/kg/day and female mice treated with 224 mg/kg/day had decreased activity of hepatic aminopyrine N-demethylase. No treatment-related effects to the activities of total cytochrome P-450 or cytochrome b5 in male or female mice were found.
Studies that assessed the humoral immune status of CD-1 male and female mice, conducted in conjunction with the Barnes et al. (1985) 90-day drinking water study, were reported by Shopp et al. (1985). Four days after the start of treatment with 16.8, 175 or 387 mg/kg/day trans-1,2-dichloroethene, the number of antibody forming cells per spleen of male mice challenged with concanavalin A was significantly (p<0.05) decreased relative to the dose. By day 5 of treatment, only male mice treated with 387 mg/kg/day trans-1,2-dichloroethene had decreased antibody forming cells. The number of antibody forming cells was not affected by trans-1,2-dichloroethene treatment in female mice, and the hemagglutination titers to sheep red blood cells were not affected in either sex. However, female mice treated with 452 mg/kg/day trans-1,2-dichloroethene had an enhanced spleen lymphocyte response to lipopolysaccharide stimulation. In addition, spleen lymphocyte responsiveness in the absence of lipopolysaccharide was decreased in female mice treated with 224 and 452 mg/kg/day trans-1,2-dichloroethene.
Information on the chronic oral toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene in humans or animals was not available.
Information on the developmental and reproductive toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene in humans or animals was not available.
Specific information on the acute inhalation toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene to humans was not available; however, it has been reported that humans exposed to high concentrations of 1,2-dichloroethene develop clinical symptoms of nausea, drowsiness, dizziness, fatigue, and eye irritation (ATSDR 1990).
Freundt et al. (1977) reported that groups of six adult female Wistar rats exposed to trans-1,2-dichloroethene at concentrations of 200, 1000, or 3000 ppm for 8 hours or to 200 ppm 5 days/week for 1 or 2 weeks developed fat accumulation in the hepatocytes and Kupffer cells of the liver and capillary hyperemia of the lung. Rats exposed to 1000 ppm trans-1,2-dichloroethene for 8 hours had significantly decreased (p<0.05) serum concentrations of albumin and urea nitrogen and decreased alkaline phosphatase activity. (These results are of questionable biological significance because none were outside the established normal range for the species.) In addition, rats exposed to 3000 ppm trans-1,2-dichloroethene developed fibrous swelling and hyperemia of the cardiac muscle.
Freundt and Macholz (1978) reported the results of studies in which adult female SPF Wistar rats were exposed for 8 hours to concentrations of 0, 200, 600, 1000, or 3000 ppm cis-1,2-dichloroethene and trans-1,2-dichloroethene. Although the inhalation treatment of rats with either isomer of 1,2-dichloroethene produced a significant (p<0.05) and dose-dependent increase in the hexobarbital sleeping time and zoxazolamine paralysis time, the effects produced by cis-1,2-dichloroethene were greater than those of trans-1,2-dichloroethene. In addition, both isomers of 1,2-dichloroethene produced a significant (p<0.05) and dose-dependent reversible inhibition in the formation of free aminoantipyrene. Freundt and Macholz (1978) also reported that the addition of 1000 ppm trans-1,2-dichloroethene to rat microsomes competitively inhibited the N-demethylation of aminopyrine and the O-demethylation of p-nitroanisole.
Information on the subchronic inhalation toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene in humans was not available.
Information on the subchronic inhalation toxicity of cis-1,2-dichloroethene to animals was not available. Freundt et al. (1977) exposed two groups of six adult female Wistar rats to trans-1,2-dichloroethene for 8 or 16 weeks and compared the results to concurrent control rats. The rats were exposed to atmospheric concentrations of 200 ppm 8 hours/day, 5 days/week. At the end of each exposure period, the liver, lungs, kidneys, spleen, brain, quadriceps muscle, and sciatic nerve were removed and examined microscopically. Following 8 or 16 weeks of 1,2-dichloroethene exposure, fatty degeneration of the hepatocytes and Kupffer cells of 3/6 treated rats, as well as capillary hyperemia of the lung in 6/6 rats were observed.
Information on the chronic inhalation toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene in humans or animals was not available.
Information on the developmental and reproductive toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene in humans or animals following inhalation exposure was not available.
Reference concentrations for cis-1,2-dichloroethene and trans-1,2-dichloroethene have not been derived.
Information on the toxicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene from routes of exposure other than oral or inhalation was not available.
The McCauley et al. (n.d.) study describes decreased hemoglobin and hematocrits in rats following treatment with cis-1,2-dichloroethene. However, the assessment of cis-1,2-dichloroethene target organ toxicity is precluded because the study is unpublished.
Liver: Treatment of CD-1 mice with trans-1,2-dichloroethene by gavage or in the drinking water decreased the plasma fibrinogen and prothrombin time. Male mice treated for 90 days with 175 or 387 mg/kg/day trans-1,2-dichloroethene had increased serum AP activities, and male mice treated with 387 mg/kg/day had decreased hepatic glutathione levels.
Central Nervous System: Treatment of male and female CD-1 mice decreased the righting reflex of mice and produced ataxia and respiratory depression.
1,2-Dichloroethene - Isomeric Mixture
Central Nervous System: Humans acutely exposed to high concentrations of 1,2-dichloroethene have been reported to develop nausea, dizziness, fatigue, and drowsiness.
Liver: Exposure of rats to 1000 ppm cis-1,2-dichloroethene produced a dose-dependent increase in the hexobarbital sleeping time and zoxazolamine paralysis time.
Liver: trans-1,2-dichloroethene has been reported to decrease serum albumin, increase the hexobarbital sleeping time and zoxazolamine paralysis time, inhibit the N-demethylation of aminopyrine and the O-demethylation of p-nitroanisole, and produce fatty degeneration of hepatocytes of rats.
1,2-Dichloroethene - Isomeric mixture
Eyes: Humans acutely exposed to high concentrations of 1,2-dichloroethene have been reported to develop eye irritation.
Because of the lack of available information, secondary target organs cannot be described.
Information on the carcinogenicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene following oral exposure in humans or animals was not available.
Information on the carcinogenicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene following inhalation exposure in humans or animals was not available.
Information on the carcinogenicity of cis-1,2-dichloroethene or trans-1,2-dichloroethene from other routes of exposure in humans or animals was not available.
Classification--D; not classifiable as to human carcinogenicity (EPA 1994b).
Basis--No data in humans or animals and essentially negative results in mutagenicity assays.
Classification--D; not classifiable as to human carcinogenicity (EPA 1994b).
Basis--No data in humans or animals and essentially negative results in utagenicity assays.
Oral slope factors have not been calculated for cis-1,2-dichloroethene or for trans-1,2-dichloroethene.
Inhalation slope factors have not been calculated for cis-1,2-dichloroethene or for trans-1,2-dichloroethene.
ATSDR (Agency for Toxic Substances and Disease Registry). 1990. Draft Toxicological Profile for 1,2-dichloroethene. Prepared by Clement Assoc., Inc. under contract 205-88-0608. U.S. Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA, p. 1-101.
Barnes, D.W., V.M. Sanders, K.L. White, G.M. Shopp and A.E. Munson. 1985. Toxicology of trans-1,2-dichloroethylene in the mouse. Drug and Chem. Toxicol. 8(5): 373-392.
Budavari, S., M.J. O'Neil, A. Smith and P.E. Heckelman. 1989. In: The Merck Index, 11th ed., Merck & Co., Inc., Rahway, NJ, p. 15.
Costa, A.K. and K.M. Ivanetich. 1982. The 1,2-dichloroethylenes: Their metabolism by hepatic cytochrome P-450 in vitro. Biochem. Pharmacol. 31: 2083-2092.
Costa, A.K. and K.M. Ivanetich. 1984. Chlorinated ethylenes: Their metabolism and effect on DNA repair in rat hepatocytes. Carcinogenesis 5: 1629-1636.
Filser, J.G. and H.M. Bolt. 1979. Pharmacokinetics of halogenated ethylenes in rats. Arch. Toxicol. 42: 123-136. (Cited in ATSDR, 1990.)
Freundt, K.J. and J. Macholz. 1978. Inhibition of mixed function oxidases in rat liver by trans- and cis-1,2-dichloroethene. Toxicology 10: 131-139.
Freundt, K.J., G.P. Liebaldt and E. Lieberwirth. 1977. Toxicity studies on trans-1,2-dichloroethene. Toxicology 7: 141-153.
Hayes, J.R., L.W. Condie, J.L. Egle and J.F. Borzelleca. 1987. The acute and subchronic toxicity in rats of trans-1,2-dichloroethene in drinking water. J. Am. Coll. Toxicol. 6(4): 471-478.
Henschler, D. 1977. Metabolism and mutagenicity of halogenated olefins -- A comparison of structure and activity. Environ. Health Perspec. 21: 61-64.
Kallman, M.J., M.R. Lynch and M.R. Landauer. 1983. Taste aversions to several halogenated hydrocarbons. Neurobehav. Toxicol. Teratol. 5: 23-27. (Cited in ATSDR, 1990.)
Liebman, K.C. and E. Ortiz. 1977. Metabolism of halogenated ethylenes. Environ. Health Perspec. 21: 91-97.
McCauley, P.T., M. Robinson, L.W. Condie and M. Parvell. n.d. The effects of subacute and subchronic oral exposure to cis-1,2-dichloroethylene in rats. Health Effects Research Laboratory, EPA, Cincinnati, OH.
Sato, A. and T. Nakajima. 1987. Pharmacokinetics of organic solvent vapors in relation to their toxicity. Scand. J. Work Environ. Health 13: 81-93.
Sax, N.I. and R.J. Lewis. 1989. In: Properties of Industrial Materials, 7th ed., Volume III, Van Nostrand Reinhold Co., New York, NY, p. 1152.
Shopp, G.M., V.M. Sanders, K.L. White and A.E. Munson. 1985. Humoral and cell-mediated immune status of mice exposed to trans-1,2-dichloroethylene. Drug Food Chem. Toxicol. 8(5): 393-407.
Stevens, V.L. 1979. 1,2-Dichloroethylene. In: Kirk-Othmer encyclopedia of Chemical Technology, 3rd ed., Vol. 5. M. Grayson and D. Eckroth, eds., John Wiley and Sons, New York, NY, pp. 742-745.
U.S. Environmental Protection Agency (EPA). 1980. Ambient Water Quality Criteria for Dichloroethylenes. Environmental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-041. NTIS PB 81-117525.
U.S. Environmental Protection Agency (EPA). 1994a. Health Effects Assessment Summary Tables (HEAST), Annual FY-94. Prepared by the Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC.
U.S. Environmental Protection Agency (EPA). 1994b. Integrated Risk Information System (IRIS). Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH.
Weast, R.C., Ed. 1988. In: CRC (Chemical Rubber Company) Handbook for Chemistry and Physics, 69th ed. M.J. Astle and W.H. Beyer, Assoc. Ed., CRC Press, Inc., Boca Raton, FL. p. C-56. Retrieve Toxicity Profiles Condensed Version
Last Updated 10/31/97