ATTACHMENTS TARGETED RISK ASSESSMENT FORMER HULETT LAGOON

CAMDENTON, MISSOURI TOXICOLOGICAL PROFILES

1,2-Dichloroethene (DCE)

1,2-DCE is a colorless, flammable liquid with a sharp, harsh odor. There are two forms of 1,2-DCE: cis-1,2-DCE and trans-1,2-DCE. Both forms can be present as a mixture. Neither of these isomers has developed wide industrial usage due to their flammability. Overall, trans-1,2-DCE is more widely used than cis-1,2-DCE and the 1,2-DCE mixture. 1,2-DCE is used either as a low-temperature extraction solvent or as a direct solvent in materials such as dyes, perfume oils, waxes, resins, and thermoplastics. It is also used as a captive intermediate in the production of other chlorinated solvents. 1,2-DCE can be biodegradation products of PCE and TCE. The toxicity of 1,2-DCE has been reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR) (ATSDR, 1994), U.S. Environmental Protection Agency (USEPA) (USEPA, 1987), and Massachusetts Department of Environmental Protection (MDEP) (MDEP, 1992).

1,2-DCE is absorbed by all routes of exposure with rapid distribution to high lipid tissues. Its metabolic products are chloroethylene epoxides and dichloroacetaldehyde or chloroacetic acids.

At high concentrations, like other chlorinated ethylenes, 1 ,2-DCE possesses anesthetic properties. It was once used as a general inhalation anesthetic in humans, and the trans-isomer appears to be about twice as potent as the cis-isomer in depressing the central nervous system. The most significant and sensitive effects of 1,2-DCE are on the liver and the blood system. At high-exposure levels, clinical symptoms reported were nausea, drowsiness, fatigue, intracranial pressure, and ocular irritation. There are no reports of long-term human exposure to 1 ,2-DCE.

Animal toxicological data on 1,2-DCE are limited because the compound is not widely used in the industry. Pathological lesions of the heart, liver, and lungs have been reported in rats exposed to trans-1,2-DCE in air. Ataxia Uerky movement) and respiration depression occur in the terminal stages prior to death in animals. The relevance of these conditions to public health is not known because they have not been reported in humans.

The majority of genotoxicity tests on both isomers of 1,2-DCE have been negative. There are no carcinogenicity studies on 1,2-DCE found in the literature. The USEPA has determined cis-1,2-DCE to be a class D chemical (not classifiable as to human carcinogenicity) (USEPA, 2004) .

Trichloroethene (TCE)

TCE is a clear, colorless, and widely used solvent, especially for metal degreasing, which consumes about 90 percent of TCE produced annually in the United States. TCE is also used for dry cleaning, as a low-temperature heat exchange fluid, as a fumigant, as a diluent in paints and adhesives, in aerospace operations, and in textile processing.

( Previously, TCE was used as an extractant in food processing. These uses were discontinued in 1975 due to evidence of possible carcinogenic activity. Its earlier use in anesthetics was also discontinued. TCE has been reviewed by ATSDR (1991 ), USEPA (1980, 1983, 1984, and 1987), and MDEP (1992) .

TCE is rapidly and extensively absorbed after inhalation and ingestion, and to some extent through intact skin . TCE tends to collect in 'adipose tissue. The compound is extensively metabolized in humans to trichloroethanol, trichloroethanol glucuronide, and trichloroacetic acid, at least some of which are responsible for much of TCE's toxicity. Although the liver is the primary site of TCE metabolism, there is evidence for extrahepatic metabolism in the lungs and kidneys. TCE metabolites are excreted primarily in the urine. TCE interacts with a number of other chemicals, including ethanol, generally increasing the severity of effects of both compounds.

Acute inhalation exposures to TCE cause central nervous system depression and some irritation. The effects seen in humans range from mild eye and throat irritation, nausea, vertigo, headache, and drowsiness to loss of consciousness and death. TCE was once used as a surgical anesthetic, but this practice was abandoned because of side effects, in particular cardiac sensitization , upon the effects of the body's own control mechanisms. Death due to cardiac, liver, kidney, or pancreatic failure has also been observed in humans acutely exposed to TCE via inhalation or ingestion.

Long-term chronic exposures to TCE in occupational settings have been associated with dizziness, fatigue, headache, short-term memory loss, and blurred vision . Anorexia, nausea, vomiting, and ,fat intolerance have also been observed. No information is available on the effects of chronic TCE ingestion by humans. In animals chronically exposed to TCE via the oral route, central nervous system toxicity, liver and kidney lesions, immunological effects, as well as peripheral neuritis, were observed. Environmental exposure to TCE in air, water, or soil is not expected to pose significant risk to the human respiratory, cardiovascular, or hepatic system (ATSDR 1991 ).

There is limited evidence that would link TCE exposure to developmental and reproductive effects in humans. Results of occupational and epidemiological studies have been complicated because of the fact that people under study were also exposed to other solvents other than TCE. Animal studies using both inhalation and oral routes did not reveal teratogenic effects on the developing fetus. Mice and rats given TCE in the diet or by gavage had very few adverse effects on fertility other than changes in the weight of the testes. One oral mouse study reported abnormal sperm morphology following exposure to very high levels of TCE, but this study did not test for fertility, or reproductive outcome; therefore, the biological significance of these observed effects in animals is unknown.

The data regarding genotoxicity of TCE in humans, in vivo animals, and in vitro studies are inconclusive. TCE was found to be carcinogenic in some animal tests, but no human data are currently available. One problem associated with some of the animal studies is the use of TCE containing small amounts of preservative epoxide stabilizers, which themselves may be carcinogens.

Currently, the USEPA is reviewing the weight-of-evidence classification for TCE. In 1988, the USEPA Science Advisory Board offered an opinion that the weight-of-evidence for TCE be on C-82 continuum (Possible Human

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Carcinogen-Probable Human Carcinogen) . In 1989, the USEPA withdrew the IRIS carcinogenicity file for TCE and has not adopted a current position on the weight-of-evidence classification .

REFERENCES

Agency for Toxic Substances and Disease Registry (ATSDR). 1991. Toxicological profile for trichloroethylene. Draft Update. October.

ATSDR. 1994. Toxicological profile for 1,2-dichloroethene. Draft Update. August.

Massachusetts Department of Environmental Protection (MDEP). 1992. Risk assessment shortform - residential exposure scenario, user's guide. October.

U.S. Environmental Protection Agency (USEPA). 1980. Ambient water quality criteria for trichloroethylene. EPA 440/5-80-077.

USEPA. 1983. Health assessment documents for trichloroethylene. EPA 600/8-82-00666.

USEPA. 1984. Health effects assessment for trichloroethylene. ECAO-CIN-H046.

USEPA. 1987. Health advisories for 25 organics. PB87-235578. March.

USEPA. 2004. Online integrated risk information system (IRIS) .