United States Environmental Protection Agency Environmental Criteria and Assessment Office Research Triangle Park NC 27711 Research and Development EPA/600/S8-82/003F Sept. 1985 Project Summary Health Assessment Document for 1,1,1 -Trichloroethane (Methyl Chloroform) Methyl chloroform (MC) is a volatile chlorinated hydrocarbon used exten- sively as an industrial solvent and in consumer products. It has been detect- ed in the ambient air of a variety of urban and non-urban areas of the Unit- ed States. Normally, background levels are in the range of 0.1 to 0.2 ppb (0.54 x 10'3 to 1.08 x 10"3 mg/m3). Levels in some urban areas have ranged up to 20 ppb (0.11 mg/m3). MC has been less frequently detected in water, generally at levels of 1 ppb or less. In certain instances involving contamination of groundwater, much higher levels have been reported. The weight of available evidence obtained from both human and animal data suggests that long-term exposure to environmental levels of MC poses no serious health concern to the general population. However, the available data are inadequate for classifying the mut- agenic and carcinogenic potential for MC. The no-observed-effect level (NOEL*) for short-term exposure of humans is in the range of 350 to 500 ppm (1,890 to 2,700 mg/m3). This Project Summary was developed by EPA's Office of Health and Environ- mental A ssessment. En vironmental Cri- teria and Assessment Office, Research Triangle Park, NC, to announce key findings of the research project that is fully documented in a separate report of the same title (see Project Report order- ing information at back). "NOEL (no-observed-effect level) the lowest expo- sure level at which there are no statistically signif- icant increases in frequency or seventy of effects between the exposed population and its appropriate control Introduction 1,1,1-Trichloroethane (methyl chloro- form, MC) is a volatile chlorinated hydro- carbon. Since its commercial introduc- tion, MC has been used increasingly as an industrial solvent and in consumer products such as spot removers. Produc- tion of MC in the United States is esti- mated to have increased from 121,000 metric tons in 1970 to 315,000 in 1980. About 88 percent of annual production in the United States is released largely to the atmosphere through dispersive use. There are no known natural sources of emissions of MC. Methyl chloroform has been detected in the ambient (natural environment) air of a variety of urban and non-urban areas of the United States and other regions of the world. Levels range from trace amounts in rural areas to about 20 parts per billion (ppb) or 0.108 mg/m3 in some large urban centers. Normally, back- ground levels of MC are in the range of 0.1 to 0.2 ppb (0.54 x 10'3 to 1.08 x 10"3 mg/m3). Less frequently has MC been detected in water. It is not soluble to any appreciable extent but in some surface and drinking waters has been monitored at levels of 1 ppb or less. In certain instan- ces involving contamination of ground- water, much higher levels have been reported. In the troposphere, a region of the atmosphere extending from ground level to as high as 15 kilometers, MC is removed to a substantial extent through reaction with hydroxyl radicals. Based on current knowledge of its reaction kinet- ics, the lifetime of MC in the troposphere is in the range of 5 to 10 years. This time period permits a portion of the MC to be ------- conveyed to the stratosphere where, along with other compounds, it may par- ticipate in ozone (Os) destruction path- ways. MC and other compounds that add to the chlorine burden in the stratosphere may contribute to the effects of global Oa depletion. Occurrence of such depletion could result in an increased incidence of non-malignant forms of skin cancer due to increases in the amount of biologically damaging radiation reaching the earth's surface.The extent to which past, current, and future emissions of MC contribute to O3 depletion can be realistically estimated only by assessing the interrelationships between all the principal reactions in- volved in both the formation and destruc- tion of atmospheric Oa. The extent and direction to which actual global Os levels have changed over the years can not be estimated with available measurement methods. Exposure and Effects Because MC is primarily an air contam- inant, inhalation is the principal and most rapid route of exposure. An 8-hour expo- sure to theTWA** of 350 parts per million (ppm) or 1,890 mg/m3 is estimated to result in about two grams of MC absorbed into the body of an average-sized 70 kg man. The total amount absorbed increas- es in direct proportion to inspired air con- centrations and to the length of exposure and physical activity. Once body equilib- rium or steady-state has been attained, no further uptake is possible. There is strong evidence that MC will partition selectively into lipid-tissues upon chronic or long-term exposure to even low ambi- ent air concentrations, until steady-state is attained. Because of its lipophilic nature, MC is expected to cross mem- brane barriers in the body and diffuse into the brain and the colostrum of nursing mothers, as well as into the fetus during pregnancy. Unlike other chlorinated sol- vents such as trichloro- and tetrachlo- roethylene, MC is only metabolized in humans toa limited extent, about six per- cent or less of the total retained dose. Although metabolism of MC is affected by other chemicals and drugs, there is no evidence that it enhances its own metab- olism. The primary route of elimination from the body is via the lungs, through which MC is exhaled in unchanged form along with a metabolite, carbon dioxide. The only identified urinary metabolites are trichloroethanol and trichloroacetic acid. Based on presently available data, the likelihood of adverse health effects result- ing from chronic exposure to the ambient air levels commonly encountered appears to be extremely low. Although the availa- ble health data are inadequate to classify MC's mutagenic and carcinogenic poten- tial, if any, the NOEL for short-term expo- sure of humans to MC is estimated to be in the range of approximately 350 to 500 ppm (1,890 to 2,700 mg/m3). This NOEL is many orders of magnitude higher than the highest levels of MC (20 ppb; 0.108 mg/3) measured in the ambient air of urban areas. Based upon available human data, the estimated relationship between acute effects and single short-time expo- sures is as follows: Exposure 100 ppm (540 mg/m') 350 - 500 ppm (1,890-2,700 mg/m3) 1,000 ppm (5,400 mg/m3) 1,900-2,650 ppm (10,260-14,310 mg/m3) > 5,000 ppm (27,000 mg/m3) Acute Effect Apparent odor threshold Obvious odor, slight changes in perception Disturbance of equilibrium Lightheadedness, irritation of the throat Onset of narcosis "TWA (Time Weighted Average)'the time-weighted average concentration for a normal 8-hour work- day and a 40-hour workweek to which nearly all workers may be exposed repeatedly, day after day, without adverse effect In the range of the NOEL, no significant abnormal blood chemistry or organ func- tion decrements have been noted. Symp- toms of neurological dysfunction were observed at higher exposure levels. These symptoms were qualitatively diagnosed by the subjects' impaired performance of clinical-level cognitive and manual tasks. More extensive human and laboratory animal data are needed before firm con- clusions about adverse health responses to low-level exposures to MC can be drawn. Similarly, MC has not demonstrated any teratogenic potential in the studies conducted to date in rodent species. Commercially available samples of MC are genotoxic to mouse hepatocytes and are weakly mutagenic in Salmonella under treatment conditions where suffi- cient exposure is ensured. The available data are inadequate, however, for reach- ing firm conclusions regarding the ability of MC to cause gene mutations in other organisms; however, the possibility that this substance, its associated stabilizing materials, or its metabolites may have mutagenic effects in humans has not been eliminated. On the basis of animal bioassays per- formed to date and in the absence of epidemiological information, it is not pos- sible to classify MC as to its carcinogenic potential in humans. Recommendations for Further Studies Although the available human and tox- icity data indicate that ambient exposure to MC is not currently a human health concern, it is apparent that further invest- igation is needed in several areas. Areas in which incomplete information is avail- able, and that should be considered when formulating research needs, are present- ed below, not necessarily in order of priority. 1. Neurobehavioral Toxicity. Few an- imal studies have been made of the effects of MC on the nervous sys- tem and behavior. Most endpoints studied have been relatively insen- sitive. Further studies on more sen- sitive endpoints are needed. 2. Teratogenicity and Reproductive Effects. Published data on three- generation animal studies via inha- lation do not adequately assess the teratogenic and reproductive effects potential of MC. 3. Mutagenicity. In order to determine conclusively the mutagenic poten- tial of MC, pure MC should be tested in studies appropriately de- signed to ensure exposure of the indicator organism. 4. Carcinogen/city. In order to deter- mine more effectively the human carcinogenic potential of MC, life- time inhalation studies in appro- priate rodent species should be undertaken. ------- This Project Summary was prepared by staff of Environmental Criteria and Assessment Office, U.S. Environmental Protection Agency. Research Triangle Park. NC 27711. Mark Greenberg is the EPA Project Officer (see below). The complete report, entitled "Health Assessment Document for 1,1,1-Trichloro- ethanefMethylChloroform),"(OrderNo. PB84-183565; Cost: $17.50, subject to change) will be available only from: National Technical Information Service 5285 Port Royal Road Springfield, VA22161 Telephone: 703-487-4650 The EPA Project Officer can be contacted at: Environmental Criteria and Assessment Office U.S. Environmental Protection Agency Research Triangle Park, NC 27711 United States Environmental Protection Agency Center for Environmental Research Information Cincinnati OH 45268 Official Business Penalty for Private Use $300 0000329 PS U S ENVIR PROTECTION AGENCY CHICAGO ------- |