Trichloroethylene intermediates

Halogenation and Hydrohalogenation. Halogens add to the triple bond of acetylene. FeCl catalyzes the addition of CI2 to acetylene to form 1,1,2,2-tetrachloroethane which is an intermediate in the production of the industrial solvents 1,2-dichloroethylene, trichloroethylene, and perchloroethylene (see Chlorocarbons and chlorohydrocarbons). Acetylene can be chlorinated to 1,2-dichloroethylene directiy using FeCl as a catalyst... 

Chlorination of various hydrocarbon feedstocks produces many usehil chlorinated solvents, intermediates, and chemical products. The chlorinated derivatives provide a primary method of upgrading the value of industrial chlorine. The principal chlorinated hydrocarbons produced industrially include chloromethane (methyl chloride), dichloromethane (methylene chloride), trichloromethane (chloroform), tetrachloromethane (carbon tetrachloride), chloroethene (vinyl chloride monomer, VCM), 1,1-dichloroethene (vinylidene chloride), 1,1,2-trichloroethene (trichloroethylene), 1,1,2,2-tetrachloroethene (perchloroethylene), mono- and dichloroben2enes, 1,1,1-trichloroethane (methyl chloroform), 1,1,2-trichloroethane, and 1,2-dichloroethane (ethylene dichloride [540-59-0], EDC). 

Ninety-six percent of the EDC produced in the United States is converted to vinyl chloride for the production of poly(vinyl chloride) (PVC) (1) (see Vinyl polymers). Chloroform and carbon tetrachloride are used as chemical intermediates in the manufacture of chlorofluorocarbons (CECs). Methjiene chloride, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene have wide and varied use as solvents. Methyl chloride is used almost exclusively for the manufacture of silicone. Vinylidene chloride is chiefly used to produce poly (vinylidene chloride) copolymers used in household food wraps (see Vinylidene chloride and poly(vinylidene chloride). Chloroben2enes are important chemical intermediates with end use appHcations including disinfectants, thermoplastics, and room deodorants. 

The most important reactions of trichloroethylene are atmospheric oxidation and degradation by aluminum chloride. Atmospheric oxidation is cataly2ed by free radicals and accelerated with heat and with light, especially ultraviolet. The addition of oxygen leads to intermediates (1) and (2). 

In Japan, Toagosei is reported to produce trichloroethylene and tetrachloroethylene by chlorination of ethylene followed by dehydrochlorination. In this process the intermediate tetrachloroethane is either dehydrochlorinated to trichloroethylene or further chlorinated to pentachloroethane [76-01-7] followed by dehydrochlorination to tetrachloroethylene. Partially chlorinated by-products are recycled and by-product HCl is available for other processes. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for trichloroethylene. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancer health effects only and do not reflect a consideration of carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Animal experimentation has revealed inhaled concentrations that result in death following acute, intermediate, and chronic exposure. An LC50 value for acute exposure in rats was reported as 12,500 ppm for a 4-hour exposure (Siegel et al. 1971). Two out of 10 mice died after a 4-hour exposure to 6,400 ppm trichloroethylene (Kylin et al. 1962). Death was often caused by the central nervous system depression that... 

Used to derived an intermediate-duration inhalation Minimal Risk Level (MRL) of 0.1 ppm for trichloroethylene 50 ppm adjusted tor duration (5/7 days x 8 hr/d) and species-specific ratio of daiiy inhalation volume (m /day)/body weight(kg) ratio for rat (0.23/2.17) to human (20/70) to 44.2 ppm, divided by an uncertainty factor of 300 (10 for using a LOAEL, 3 tor extrapolation from animals to humans, and 10 tor human variability) = 0.147 ppm, rounded to 0.1 ppm. 

Inhalation of trichloroethylene for acute or intermediate periods can cause liver enlargement in laboratory animals. Usually this effeet is reversible when exposure eeases. Histological changes were observed in some studies but not in others. Liver weight and plasma butyryleholinesterase (BuChE) aetivity were increased in various strains of mice exposed to 37-300 ppm eontinuously for 30 days (Kjellstrand et al. 1983a, 1983b). 

Body Weight Effects. Body weight loss has been reported in humans occupationally exposed to trichloroethylene for intermediate or chronic durations at concentrations resulting in neurological effects (Mitchell and Parsons-Smith 1969 Schattner and Malnick 1990). 

After 10 days of exposure, reduced social behavior and reduced exploratory behavior were observed in rats exposed to 100 ppm trichloroethylene 6 hours per day 5 days per week for a total of 5 weeks (Silverman and Williams 1975). In rats exposed to 50 or 100 ppm trichloroethylene 8 hours/day, 5 days/week for 6 weeks, effects on sleep patterns were observed (Arito et al. 1994a). At 50 ppm decreased wakefulness was observed during the exposure. Effects remaining at 22 hours after the end of the 6-week exposure included decreased heart rate during sleep at 50 ppm and decreased wakefulness after exposure of 100 ppm (Arito et al. 1994a). Based on the 50-ppm LOAEL identified in the Arito et al. (1994a) study, an intermediate-duration inhalation MRL of 0.1 ppm was calculated as described in the footnote in Table 2-1. 

Histopathological changes in the lungs have not been observed in other intermediate- and chronic-duration studies of rats or mice orally exposed to trichloroethylene (Maltoni et al. 1986 NCI 1976 NTP 1988, 1990). The maximum doses used in these studies were 3,000 mg/kg/day for an intermediate-duration study in mice (NTP 1990), and 1,097 mg/kg/day for a chronic-duration study in rats (NCI 1976). 

Adrenal gland weights were not affected in rats treated by gavage with 1,500 mg/kg/day trichloroethylene in com oil for 14 days (Berman et al. 1995). Histopathological changes in endocrine glands (thyroid, parathyroid, pancreas, adrenals, pituitary) have not been observed in rats or mice exposed by gavage to trichloroethylene in oil for intermediate or chronic durations (Maltoni et al. 1986 NCI 1976 NIP 1988, 1990). 

An MRL of 0.1 ppm was derived for intermediate inhalation exposure (15-364 days) to trichloroethylene. This MRL was based on a study by Arito et al. (1994a) in which male JCL-Wistar rats were exposed to 0, 50, 100, or 300 ppm trichloroethylene for 6 weeks, 5 days/week, 8 hours/day. A LOAEL of 50 ppm was observed for decreased wakefulness during exposure, and decreased postexposure heart rate and slow wave sleep. Another study with rats found an increase in sleep-apneic episodes and cardiac arrhythmias after exposure to trichloroethylene (Arito et al. 1993). These results corroborate similar effects observed in humans exposed to trichloroethylene, as described in the previous paragraph, as well as evidence of organic solvent-induced sleep apnea in humans (Edling et al. 1993 Monstad et al. 1987, 1992 Wise et al. 1983). 

No intermediate oral exposure MRL was derived for trichloroethylene because of a lack of adequately designed studies examining suitable end points. No chronic oral exposure MRL was derived for trichloroethylene because the existing studies had end points that were not suitable for derivation of an MRL. 

Animals have also died following large inhalation (Kylin et al. 1962 Siegel et al. 1971) or oral exposures (Merrick et al. 1989 Smyth et al. 1969 Tucker et al. 1982). Deaths in animals have also been reported following chronic-duration inhalation exposure (Henschler et al. 1980) and following intermediate- and chronic-duration oral exposure (Henschler et al. 1984 NCI 1976 NTP 1990). No deaths due to dermal exposure have been reported. Death is not likely to result from exposure to low levels of trichloroethylene at hazardous waste sites. 

Dermal Effects. Some humans experienced dry throats following acute inhalation exposure to trichloroethylene at 200 ppm (Stewart et al. 1970). Persons working with trichloroethylene for intermediate periods sometimes develop skin rashes and dermatitis (Bauer and Rabens 1974 El Ghawabi et al. 1973). It is reported that some people may be particularly sensitive to trichloroethylene and develop allergies when exposed to high levels in the air or on their skin during oeeupational exposures of intermediate duration (Cziijak et al. 1993 Goh and Ng 1988 Nakayama et al. 1988 Phoon et al. 1984). Exposure to... 

With the exception of studies examining reproductive outcome in people exposed to trichloroethylene in drinking water (ATSDR 1997 MDPH 1994), intermediate-duration studies in humans following oral exposure were not available. Intermediate-duration oral studies of trichloroethylene in animals (Barret et al. 1991, 1992 Buben and O Flaherty 1985 Constan et al. 1995 Dawson et al. 1993 Goel et al. 1992 Isaacson et al. 1990 Mason et al. 1984 Merrick et al. 1989 NCI 1976 NTP 1988, 1990 Stott et al. 1982 Tucker et al. 1982 Zenick et al. 1984) are available, but did not adequately provide exposure levels that could be... 

Additional animal studies of trichloroethylene following intermediate-duration oral exposure are necessary to further define dose-response relationships. Because developmental neurotoxicity appears to be a sensitive end point, a focus on this end point would be useful. Animals studies following intermediate-duration dermal exposure are necessary. These studies would indicate whether targets following dermal exposure differ compared to inhalation and oral exposure. 

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