1,1,2-trichloroethylene toxicity

The liver is an organ that shows variable effects from trichloroethylene among species, and this can probably be attributed to interspecies differences in metabolism (see Section 2.4.2.1). Specifically, the apparent difference in susceptibility to trichloroethylene-induced hepatocellular carcinoma between humans and rodents may be due to metabolic differences (see Section 2.4.2.3). Kidney effects are also variable among species. Humans and mice are less sensitive than rats. In rats exposed chronically to trichloroethylene, toxic nephrosis characterized as cytomegaly has been reported (NTP 1988). The kidney effects in rats do not seem to be related to an increase in alpha-2 -globulin (Goldsworthy et al. 1988). Effects on the nervous system appear to be widespread among species, presumably due to interactions between trichloroethylene and neuronal membranes. 

Comparative Toxicokinetics. In humans, the targets for trichloroethylene toxicity are the liver, kidney, cardiovascular system, and nervous system. Experimental animal studies support this conclusion, although the susceptibilities of some targets, such as the liver, appear to differ between rats and mice. The fact that these two species could exhibit such different effects allows us to question which species is an appropriate model for humans. A similar situation occurred in the cancer studies, where results in rats and mice had different outcomes. The critical issue appears to be differences in metabolism of trichloroethylene across species (Andersen et al. 1980 Buben and O Flaherty 1985 Filser and Bolt 1979 Prout et al. 1985 Stott et al. 1982). Further studies relating the metabolism of humans to those of rats and mice are needed to confirm the basis for differences in species and sex susceptibility to trichloroethylene s toxic effects and in estimating human heath effects from animal data. Development and validation of PBPK models is one approach to interspecies comparisons of data. 

Bauer M, Rabens SF. 1974. Cutaneous manifestations of trichloroethylene toxicity. Arch Dermatol 110 886-890. 

Goh CL, Ng SK. 1988. A cutaneous manifestation of trichloroethylene toxicity. Contact Dermatitis 18 59-61. 

Kleinfeld M, Tabershaw IR. 1954. Trichloroethylene toxicity Report of five fatal cases. Arch hid Hyg Occup Med 10 134-141. 

Henry, S. Grbic-Galic, D. (1991 ) Influence of endogenous and exogenous electron donors and trichloroethylene toxicity on trichloroethylene oxidation by methanotrophic cultures from a groundwater aquifer. Applied and Environmental Microbiology, 57, 236-44. 

Goh and Ng (1988) reported of a patient with recurrent localized erythematous xerotic plaques, which became parched and fissured on the arms and trunk of a patient with trichloroethylene. Biopsy showed superficial perivascular lymphohistiocytic infiltrate. The epidermis shows parakeratosis. The route of entry of trichloroethylene was from the respiratory tract and it was believed to be a form of systemic trichloroethylene toxicity in a sensitized individual. 

Batschvaros B, Minkow DM (1968) Dermatitis and purpura from rubber in clothing. Trans St John s Hospit Derm Soc 54 73-78 Bauer M, Rabens SF (1977) Trichloroethylene toxicity. Int J Dermatol 16 113-116... 

Goh CL, Kwok SF, Rajan VS (1984) Cross sensitivity in color developers. Contact Dermatitis 10 280-285 Goh CL, Ng SK (1988) A cutaneous manifestation of trichloroethylene toxicity. Contact Dermatitis 18 59-60 Hausen BM (1981) Woods injurious to human health. Walter de Gruyter, Berlin, p 59... 

AH volatile organic solvents are toxic to some degree. Excessive vapor inhalation of the volatile chloriaated solveats, and the central nervous system depression that results, is the greatest hazard for iadustrial use of these solvents. Proper protective equipment and operating procedures permit safe use of solvents such as methylene chloride, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene ia both cold and hot metal-cleaning operations. The toxicity of a solvent cannot be predicted from its chlorine content or chemical stmcture. For example, 1,1,1-trichloroethane is one of the least toxic metal-cleaning solvents and has a recommended threshold limit value (TLV) of 350 ppm. However, the 1,1,2-trichloroethane isomer is one of the more toxic chloriaated hydrocarboas, with a TLV of only 10 ppm. 

Inhibited grades of 1,1,1-trichloroethane are used in hundreds of different industrial cleaning appHcations. 1,1,1-Trichloroethane is preferred over trichloroethylene or tetrachloroethylene because of its lower toxicity. Additional advantages of 1,1,1-trichloroethane include optimum solvency, good evaporation rate, and no fire or flash point as determined by standard test methods. Common uses include cleaning of electrical equipment, motors, electronic components and instmments, missile hardware, paint masks, photographic film, printed ckcuit boards, and various metal and certain plastic components during manufacture (see Metal surface treatments). 

The only significant use of 1,1,2,2-tetrachloroethane is as a feedstock in the manufacture of trichloroethylene, tetrachloroethylene, and 1,2-dichloroethylene. Although it is an excellent solvent, its use should be discouraged in view of its high toxicity. 

Trichloroethylene [79-01-6J, trichloroethene, CHCL=CCL2, commonly called "tri," is a colorless, sweet smelling (chloroformlike odor), volatile Hquid and a powerhil solvent for a large number of natural and synthetic substances. It is nonflammable under conditions of recommended use. In the absence of stabilizers, it is slowly decomposed (autoxidized) by air. The oxidation products are acidic and corrosive. Stabilizers are added to all commercial grades. Trichloroethylene is moderately toxic and has narcotic properties. 

Trichloroethylene is acutely toxic, primarily because of its anesthetic effect on the central nervous system. Exposure to high vapor concentrations is likely to cause headache, vertigo, tremors, nausea and vomiting, fatigue, intoxication, unconsciousness, and even death. Because it is widely used, its physiological effects have been extensively studied. 

The trichloroethylene is oxidized, the gaseous products are removed by the flowing air, and the ehlorine is eaptured by the solid soda and forms salt. The solid salt is removed by diseharging the used OXITOX at the bottom of the reaetor. This is a relatively slow reaetion and the central interest is in removing the last traees of toxic chlorinated compounds (for which TCE is only a model eompound), therefore a very simple model was used. Based on conservation prineiples, it was assumed that chloride removed from the gas phase ends up in the solid phase. This was proven in several material balanee ealeulations. No HCl or other ehlorinated compound was found in the gas phase. The eonsumption rate for TCE was expressed as ... 

Decomposition of trichloroethylene can occur upon contact with naked flames, red-hot surfaces, hot elements of electric heaters, or intense UV light with the generation of acidic and highly-toxic products. The presence of reactive contaminants, e.g. acids, strong alkalis, highly-reactive metals, may also result in decomposition to similar products. 

NOTE - Petrochemical plants also generate significant amounts of solid wastes and sludges, some of which may be considered hazardous because of the presence of toxic organics and heavy metals. Spent caustic and other hazardous wastes may be generated in significant quantities examples are distillation residues associated with units handling acetaldehyde, acetonitrile, benzyl chloride, carbon tetrachloride, cumene, phthallic anhydride, nitrobenzene, methyl ethyl pyridine, toluene diisocyanate, trichloroethane, trichloroethylene, perchloro-ethylene, aniline, chlorobenzenes, dimethyl hydrazine, ethylene dibromide, toluenediamine, epichlorohydrin, ethyl chloride, ethylene dichloride, and vinyl chloride. 

Halogenated hydrocarbons depress cardiac contractility, decrease heart rate, and inhibit conductivity in the cardiac conducting system. The cardiac-toxicity of these compounds is related to the number of halogen atoms it increases first as the number of halogen atoms increases, but decreases after achieving the maximum toxicity when four halogen atoms are present. Some of these compounds, e.g., chloroform, carbon tetrachloride, and trichloroethylene, sensitize the heart to catecholamines (adrenaline and noradrenaline) and thus increase the risk of cardiac arrhythmia. 

The ideal disposal method is a chemical treatment that can convert hazardous waste into environmentally benign materials. For example, trichloroethylene (CI2 C I CHCl) is highly toxic to aquatic life, but this compound can be made nontoxic by chemical treatment that converts its chlorine atoms into chloride anions. Similarly, the chromium-containing waste from electroplating operations contains highly toxic CrOq anions, but a chemical treatment that converts CrOq into Cr causes the chromium to precipitate from the solution as insoluble Cr (OH). This removal of chromium detoxifies the water. 

Both these conversion processes involve the addition of electrons to the toxic substances. The trichloroethylene molecule is electrically neutral and must gain electrons in reactions that generate negatively charged chloride anions, hi addition, water or hydronium ions must supply hydrogen atoms that replace the chlorine atoms in the organic substance. The detailed reaction is complicated, but the net reaction is relatively simple CI2 C I CHCl + 3 H3 + 6 H2 C CH2 + 3 Cr + 3 H2 O... 

These are stringent requirements yet a veiy common material does this job spectacularly well iron filings. Metallic iron contains neutral iron atoms that readily donate electrons to become Fe or Fe cations, neither of which is significantly toxic. Fe Fe + 2 e" Thus, when iron reacts with trichloroethylene or chromate, all the products are relatively non toxic. 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of trichloroethylene. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

Substantial toxic effects in the liver have been seen in acute studies in animals. Prout et al. (1985) administered single doses of 10-2,000 mg/kg trichloroethylene to rats and mice. Blood level kinetics of trichloroethylene and its metabolites revealed that trichloroethylene was metabolized more quickly in the mouse, and thus, at high doses, the mouse was exposed to greater concentrations of trichloroethylene metabolites than the rat. Hepatic hypertrophy and centrilobular swelling were observed in mice treated with... 

Osbome-Mendel rats appeared to be the most sensitive to the renal effeets of trichloroethylene. At a dose of 500 mg/kg/day, toxic nephrosis occurred in 78% of male and 60% of female Osbome-Mendel rats, 37% of male and 45% female ACI rats, 36% of male and 63% of female Marshall rats, and 20% of male and 17% female August rats. Another chronic study revealed renal tubular nucleocytosis in 50% of male rats exposed to 250 mg/kg/day trichloroethylene for 52 weeks by oil gavage (Maltoni et al. 1986). Further explanation of these studies is in Section 2.2.2.8. 

Studies in animals indicate that trichloroethylene can act as a developmental toxicant, especially at doses also resulting in maternal toxicity. Significant decreases in litter size have been reported in rats treated by gavage... 

II. 7%, and 30% of pups from dams treated at 0, 475, 633, 844, and 1,125 mg/kg/day, respectively (Narotsky et al. 1995). In a study in mice that did not use maternally toxic doses, no developmental effects were observed in the offspring of B6C3Fj mice treated by gavage with 240 mg/kg/day trichloroethylene in com oil on gestation days 1-5, 6-10, or 1-15 (Cosby and Dukelow 1992). 

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