National Industrial Chemicals Notification and Assessment Scheme
Effects on Experimental Animals and in vitro Test Systems
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- 10.1Acute toxicity
- 10.2Irritation and corrosivity
- 10.2.2Eye
- 10.3Sensitisation
10.Effects on Experimental Animals and in vitro Test SystemsNumerous reviews of the health effects of trichloroethylene have been conducted. No additional toxicity data was provided by applicants. For the genotoxicity and carcinogenicity endpoints a different approach was taken acknowledging the contentious interpretation of many of the available studies. For these endpoints individual studies which were in contention were reviewed together with views of other authorities. 10.1Acute toxicityTrichloroethylene has low acute toxicity by all routes of exposure. The LC50 and LD50 values in various animals are shown in Table 21. The lowest LC50 in rats is 4800 ppm for 4 h and 5857ppm in mice following 6 h exposure. Table 21- LC50 and LD50 values for trichloroethylene
The major acute toxic effects in animals are consistent with the findings in humans. The main signs of acute toxicity in rats and mice were those of CNS depression such as stupor and poor coordination and respiratory failure. Irritation of the eyes and respiratory tract were also reported. Effects on the liver, indicated by transient increases in serum ALT and AST, were reported following oral administration. Species specific toxicity has been noted since pulmonary toxicity has been observed in mice but not in rats. A dose dependent increase in the number of vacuolated Clara cells was seen in mice following single inhalation exposures between 20 and 2000 ppm of trichloroethylene for 6 h. At higher dose levels pyknosis and focal loss of bronchiolar epithelium were observed. Other cell types were not affected (Odum et al., 1992).
10.2.1SkinSeveral studies in animals, guinea pigs and rabbits, using occluded and non occluded dressing indicate that trichloroethylene is irritating to the skin. (Smyth et al., 1969; Duprat et al., 1976; Wahlberg, 1984; Anderson et al., 1986). 10.2.2EyeAnimal studies provide limited information on eye irritation. No animal tests complying with standard protocols for detecting eye effects of trichloroethylene have been reported. Two studies reported corneal abrasions and necrosis of the cornea following instillation of trichloroethylene into rabbit eyes (Smyth et al., 1969; Duprat et al., 1976). 10.3SensitisationNo skin or respiratory sensitisation studies have been conducted in animals. 10.4Repeated dose toxicityMany repeated dose studies (inhalation and oral) have been conducted in a range of species. The results of the major studies are summarised in Table 22. The main toxic effects following repeated exposure of animals by the inhalation and oral route are on the liver and kidneys. Adverse effects were also seen on hearing, the lungs and the nervous system following inhalation exposure. Studies reported animals surviving repeated inhalation exposure to between 1000 and 7000 ppm for 90 days. No Observed Adverse Effect Levels (NOAEL) have been identified for effects of trichloroethylene on the various systems in animals. The kidneys appear to be the most sensitive organs in animals. Kidney effects were observed in male rats following inhalation, and in both rats and mice in both sexes after oral exposure. In a 2-year inhalation study using rats, meganucleocytosis of the renal tubules was reported at 300 ppm (LOAEL) in male rats with no effects being seen at 100 ppm (0.55mg/L) (NOAEL) (Maltoni et al., 1988). Meganucleocytosis was also reported in an oral study at 250 mg/kg bw/day in rats with a NOAEL of 50 mg/kg bw/day (Maltoni et al., 1986). In mice, renal cytomegaly was observed in both sexes following oral administration of 1000 mg/kg bw/day for 2 years (US National Toxicology Program NTP, 1990) Trichloroethylene-induced liver effects have been reported in mice and rats, with mice being more sensitive than rats. Increased liver weight, AST and ALT levels and cytochrome P-450 activities have been noted. At very high doses centrilobular cell enlargement and necrosis have been observed following inhalation and oral exposure. Peroxisome proliferation has been observed in the mouse liver but not in rats. NOAELs identified for liver effects are 200 ppm (inhalation) in both rats and rabbits (Adams et al., 1951) and 375 mg/kg/day and 500 mg/kg/day (oral) for mice and rats respectively. Evidence of neurotoxicity, such as increased activity and ototoxicity was also reported in animals. Simultaneous exposure to two solvents, styrene and trichloroethylene did not produce a greater hearing loss than from exposure to either solvent alone (Rebert et al., 1993). Pulmonary toxicity was reported in mice following repeated inhalation exposure to 450 ppm trichloroethylene for two weeks. Vacuolation of Clara cells was observed following exposure on the first day, however the lungs returned to normal after 4 or 5 consecutive exposures. The Clara cell lesions were observed again after a 2-day break from exposure to trichloroethylene. It is likely that restoration of the non-ciliated cells occurs (Odum et al, 1992).  
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