Final Report on the Safety Assessment of Trichloroethane

摘要

Trichloroethane functions in cosmetics as a solvent. Although Trichloroethane has been reported to the Food and Drug Administration (FDA) to be used in cosmetic products, an industry survey found that it is not in current use in the cosmetic industry. Trichloroethane is considered a Class I ozone-depleting substance by the Environmental Protection Agency (EPA) and its use is prohibited in the United States, unless considered essential. The FDA has stated that Trichloroethane's use in cosmetics is considered nonessential. Trichloroethane is detected by gas chromatog-raphy, gas chromatography-mass spectrometry, and gas-liquid chromatography. In rats, Trichloroethane, whether inhaled or injected, is mostly expelled intact from the body through exhalation. A very small percentage is excreted in the urine. In humans, Trichloroethane is rapidly absorbed through the skin and eliminated in exhaled air and a very small percentage is excreted in urine. Inhaled Trichloroethane is eliminated in exhaled air. Acute oral LD_(50) values have been reported as follows: 12.3 g/kg in male rats; 10.3 g/kg in female rats; 11.24 g/kg in female mice; 5.66 g/kg in female rabbits; and 9.47 g/kg in male guinea pigs. Acute toxicity studies using other routes of exposure, including subcutaneous injection and inhalation, produced no evidence of significant toxicity, except at very high exposure levels. Continuous inhalation exposure of rabbits to 750 mg/m3 for 90 days did not produce any signs of toxicity. Continuous exposure of rats, guinea pigs, rabbits, and monkeys to 500 ppm Trichloroethane for 6 months did not produce any signs of toxicity. Other short-term and subchronic inhalation exposures confirmed acute and short-term exposure indings that the toxic effects of inhalation were a function of both concentration and time. Rats receiving 750 or 1500 mg/kg day~(-1) Trichloroethane in corn oil by oral gavage 5 days per week for 78 weeks had reduced body weights and early mortality. Reduced body weights, decreased survival rates, and early mortality (in females) were found in mice dosed with 3000 or 6000 mg/kg day~(-1) (over the last 58 weeks; lower doses were administered for the first 20 weeks). Mice exposed to prolonged periods of Trichloroethane in an inhalation chamber had increased motor activity at levels up to 5000 ppm. Further increase of concentration of exposure resulted in less of an increase of motor activity until motor activity began to fall below normal at 10,000 ppm. Adverse effects on motor activity in rats were seen at exposures as low as 3000 ppm for 4 h. Rabbits had slight reddening and scaling after 10 24-h applications to abdominal skin of Trichloroethane mixed with 2.4% to 3.0% dioxane, and slight to moderate erythema, slight edema, and slight exfoliation was observed when 75% Trichloroethane and 25% tetrachloroethylene were applied to rabbit ears for 11 days. Undiluted Trichloroethaneapplied to the clipped backs of guinea pigs produced histopatho-logic damage in the epidermis. A primary irritation index of 5.22 (out of 8) was reported in rabbits. Trichloroethane applied to the eyes of rabbits resulted in transient irritation and apparent pain, but no corneal damage. There was no effect on gestation, pup survival, or growth in mice given Trichloroethane in drinking water at up to 5.83 mg/ml during mating and/or gestation. Rats exhibited no or minimal effects of ingestion of Trichloroethane up to 30 ppm in drinking water during mating and/or gestation. There was no effect on gestation, pup survival, or growth in mice or rats inhaling 875 ppm Trichloroethane. However, prenatal exposure of rodents to Trichloroethane can produce developmental toxicity in the form of delayed development in the offspring. Trichloroethane has been found to be mutagenic in the Ames assay in some studies and not mutagenic in others. Trichloroethane induced transformations in Fischer rat embryo cell system at 99 muM, was not mutagenic using the mouse lympho