Final Report on the Safety Assessment of Trichloroethane

Abstract

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 chromatography, 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 LD50 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 findings 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 Trichloroethane applied to the clipped backs of guinea pigs produced histopathologic 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 μM, was not mutagenic using the mouse lymphoma assay at up to 0.51 μg/ml, was equivocal in that assay when tested with S9, and was also equivocal in a sister-chromatid exchange assay using Chinese hamster ovarian (CHO) cells with and without S9. Mice ingesting 80,000 ppm Trichloroethane in their drinking water had an increase in the frequency of micronucleated normochromatic erythrocytes. A peripheral blood micronucleus test in female mice was negative. Trichloroethane was not carcinogenic to rats when administered 1500 mg/kg by oral gavage 5 days/week for 78 weeks or in mice administered 6000 mg/kg. Exposure to 1500 ppm Trichloroethane vapor for 6 h/day, 5 days/week for 2 years likewise gave no indications of oncogenic effects in rats or mice. People who have been exposed to Trichloroethane have reported dizziness, lassitude, unconsciousness, respiratory depression, peripheral vascular collapse, impaired postural control, mild encephalopathy, perioral tingling, burning on the tongue and discomfort in the hands and feet. The Cosmetic Ingredient Review (CIR) Expert Panel recognizes that Trichloroethane (1,1,1-Trichloroethane) has been declared a Class I ozone-depleting substance by the EPA and its use is limited to essential products. The FDA has determined that use of Trichloroethane in aerosol cosmetic products is considered nonessential. At issue for this assessment is the safety of direct exposure to individuals as a result of exposure to cosmetic products that may contain Trichloroethane. The Expert Panel found the available data to be sufficient to support the safety of Trichloroethane as a solvent in cosmetic products.