Acute, subacute, and subchronic oral toxicity studies of 1,1-dichloroethane in rats: Application to risk evaluation

1,1-Dichloroethane (DCE) is a solvent that is often found as a contaminant of drinking water and a pollutant at hazardous waste sites. Information on its short- and long-term toxicity is so limited that the U.S. EPA and ATSDR have not established oral reference doses or minimal risk levels for the v olatile organic chemical (VOC). The acute oral LD50 in male Sprague-Dawley (S-D) rats was estimated in the present study to be 8.2 g/kg of body weight (bw). Deaths appeared to be due to CNS depression and respiratory failure. In an acute/subacute experiment, male S-D rats were given 0, 1, 2, 4, or 8 g DCE/kg in corn oil by gavage for 1, 5, or 10 consecutive days. The anima ls were housed in metabolism cages for collection of urine and sacrificed f or blood and tissue sampling 24 h after their last dose. There were decreas es in body weight gain and relative liver weight at all dosage levels, as w ell as increased renal nonprotein sulfhydryl levels at 2 and 4 g/kg after 5 and 10 days. Elevated serum enzyme levels, histopathological changes, and abnormal urinalyses were not manifest. For the subchronic study, adult male S-D rats were gavaged with 0.5, 1, 2, or 4 g DCE/kg 5 times weekly for up to 13 weeks. Animals receiving 4 g/kg exhibited pronounced CNS depression, with more than one-half dying by week 11. The 2-g/kg rats exhibited moderat e CNS depression. One 2-g/kg rat died during week 6. There were very few ma nifestations of organ damage in animals that succumbed or in survivors at a ny dosage level. Decreases in bw gain and transient increases in enzymuria were noted at 2 and 4 g/kg. Serum enzyme levels and blood urea nitrogen wer e not elevated, nor were glycosuria or proteinuria present. Chemically indu ced histological changes were not seen in the liver, kidney, lung, brain, a drenal, spleen, stomach, epididymis, or testis. Hepatic microsomal cytochro me P450 experiments revealed that single, high oral doses of DCE did not al ter total P450 levels, but did induce CYP2E1 levels and activity and inhibi t CYP1A1 activity. These effects were reversible and regressed with repeate d DCE exposure. There was no apparent progression of organ damage during th e 13-week subchronic study, nor appearance of adverse effects not seen in t he short-term exposures. One g/kg orally (po) was found to be the acute, su bacute, and subchronic LOAEL for DCE, under the conditions of this investig ation. In each instance, 0.5 g/kg was the NOAEL.