transaminase, and aniline hydroxylase activity at all doses. Males had significantly decreased glutathione at the highest dose. In studies with rats, increased relative hepatic weights were observed with cis-1,2-DCE at 32 mg/kg per day and higher (McCauley et al. 1995). Variable changes in hepatic enzyme concentrations were seen, but no histopathologic lesions of the liver. A study of trans-1,2-DCE administered to rats in microcapsules for 14 weeks reported increased hepatic weights in females but not males at 395 mg/kg per day (NTP 2002c). No significant alterations in clinical-chemistry measures were found.

In an inhalation study, fatty degeneration of liver lobules was observed in female rats exposed to trans-1,2-DCE at 200 ppm for 8 or 16 weeks (Freundt et al. 1977).

Renal Toxicity

There is little clinical or histologic evidence of renal toxicity in experimental studies of 1,2-DCE (ATSDR 1996). A recent 14-week study of trans-1,2-DCE reported significantly reduced absolute renal weights in male rats at 1,540 mg/kg per day (NTP 2002c) but no gross or microscopic lesions.

Pulmonary Toxicity

With the exception of some effects on the lungs after lethal doses of trans-1,2-DCE, experimental studies of DCE isomers have yielded little clinical or histologic evidence of pulmonary toxicity (ATSDR 1996).

Reproductive Toxicity

One study of pregnant rats exposed by inhalation to trans-1,2-DCE at 6,000 or 12,000 ppm found a significant increase in the mean number of resorptions per litter (Hurtt et al. 1993), but the authors noted that the value was within the range of historical control values; maternal toxicity was observed. The National Toxicology Program (NTP 2002c) reported no significant changes in sperm motility or vaginal cytology in rats or mice fed microencapsulated trans-1,2-DCE at doses as high as 8,065 mg/kg per day for 14 weeks.

Developmental Toxicity

Hurtt et al. (1993) reported significantly reduced mean combined and female fetal weights in rats exposed to trans-1,2-DCE by inhalation during pregnancy at 12,000 ppm. The dams had frank maternal toxicity, as evidenced by reduced food consumption and reduced weight gain.

Neurotoxicity

Several studies have reported central nervous system (CNS) depression in rats after exposure to cis-1,2-DCE at 878 mg/kg per day (McCauley et al. 1995) or to either isomer of 1,2-DCE at lethal doses (Barnes et al. 1985; McCauley et al. 1995). After inhalation exposure, experimental animals have exhibited lethargy, behavioral changes, and other neurologic effects (ATSDR 1996), but the significance of the changes is unclear. A functional observational battery performed on mice and rats given microencapsulated trans-1,2-DCE in their feed at up to 8,065 mg/kg per day for 14 weeks found no evidence of CNS depression (NTP 2002c).



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