Application of microencapsulation for toxicology studies. II. Toxicity of microencapsulated trichloroethylene in Fischer 344 rats.
Gelatin-sorbitol microcapsules containing 44.1% trichloroethylene (TCE) were prepared and mixed in NIH-07 rodent meal diet and provided at microcapsule concentrations of 0 (untreated control group), 1.25, 2.5, 5.0, or 10% (equivalent to 0, 0.55, 1.10, 2.21, or 4.41% TCE, respectively) to groups of 10 male F344 rats for 14 days. An additional control group received diets containing 5% empty capsules. For comparisons, TCE dissolved in corn oil was administered by gavage to different groups of 10 male rats for 14 consecutive days at dose levels adjusted to correspond to those in the feed study. Treatment-related deaths occurred only in the highest dose group of the gavage study. Body weight gain and feed consumption were reduced in high-dose groups of both the feed and gavage studies. There was no measurable loss of TCE in feed sampled from the cages during the study. Dose-related increases in organ (liver and kidney) weight/body weight ratios, individual cell necrosis in the liver, and hepatic microsomal NADPH cytochrome c reductase and peroxisomal palmitoyl-CoA oxidase and catalase activities were found in both the dosed-fed and gavage groups. Induction of cytochrome P-450 occurred only in the dosed-feed study. There were no significant compound-related pathologic lesions observed in the kidneys, the only other organ examined microscopically. Differences in lethality, cytochrome P-450 levels, and induction of microsomal or peroxisomal enzyme activities were attributed to differences in the method of dosing (gavage versus dosed-feed). The demonstration of no significant loss of TCE from the feed and of similar toxic effects produced by microencapsulated TCE via feed and TCE in corn oil via gavage indicate that microencapsulation can provide an excellent alternative exposure route for studying the oral toxicological properties of volatile chemicals, such as TCE, in rats.
D000821:Animal Feed / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002214:Capsules; D002374:Catalase / Q000378:metabolism; D004355:Drug Stability; D005751:Gastric Lavage; D008297:Male; D008830:Microbodies / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014241:Trichloroethylene / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*
D002214:Capsules; D014241:Trichloroethylene; D010088:Oxidoreductases; D002374:Catalase; C028427:palmitoyl CoA oxidase; D009251:NADPH-Ferrihemoprotein Reductase