Toxicity Studies of p-Chloro-alpha, alpha, alpha-Trifluorotoluene (CAS No. 98-56-6) Administered in Corn Oil and alpha-Cyclodextrin to F344/N Rats and B6C3F1 Mice in 14-Day Comparative Gavage Studies.

摘要

p-Chloro-alpha,alpha,alpha-trifluorotoluene (CTFT) is a volatile, aromatic liquid used as a chemical intermediate in the manufacture of dinitroaniline herbicides. To evaluate the toxicity of CTFT, groups of F344/N rats and B6C3F1 mice of each sex were administered CTFT by gavage once a day for 14 consecutive days in either corn oil or in an experimental molecular complex vehicle, alpha-cyclodextrin (alpha-CD). Dose levels selected for CTFT with the alpha-CD vehicle were 10, 50, and 400 mg/kg; dose levels used with the corn oil vehicle were 10, 50, 400, and 1000 mg/kg. The toxicokinetics of CTFT also were compared by gavage with the different vehicles and by i.v. administration. In genetic toxicity studies, CTFT was not mutagenic in Salmonella typhimurium. These studies demonstrated that oral doses of CTFT of 400 mg/kg or higher caused liver hypertrophy in rats and mice and adrenal changes in rats. Doses of 50 mg/kg or higher caused 'hyaline droplet nephropathy' in male rats. The results were similar with CTFT administered either in corn oil or in alpha-CD (although absorption of CTFT was somewhat more rapid with alpha-CD), suggesting that alpha-CD may be an appropriate vehicle for toxicity studies with other chemicals.