Uptake, Tissue Distribution, and Fate of Inhaled Carbon Tetrachloride: Comparison of Rat, Mouse, and Hamster

Abstract

Carbon tetrachloride is hepatotoxic in rats, mice, and hamsters. However, rats are less sensitive to the hepatotoxic effects of CCl4 than the other two species. The purpose of this study was to compare the uptake, tissue distribution, and elimination of CCl₄ by these three rodent species. Groups of 20 F344/Crl BR rats, B6C3F₁ mice, and Syrian hamsters were exposed by nose-only inhalation for 4 h to 20 ppm ¹⁴C-labeled CCl₄. The fate of ¹⁴C was followed in tissues, excreta, and exhaled breath for 48 h after the exposure. At the end of the exposure, concentrations of CCl₄ equivalents (CE) in tissue were highest in liver of rats and mice, but highest in fat for rats. The liver received the highest dose of CCl₄ equivalents with the following species ranking: mouse > hamster > rat. Patterns of CE elimination were species and tissue dependent, with the majority of elimination occurring within 48 h after exposure. Rats eliminated less radioactivity associated with metabolism (¹⁴CO₂, urine and feces) and more radioactivity associated with parent compound (exhaled activity trapped on charcoal) than did mice or hamsters. The results indicate that ranking of species sensitivity to the hepatotoxic effects of inhaled CCl₄ correlates with CE dose to liver and with the ability to metabolize CCl₄.