Uptake, tissue distribution, and fate of inhaled carbon tetrachloride: Comparison of rat, mouse, and hamster

Carbon tetrachloride is hepatotoxic in rats, mice, and hamsters. However, r ats are less sensitive to the hepatotoxic effects of CCl4 than the other tw o species. The purpose of this study was to compare the uptake, tissue dist ribution, and elimination of CCl4 by these three rodent species. Groups of 20 F344/Crl BR rats, B6C3F(1) mice, and Syrian hamsters were exposed by nos e-only inhalation for 4 h to 20 ppm C-14-labeled CCl4. The fate of C-14 was followed in tissues, excreta, and exhaled breath for 48 h after the exposu re. 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 followin g species ranking: mouse > hamster > rat. Patterns of CE elimination were s pecies and tissue dependent, with the majority of elimination occurring wit hin 48 h after exposure. Rats eliminated less radioactivity associated with metabolism ( (CO2)-C-14, urine and feces) and more radioactivity associate d with parent compound ( exhaled activity trapped on charcoal) than did mic e or hamsters. The results indicate that ranking of species sensitivity to the hepatotoxic effects of inhaled CCl4 correlates with CE dose to liver an d with the ability to metabolize CCl4.