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Transgenic rodent gene mutation models provide quick and statistically reliable assays for mutations in the DNA from any tissue. For regulatory applications, assays should be based on neutral genes, be generally available in several laboratories, and be readily transferable. Five or fewer repeated treatments are inadequate to conclude that a compound is negative but more than 90 daily treatments may risk complications. A sampling time of 35 days is suitable for most tissues and chemicals, while shorter sampling times might be appropriate for highly proliferative tissues. For phage‐based assays, 5 to 10 animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of ∼3 × 10−5 mutants/locus and 125,000–300,000 plaque or colony forming units (PFU or CFU) per tissue. Data should be generated for two dose groups but three should be treated, at the maximum tolerated dose (MTD), two‐thirds the MTD, and one‐third the MTD. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a block design and the total number of PFUs or CFUs and the MF for each tissue and animal reported. Sequencing data would not normally be required but might provide useful additional information in specific circumstances. Statistical tests used should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose‐response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is statistically nonsignificant with all mean MF within two standard deviations of the control. Environ. Mol. Mutagen. 35:253–259, 2000 © 2000 Wiley‐Liss, Inc.

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A comparison of the generation and detoxification of reactive aflatoxin B1 metabolites in different species may elucidate why animal species vary widely in sensitivity to aflatoxin B1 carcinogenicity, in addition to offering some perspective on how sensitive man may be to the carcinogenic effects of this mycotoxin. Scientific literature comparing the ability of cellular fractions from different species to metabolize aflatoxin B1 is reviewed. However, in vitro studies exclude components for multiple metabolic pathways, eliminating the possibility of competition between metabolic activation and detoxification. Quantification of metabolic activation by different species from these studies is therefore limited. The species-specific carcinogenic potency of aflatoxin B1 may be reflected in levels of aflatoxin B1-DNA adducts generated in vivo. The current paucity of quantitative information on human DNA adduct levels does not permit comparisons between different species on this basis.