Response to "Alternative models for carcinogenicity testing: weight of evidence across models" Sam Cohen, Toxicologic Pathology (2001) 29(suppl.): 183-190.

Abstract

In the afore mentioned article, Cohen discusses the alternative models for carcinogenicity testing that were evaluated under the auspices of the Health and Environmental Sciences Institute (HESI) branch of the International Life Sciences Institute (ILSI). The assays included numerous transgenic in vivo models, and the in vitro Syrian Hamster Embryo Cell (SHE) transformation model. Cohen concluded that the SHE model “does not provide a useful discriminatory assay for utilization in the risk evaluation process” Cohen’s statement appears to be based on two inaccurate conclusions, that the SHE assay “does not appear to have discriminatory capabilities with respect to genotoxic versus nongenotoxic chemicals or for rodent carcinogens versus noncarcinogens.” We would like to briey address the two elements of this statement, namely the lack of discrimination of genotoxic from nongenotoxic chemicals, and the lack of discrimination of rodent carcinogens from noncarcinogens by the SHE assay. Finally, we would like to put Cohen’s statement into the context of the substantial literature supporting the value of the SHE assay in the evaluation of a chemical’s carcinogenic potential, a component of the overall risk evaluation process. With regards to the SHE assay lacking the ability to discriminate rodent carcinogens from noncarcinogens, Cohen’s statement is incorrect. As discussed in Mauthe et al (2001) in this same issue, for the speciŽc chemicals evaluated in the ILSI study, the SHE assay correctly identiŽed 94% (15/16) of the rodent carcinogens and 67% (2/3) of the rodent noncarcinogens. This high level of overall concordance (89%) between the SHE assay and results of the two year bioassay in rodents observed in the ILSI study is in agreement with results from the SHE assay with much larger datasets (over