Pathology-based Evaluation of Chemical Toxicity in the National Toxicology Program and Development of Toxicological Testing Methods for Human Risk Assessment: Carcinogenicity Studies of Dioxin and Dioxin-like Chemicals

초록

Pathological data sets are critical for evaluation of carcinogenicity of chemicals in the preclinical studiesusing laboratory animals. Proper diagnosis and interpretation of non-neoplastic and neoplastic lesions, nomatter what they are spontaneously developed or chemically induced, are prerequisite for determinationof chemical carcinogenicity. The pathology-based criteria have been developed to evaluate thecarcinogenic activity of chemicals; two positive results (clear evidence and some evidence), one uncertainfinding (equivocal evidence), no observable effect (no evidence), and inadequate study. However, thereare lots of things that we need to consider before determination of carcinogenic activity of chemicals suchas adequacy of the experimental design and conduct, common and uncommon neoplasia, progressionfrom benign to malignant neoplasia as well as from preneoplastic to neoplastic lesions, combining benignand malignant tumor incidence in the same organs, multiplicity in site-specific neoplasia, doserelationship, statistical significance of the observed tumor increase, concurrent control tumor incidencesas well as historical control rate for a specific neoplasm, etc. In the present study, we introduce thecarcinogenicity studies of dioxin and dioxin-like chemicals which had been performed as NationalToxicology Program (NTP) in the USA for years, and discuss the pathology data-based approachingstrategy for determination of carcinogenic activity of chemicals.

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