2,3,7,8-Tetrachlorodibenzo-p-dioxin mechanistic data and risk assessment: gene regulation, cytotoxicity, enhanced cell proliferation, and tumor promotion.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been found to cause several tumor types in rodents, but TCDD has not been proven to cause cancer in humans, although there have been reported associations. TCDD does not bind to DNA, and indirect tests for DNA damage have been mostly negative. Tumorigenicity by TCDD in rodents has been linked to cellular necrosis, enhanced cell proliferation and tumor promotion. TCDD binds to the Ah receptor, which induces CYP1A1. This binding may be involved in tumorigenicity in rodents; however, additional TCDD-induced toxic changes appear to be required. Biopersistence and organ distribution may play an important role in TCDD dosage extrapolation to humans, but these have not been adequately determined.