An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Volume 2.

Abstract : Despite conclusive evidence that chiorophenols are potent carcinogens in laboratory animals, the carcinogenicity of dioxin in humans remains controversial. Traditional difficulties in extrapolating animal data to humans have limited the applicability and relevance of much of the experimental work. Numerous long-term exposure studies have established the carcinogenicity of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) in rats (1,2), mice (3-5), and hamsters (6). The consensus of most research is that TCDD is only weakly mutagenic and does not covalenfly bind to DNA or cause it to initiate repair synthesis, but that it does behave as a strong tumor promoter at the cellular level (7). The oncogemc response to TCDD in animals has been shown repeatedly to depend upon the age, sex, and strain of species as well as the dose and route of administration (8-10). In varying doses and routes of administration, TCDD has produced malignant neoplasms at multiple sites in rats (lung, oropharyngeal, thyroid, adrenal, and liver) (2,3), in mice (thyroid, thymus, connective tissue, and liver) (3), and in hamsters (cutaneous) (6). As summarized in detail in a recent review article (11), much of the basic research into the carcinogenicity of TCDD in laboratory animals has focused on the aryl hydrocarbon (Ah) receptor and the induction of the cytochrome PASO enyyme system (12-16). Though the Ah receptor has been isolated from the tissue of several human organs (e.g., liver, colon, tonsils) (17-22), the relevance of these observations to dioxin toxicity remains to be proven (23).