| Mode of Carcinogenic Action of Pesticides Inducing Thyroid Follicular Cell Tumors in Rodents Pamela M. Hurley, Richard N. Hill, and Rick J. Whiting Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, DC 20460 USA Abstract
Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly acetochlor ; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N -octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors ; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only ; no chemical is mutagenic only ; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action. Key words : induction of hepatic microsomal enzymes, iodide pump, mode of carcinogenic action, 5´-monodeiodinase activity, pesticides, thyroid follicular cell tumors, thyroid hormone, thyroid peroxidase activity, thyroid-stimulating hormone. Environ Health Perspect 106:437-445 (1998) . [Online 26 June 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p437-445hurley/ abstract.html Address correspondence to P.M. Hurley, Office of Pesticide Programs (7509C) , U.S. Environmental Protection Agency, 401 M Street, S.W., Washington, DC 20460 USA. The authors would like to acknowledge the help of Esther Rinde in determining the number of pesticide peer reviews and John Abbotts for drawing the chemical structures. Received 29 September 1997 ; accepted 16 April 1998.
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