Antithyroid effects of coal-derived pollutants.
Endemic goiter in iodide-sufficient areas of the United States and Colombia has been linked to watersheds rich in coal and shale, which several reports suggest are the source of water-borne goitrogens. In this report the potential antithyroid activities of aqueous coal and shale extracts and of compounds identified in aqueous effluents from coal conversion processes were assayed in thyroid peroxidase (TPO) and thyroid slice systems. Aqueous extracts of coal and black shale were potent inhibitors of TPO or 125I organification by thyroid slices. The most abundant water-soluble compounds derived from coal are dihydroxy-phenols, thiocyanate, disulfides, and hydroxypyridines. The dihydroxyphenols resorcinol, 2-methylresorcinol, and 5-methylresorcinol (orcinol) were 26.7, 22.5, and 7.2 times more potent, respectively, than the antithyroid drug 6-propylthiouracil (PTU). Other dihydroxyphenols and thiocyanate were less potent but comparable in activity to PTU. All dihydroxypyridines and 3-hydroxypyridine produced inhibitory effects comparable to PTU. None of the disulfides inhibited TPO. The antiperoxidase effects of combinations of two dihydroxyphenols or one dihydroxyphenol and SCN were additive, whereas the effects of a combination of four dihydroxyphenols at threshold inhibitory concentrations were synergistic, resulting in net effects equivalent to or greater than the sum of the individual effects. Thus, antithyroid effects may be greatly amplified by exposure to multiple coal-derived goitrogens and could be many times that produced by any one of the contributing pollutants. These results demonstrate that potent water-borne goitrogens are derived from coal and shale and that their contamination of water supplies could pose a serious threat of thyroid disorders.
D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D003031:Coal / Q000009:adverse effects* / Q000032:analysis; D004220:Disulfides / Q000633:toxicity; D004347:Drug Interactions; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000633:toxicity; D011725:Pyridines / Q000633:toxicity; D012118:Resorcinols / Q000633:toxicity; D013552:Swine; D013861:Thiocyanates / Q000633:toxicity; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D014873:Water Pollutants / Q000633:toxicity*
D013956:Antithyroid Agents; D003031:Coal; D004220:Disulfides; D010636:Phenols; D011725:Pyridines; D012118:Resorcinols; D013861:Thiocyanates; D014873:Water Pollutants; C014047:hydroxypyridines; D007453:Iodide Peroxidase