Lindsay R H, Hill J B, Gaitan E, Cooksey R C, Jolley R L
Veterans Affairs Medical Center, Birmingham, Alabama.
J Toxicol Environ Health. 1992 Dec;37(4):467-81. doi: 10.1080/15287399209531686.
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.
美国和哥伦比亚碘充足地区的地方性甲状腺肿与富含煤和页岩的流域有关，几份报告表明这些流域是水中致甲状腺肿物质的来源。在本报告中，在甲状腺过氧化物酶（TPO）和甲状腺切片系统中检测了煤和页岩水提取物以及煤转化过程废水里鉴定出的化合物的潜在抗甲状腺活性。煤和黑色页岩的水提取物是TPO或甲状腺切片进行125I有机化的强效抑制剂。煤中最丰富的水溶性化合物是二羟基酚、硫氰酸盐、二硫化物和羟基吡啶。二羟基酚间苯二酚、2 - 甲基间苯二酚和5 - 甲基间苯二酚（苔黑酚）的效力分别比抗甲状腺药物6 - 丙基硫氧嘧啶（PTU）高26.7倍、22.5倍和7.2倍。其他二羟基酚和硫氰酸盐效力较低，但活性与PTU相当。所有羟基吡啶和3 - 羟基吡啶产生的抑制作用与PTU相当。所有二硫化物均未抑制TPO。两种二羟基酚或一种二羟基酚与硫氰酸盐组合的抗过氧化物酶作用是相加的，而四种二羟基酚在阈抑制浓度下组合的作用是协同的，产生的净效应等于或大于各单独效应之和。因此，接触多种煤衍生的致甲状腺肿物质可能会极大地放大抗甲状腺作用，其作用可能是任何一种相关污染物产生作用的许多倍。这些结果表明，强效的水中致甲状腺肿物质源自煤和页岩，它们对供水的污染可能对甲状腺疾病构成严重威胁。
