Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.
Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.
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DOI：
10.1289/ehp.02110927
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发表时间：
2002-09
影响因子：
10.4
通讯作者：
Greer SE
中科院分区：
文献类型：
--
作者：
Greer MA;Goodman G;Pleus RC;Greer SE
一种灵敏的新检测方法的应用揭示了美国西南部地下水中普遍存在的高氯酸盐污染，通常为0.005-0.020 mg/L（5-20 ppb）。高氯酸盐是碘离子从血液主动转运到甲状腺的过程的竞争性抑制剂。高氯酸盐的这种抑制作用是其药物用途（治疗甲状腺功能亢进症）及其潜在毒性的基础。为了确定高氯酸盐抑制甲状腺碘摄取的剂量反应以及对甲状腺激素的任何短期影响，我们给37名男性和女性志愿者饮用水中的高氯酸盐0.007、0.02、0.1或0.5 mg/kg-天，持续14天。在24名受试者中，我们在暴露前、暴露第2天（E2）和第14天（E14）以及暴露后15天（P15）进行了8小时和24小时甲状腺（123）I摄取（RAIU）测量。在另外13名受试者中，我们省略了E2研究和8小时P15研究。我们观察到所有剂量组和测量日的8小时和24小时RAIU之间存在强相关性。我们发现E2和E14在抑制给定高氯酸盐剂量产生的RAIU方面没有差异。我们也没有发现性别差异。在E2和E14时，剂量反应均为剂量对数的负线性函数。基于所有受试者中8小时和24小时RAIU对E14抑制的剂量反应，我们得出了真实无作用水平的估计值：分别为5.2和6.4微克/千克-天。鉴于默认的体重和暴露假设，如果饮用水供应中含有的高氯酸盐浓度分别约为180和220微克/升（ppb），则成年人将摄入这些剂量。P15时，RAIU与基线无显著差异。在24名受试者中，我们测量了血清甲状腺素（总的和游离的），三碘甲状腺原氨酸，和促甲状腺激素的血液采样16次在整个研究。只有0.5 mg/kg-天剂量组显示对血清激素有任何影响：在高氯酸盐暴露期间，早晨抽血时促甲状腺激素水平呈轻微下降趋势，到P15时恢复。
Application of a sensitive new detection method has revealed widespread perchlorate contamination of groundwater in the southwestern United States, typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor of the process by which iodide is actively transported from the bloodstream into the thyroid. This inhibitory action of perchlorate is the basis of its pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential toxicity. To establish the dose response in humans for perchlorate inhibition of thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days 2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation between the 8- and 24-hr RAIU over all dose groups and measurement days. We found no difference between E2 and E14 in the inhibition of RAIU produced by a given perchlorate dose. We also found no sex difference. On both E2 and E14, the dose response was a negative linear function of the logarithm of dose. Based on the dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day, respectively. Given default body weight and exposure assumptions, these doses would be ingested by an adult if the drinking-water supply contained perchlorate at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On P15, RAIU was not significantly different from baseline. In 24 subjects we measured serum levels of thyroxine (total and free), triiodothyronine, and thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg-day dose group showed any effect on serum hormones: a slight downward trend in thyrotropin levels in morning blood draws during perchlorate exposure, with recovery by P15.
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影响因子：
6.6
作者：
Buchinger, W;LorenzWawschinek, O;Eber, O
通讯作者：
Eber, O
影响因子：
5.8
作者：
Hollowell, JG;Staehling, NW;Jackson, RJ
通讯作者：
Jackson, RJ
影响因子：
15.9
作者：
GREER, MA
通讯作者：
GREER, MA
DOI：
10.1097/00043764-199904000-00006
发表时间：
1999-04-01
影响因子：
3.2
作者：
Lamm, SH;Braverman, LE;Howearth, G
通讯作者：
Howearth, G
影响因子：
2.6
作者：
Fisher, J;Todd, P;Yu, K
通讯作者：
Yu, K