Primary Congenital Hypothyroidism, Newborn Thyroid Function, and Environmental Perchlorate Exposure Among Residents of a Southern California Community

Kelsh, Michael A.; Buffler, Patricia A.; Daaboul, Jorge J.; Rutherford, George W.; Lau, Edmund; Barnard, Julie C.; Exuzides, Alex; Madl, Amy K.; Palmer, Lynn G.; Lorey, Fred

doi:10.1097/01.jom.0000091683.25325.55

Cited by 36 publications

(37 citation statements)

References 19 publications

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“…This observation is in line with other cohort studies [30][31]. For example, Lawrence et al [30] demonstrated the sensitivity of the thyroid iodide trap to perchlorate in nine healthy men who were daily administered a dose of 10 mg perchlorate daily for 2 weeks, but also found that circulating concentrations of TH and TSH were not affected.…”

Section: Perchloratessupporting

confidence: 86%

Endocrine disruptors and thyroid hormone physiology

Jugan

Lévi

Blondeau

2010

Biochemical Pharmacology

215

115

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Endocrine disruptors are man-made chemicals that can disrupt the synthesis, circulating levels, and peripheral action of hormones. The disruption of sex hormones was subject of intensive research, but thyroid hormone synthesis and signaling are now also recognized as important targets of endocrine disruptors. The neurological development of mammals is largely dependent on normal thyroid hormone homeostasis, and it is likely to be particularly sensitive to disruption of the thyroid axis. Here, we survey the main thyroid-disrupting chemicals, such as polychlorinated biphenyls, perchlorates, and brominated flame retardants, that are characteristic disruptors of thyroid hormone homeostasis, and look at their suspected relationships to impaired development of the human central nervous system. The review then focuses on disrupting mechanisms known to be directly or indirectly related to the transcriptional activity of the thyroid hormone receptors.

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Section: Perchloratessupporting

confidence: 86%

Endocrine disruptors and thyroid hormone physiology

Jugan

Lévi

Blondeau

2010

Biochemical Pharmacology

215

115

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“…Perchlorate levels in Las Vegas ranged between 9 and 15 lg/L during the study period while perchlorate levels in Reno were below the detection limit of 4 lg/L. Kelsh et al (2003), investigating a perchlorate exposed population in California, also found no increase in the odds ratio for either increased serum TSH or diagnosis of primary congenital hypothyroidism. Finally, Lamm and Doemland (1999) reported no elevation in the incidence of congenital hypothyroidism in seven California and Nevada counties where perchlorate was detected in drinking water wells.…”

Section: Discussionmentioning

confidence: 86%

“…Animal studies of these endpoints (e.g., alterations in the size of various brain structures, altered patterns of myelination, behavioral responses) have not been definitive with negative results in rabbits (York et al, 2001a,b) and contradictory findings in rats (Argus, 2001;York et al, 2001a,b). Ecological studies conducted in human populations (focusing on neonatal hormone levels rather than neurodevelopmental endpoints) have yielded generally negative findings (Crump et al, 2000;Kelsh et al, 2003;Lamm and Doemland, 1999;Li et al, 2000a,b) with one positive published study (Brechner et al, 2000). The animal and human data have been subject to considerable scrutiny and are currently the subject of vigorous debate.…”

Section: Disruption Of Thyroid Hormone Homeostasismentioning

confidence: 99%

Interspecies differences in susceptibility to perturbation of thyroid homeostasis: a case study with perchlorate

Lewandowski

Seeley

Beck

2004

Regulatory Toxicology and Pharmacology

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“…Results are shown in Figure 1 of the current paper. 12) Kelsh et al [37]. This was an epidemiological study of the relationship between exposure to perchlorate in water and the incidence of primary congenital hypothyroidism in a population of 15,090 newborns in California.…”

Section: Epidemiological and Clinical Studies Databasementioning

confidence: 99%

Implications of the Reanalysis and Weight of Evidence Determination of Human Health Studies for Exposure to Perchlorates under Cumulative and Aggregate Risk Assessment

Crawford‐Brown¹,

Crawford-Brown²

2016

JEP

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This paper applies cumulative and aggregate risk methods and weight of evidence determination to re-analysis of epidemiological and clinical studies of exposure to perchlorates. The implications of cumulative and aggregate risk are considered for 28 epidemiological studies on IUI, serum thyroid hormone levels and clinical indicators. Consideration is given to simultaneous exposures to perchlorates, nitrates, thiocyanates and organohalogens in the study populations. The elevation of effects by perchlorates alone is found only in the studies that use urinary perchlorate as the metric of exposure. These studies are beset by a problem with use of urinary perchlorate concentration in that there is large inter-subject variability in the relationship between intake and urinary concentration due to differences in metabolism and disposition of the compounds following ingestion. As a result, an individual placed into the "high urinary concentration" group may be there due to high values of exposure, to long biological clearance half-lives, or due to high transfer fractions from the serum into the urine. The influence could be removed by correcting urinary levels by measured clearance half-times for individuals in a study, but that has not been done in the case of the studies examined here. It is of interest therefore that the studies that use direct measures of intake of perchlorates rather than urine concentration fail to display the hormone effects. The current study uses a "weight of evidence" approach for perchlorates, employing all 28 studies. The result is a slope of the exposureresponse curve (percentage change in hormone effect per unit exposure) of 0.3% per µg/kg-day, with 95% confidence interval of (−0.05%, 1%). This confidence interval for the slope encompasses 0, indicating no statistically significant slope when all data are combined in a weight of evidence determination. This is consistent with the conclusions of the USEPA and EFSA that the epidemiological studies do not provide compelling evidence for a causal association between exposures to perchlorates and either hormone effects or clinically adverse effects. The conclusions are 1) that current epidemiological results do not provide evidence of effects induced by perchlorates apart from the IUI effects, 2) that the same results provide evidence that the IUI effects induced at environmental levels of exposure are associated with down-stream adverse effects and 3) that effective risk management requires the cumulative and aggregate risk framework adopted here, suggesting a need for risk assessors to return to the original studies and provide separate estimates of exposure-response relationships for all four compounds or at the least to control for exposures to nitrates, thiocyanates and organohalogens.

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Primary Congenital Hypothyroidism, Newborn Thyroid Function, and Environmental Perchlorate Exposure Among Residents of a Southern California Community

Cited by 36 publications

References 19 publications

Endocrine disruptors and thyroid hormone physiology

Endocrine disruptors and thyroid hormone physiology

Interspecies differences in susceptibility to perturbation of thyroid homeostasis: a case study with perchlorate

Implications of the Reanalysis and Weight of Evidence Determination of Human Health Studies for Exposure to Perchlorates under Cumulative and Aggregate Risk Assessment

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