Health Implications of Perchlorate Ingestion (2005) / Chapter Skim
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3 Epidemiologic Studies of Occupational and Environmental Exposures to Perchlorate
3 Epidemiologic Studies of Occupational and Environmental Exposures to Perchlorate
Pages 75-114
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From page 75... ...
2004) ; and the remainder are primarily ecologic investigations that compared measures of thyroid function or disease and neurodevelopmental outcomesinneonates,children,andadultsingeographicallydefinedgroups with and without detectable perchlorate in community water supplies (Lamm and Doemland 1999; Brechner et al.
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From page 76... ...
That design is subject to what is referred to as the ecologic fallacy: associations observed at the ecologic level may not apply at the individual level. For example, an observation that the average serum TSH concentration is higher in newborns in a city in which the water supply contains perchlorate than in newborns in cities in which the drinking water does not contain perchlorate would be compatible with a perchlorate effect on thyroid function.
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From page 77... ...
Another limitationofecologicstudiesisthattheirdesign cannot control for many confounding factors, because such data are not usually available at the population level. Results of ecologic studies can be useful in providing supporting data on a possible causal relation, but they cannot themselves provide direct evidence of causation.
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From page 78... ...
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From page 79... ...
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From page 80... ...
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From page 81... ...
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From page 82... ...
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From page 83... ...
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From page 84... ...
84 147 HST TSH, and mu ser CI, illiunitsm SMR, ratio; ntsem idismor high of ved pothy /L,Um Com hy cases obser California; incidence trichloroethylene; CA, illiliter;m TCE, ndex;i per ssa standardized Findings ajor M body-m crounitsim,L SIR, thyroxine;, 4 T BMI, U/m:; billion; per se parts Arizona; utcomO kilogram triiodothyronine;, 3 per nte AZ,; ppb, T s ratio; Adjustm Factor disorder crogramim expected; over prevalence e reports. g/kg,:; observed xposurE study final and illigramm,gm; O/E, standardized year.
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From page 85... ...
In another study of occupational exposure among 254 employees at an ammonium perchlorate production facility in Nevada, those who agreed to participate in the study were investigated for possible acute or chronic effects of perchlorate exposure on thyroid function (Gibbs et al.
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From page 86... ...
In the analysis of cumulative lifetime exposure to ammonium perchlorate, neither the dose estimate nor the categorical exposure variable was significantly related to measures of thyroid hormone and TSH production. They were unrelated to all but one (white blood cell count)
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From page 87... ...
. Thyroid status was assessed by measuring serum TSH, T4, T3, free T4 index, thyroid hormone binding ratio, and thyroid peroxidase antibodies and by conducting clinical examinations.
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From page 88... ...
Preliminary analyses of data from another study of workers in the Utah ammonium perchlorate production facility were presented at a public meeting of the committee in May 2004 and later in a draft manuscript (Braverman et al.
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From page 89... ...
The thyroid diseases studied were simple and nonspecified goiter, nontoxic nodular goiter, thyrotoxicosis with or without goiter, congenital hypothyroidism, acquired hypothyroidism, thyroiditis, other disorders of the thyroid, and malignant neoplasms of the thyroid (ICD-9 Codes 193 and 240246)
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From page 90... ...
compared the observed and expected numbers of incident cancer cases among residents of 13 contiguous census tracts in Redlands, California, in San Bernardino County. That area is served by the Desert Sierra Cancer Surveillance Program, a regional cancer registry that includes four counties in Southern California, one of which is San Bernardino County.
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From page 91... ...
STUDIES IN NEONATES, CHILDREN, AND PREGNANT WOMEN Ecologic Studies Based on Newborn Screening Data Congenital Hypothyroidism A primary concern regarding exposure to perchlorate in drinking water is its potential effect on the developing fetus and the possibility of inducing or contributing to hypothyroidism in the newborn period. One of the first ecologic studies of perchlorate exposure and thyroid disease in newborns was done by Lamm and Doemland in 1999.
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From page 92... ...
Thyroid Hormone and TSH Production A series of ecologic studies examined differences in thyroid hormone and TSH production in newborns in Las Vegas (mean monthly concentrations of perchlorate in drinking water, undetectable to 15 ppb [15 :g/L]
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From page 93... ...
At the time of those studies, Nevada used a two-stage screening procedure for thyroid function in which newborns who had T4 concentrations below the 10th percentile had a follow-up TSH blood test. Data on TSH concentrations, excluding those obtained in the first day of life, were compared in newborns in Las Vegas (n = 407)
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From page 94... ...
(2000) ecologic study, perchlorate exposures in infants' mothers were not directly measured; in fact, drinking-water concentrations of perchlorate were not derived from the same period as the newborn screening results.
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From page 95... ...
examined the relation of perchlorate exposure to prevalence of abnormal newborn blood screening concentrations of T4 and TSH and to presumptive and confirmed casesofcongenitalhypothyroidism. Thestudyincluded507,982California infants born in 1996 for whom newborn screening results were available.
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From page 96... ...
Compared with infants living in ZIP codes that had no measurable perchlorate in the water, the odds of presumptive congenital hypothyroidism by category of exposure were 1.15 (95% CI, 1.12-1.17)
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From page 97... ...
(2003) examined the frequency of congenital hypothyroidism and of high blood TSH concentrations among newborns in 1983-1997 whose mothers resided in one of two California communities and who were screened as part of the California Newborn Screening Program.
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From page 98... ...
During the study period, the California Newborn Screening Program measured TSH only among infants who first screened in the lower 5% of T4 concentrations. Thus, TSH concentrations are available only for infants who also had low T4 concentrations.
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From page 99... ...
(2000) compared thyroid hormone and TSH production andthefrequency ofthyroiddiseaseinnewbornsandinschool-agechildren in three Chilean cities with different perchlorate concentrations in their municipal water supplies.
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From page 100... ...
. Serum free T4 levels were significantly higher in children in Chanaral and Taltal than Antofagasta after adjustment for age, sex, and urinary iodide levels; the difference was opposite the direction predicted on the basis of competitive perchlorate inhibition of iodide uptake.
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From page 101... ...
, newborns in Taltal had statistically significantly lower log serum TSH concentrations; mean log TSH levels did not vary significantly between newborns in the other two cities (Crump et al.
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From page 102... ...
Ethnicity has been shown in some studies to be related to risk of congenital hypothyroidism or to thyroid hormone concentrations, at least in newborns (Lamm and Doemland 1999; Brechner et al. 2000; Schwartz 2001; Kelsh et al.
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From page 103... ...
experience. The mean urinary iodide excretion in children in the three Chilean cities (61-77 :g/dL)
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From page 104... ...
On the basis of the calculations, the committee concludes that iodide intake in the population in question does not interfere with the study's ability to detect effects of perchlorate exposure at up to 120 ppb (120 :g/L) on iodide uptake, if effects are present.
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From page 105... ...
Thyroid Hormone and TSH Production in Pregnant Women and Their Newborns A second study among pregnant women and their newborns in each of the three cities in Chile examined the relation between perchlorate exposure during pregnancy, indexes of maternal thyroid function, and thyroid hormone concentrations in the newborns (Gibbs 2003b)
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From page 106... ...
The study had not been published at the time of the committee's deliberations; therefore, it did not use the results in formulating its conclusions. Ecologic Studies of Neurodevelopment in Children There are sparse data concerning the relation between perchlorate exposure and neurodevelopmental disorders in children.
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From page 107... ...
) as measured in 1997-2001; Washoe County, which includes Reno and has no detectable perchlorate in the public water supply; and the remainder of Nevada, was considered a "rural" control for Las Vegas.
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From page 108... ...
and abnormalities of thyroid hormone and TSH production in newborns, as well as thyroid diseases (such as congenital hypothyroidism and goiter) and cancer in children and adults (Lamm and Doemland 1999; Brechner et al.
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From page 109... ...
Committee Conclusions Drawn from Epidemiologic Data on Specific Health Outcomes Congenital Hypothyroidism Ecologic data alone are not sufficient to demonstrate whether or not an association is causal, but they do provide evidence that can be used to evaluate possible associations. Acknowledging that ecologic data alone are inherently limited in drawing causal inferences, the committee concludes that the available epidemiologic evidence is not consistent with a causal association between perchlorate exposure and congenital hypothyroidism as defined by the authors of the studies reviewed here.
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From page 110... ...
The thyroid diseases and thyroid measures investigated included simple and nonspecified goiter, nontoxic nodular goiter, thyrotoxicosis with or without goiter, acquired hypothyroidism, thyroiditis, and other disorders of the thyroid, and measures of serum TSH and the two thyroid hormones. In occupational studies, perchlorate exposures as high as 0.5 mg/kg per day have not been associated with adverse effects on thyroid function in workers, but small samples in some studies may have reduced the ability to identify important differences, and studies were limited to workers who remained in the workforce.
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From page 111... ...
2004. Epidemiologic Studies of Primary Congenital Hypothyroidism and Newborn Thyroid Function Among California Residents, Final Report.
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From page 112... ...
2003. Primary congenital hypothyroidism, newborn thyroid function, and environmental perchlorate exposure among residents of a southern California community.
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From page 113... ...
2002. Congenital hypothyroidism: An analysis of persisting deficits and associated factors.
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From page 114... ...
2003. Long-term follow-up of children born with sporadic congenital hypothyroidism.
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