Health Implications of Perchlorate Ingestion (2005) / Chapter Skim
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5 Risk Characterization of Perchlorate
5 Risk Characterization of Perchlorate
Pages 164-181
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From page 164... ...
EPA's model predicts that the changes in thyroid hormone production and increasesinTSHproductioncouldleadtoaltereddevelopmentandultimately birth defects in children and to thyroid hyperplasia and ultimately thyroid tumors in adults.
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From page 165... ...
Humans are much less susceptible than rats to disruption of thyroid function and therefore are not likely to develop thyroid tumors as a result of perchlorate exposure. The committee concludes that the most reasonable pathway of events after changes in thyroid hormone and TSH secretion would be thyroid hypertrophy or hyperplasia, possibly leading to hypothyroidism.
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From page 166... ...
. The committee, however, does not view transient changes in serum thyroid hormone and TSH concentrations as adverse health effects; it considers them to be biochemical changes that could precede adverse effects.
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From page 167... ...
POINT OF DEPARTURE A primary purpose of EPA's perchlorate risk assessment was to calculate an oral RfD.
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From page 168... ...
Theindividual uncertainty factors used to derive an RfD are discussed in the following sections. For the perchlorate risk assessment, EPA based its point of departure on reported changes in brain morphometry, thyroid histopathology, and serum thyroid hormone concentrations after oral administration of perchlorate to rats.
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From page 169... ...
Although the data from epidemiologic studies of the general population provide some information on possible effects of perchlorate exposure, those studies are ecologic and inherently limited with respect to establishing causality and serving as a basis of quantitative risk assessment. Furthermore, those studies typically focused on changes in serum thyroid hormone and TSH concentrations or clinical manifestations of the changes, not on inhibition of iodide uptake by the thyroid.
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From page 170... ...
Serum TSH concentrations decreased slightly andtransiently inthehighest-dosegroup -- achange in the direction opposite what would be expected had thyroid hormone secretion decreased. The study identified a NOEL for inhibition of iodide uptake by the thyroid at 0.007 mg/kg per day, which is consistent with findings of similar studies in humans (Lawrence et al.
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From page 171... ...
1992; see Chapter 2) and extensive human and animal data that demonstrate that there will be no progression to adverse effects if no inhibition of iodide uptake occurs (see Figure 5-2)
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From page 172... ...
In its draft risk assessment, EPA proposed a composite uncertainty factor of 300 to apply to its point of departure of 0.01 mg/kg per day, which was based on changes reported in brain morphometry, thyroid histopathology, and serum thyroid hormone concentrations in rats given perchlorate orally. Factors for intraspecies variability, use of a LOAEL, lack of chronic data, and other database gaps contributed to EPA's composite factor.
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From page 173... ...
. However, serum thyroid hormone and TSH concentrations of those who had a daily iodide intake less than 50 :g were similar to those of people who had a higher daily iodide intake (Hollowell et al.
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From page 174... ...
That recommendation is considered to be a more conservative and health-protective approach for the perchlorate riskassessmentthantraditionalriskassessments that use a point of departure based on an adverse effect. In its 2002 draft risk assessment (EPA 2002a)
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From page 175... ...
If some inhibition of iodide uptake by the thyroid did occur at the minimal dose proposed for the point of departure, data from humans indicate that longer exposures are not likely to result in a greater or more severe response. According to preliminary data presented in an abstract, administration of perchlorate to normal subjects for 6 months at 0.007 and 0.04 mg/kg per day had no effect on thyroid function (Braverman et al.
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From page 176... ...
Toxicology studies designed to identify the most sensitive effect of perchlorate exposure have indicated that the thyroid is the primary target of perchlorate exposure in rats, which is the most sensitive species studied (see Chapter 4)
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The committee also differs with EPA regarding the definition of adverse effects associated with perchlorate exposure. The committee does not think that transient changes in serum thyroid hormone or TSH concentrations are necessarily adverse effects.
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From page 178... ...
2004. A rat neurodevelopmental evaluation of offspring, including evaluation of adult and neonatal thyroid, frommothers treated with ammonium perchlorate in drinking water.
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From page 179... ...
2000. A Neurodevelopmental Study of Oral Ammonium Perchlorate Exposure on the Motor Activity of Pre-Weanling Rat Pups.
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From page 180... ...
January 24, 2003. (Presentation at the Fifth Meeting on Assess the Health Implications of Perchlorate Ingestion, July 29 30, 2004, Washington, DC.)
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From page 181... ...
1998. A 90-Day Drinking Water Toxicity Study in Rats with Ammonium Perchlorate: Amended Final Report.
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