Challenges Confronting Risk Analysis of Potential Thyroid Toxicants

Zoeller, R. Thomas

doi:10.1111/1539-6924.00296

Cited by 38 publications

(21 citation statements)

References 254 publications

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“…However, no data are available to support this hypothesis. These life stages are identified as being particularly sensitive to inhibition of thyroid iodine uptake, because they do not have the reserve capacity existing in adult humans (Zoeller, 2003;Scinicariello et al, 2005;Ginsberg et al, 2007).…”

Section: Consideration Of Critical Effects Dose Response Assessment mentioning

confidence: 99%

Risks for public health related to the presence of chlorate in food

Publication¹

2015

EFS2

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Following a request from the European Commission, the risks to human health related to the presence of chlorate in food were assessed by the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel). The presence of chlorate in food can arise from the use of chlorinated water for food processing and the disinfection of foodprocessing equipment. Inhibition of iodine uptake in humans was identified as the critical effect for chronic exposure to chlorate. A tolerable daily intake (TDI) of 3 µg chlorate/kg body weight (b.w.) was set by readacross from a TDI of 0.3 µg/kg b.w. derived for this effect for perchlorate, multiplied by a factor of 10 to account for the lower potency of chlorate. Formation of methaemoglobin was identified as the critical acute effect of chlorate. An acute reference dose (ARfD) of 36 µg chlorate/kg b.w. was derived from a no-observedeffect-level for chlorate in a controlled clinical study. Chronic exposure of adolescent and adult age classes did not exceed the TDI. However, at the 95th percentile the TDI was exceeded in all surveys in 'Infants' and 'Toddlers' and in some surveys in 'Other children'. Chronic exposures are of concern in particular in younger age groups with mild or moderate iodine deficiency. Mean and 95th percentile acute exposures were below the ARfD for all age groups indicating no concern. Based on the current practices in food industry, application of a hypothetical maximum residue limit (MRL) of 0.7 mg/kg for all foodstuffs and drinking water would only minimally reduce acute/chronic exposures and related risks. Assuming chlorate concentrations of 0.7 mg/kg for all foods and drinking water consumed in a day, acute exposures would increase by up to about 5-fold and the ARfD be exceeded at mean estimates in 'Infants' and 'Toddlers' and at 95th percentile also in 'Other children'and 'Adults'. Chlorate is formed as a by-product when using chlorine, chlorine dioxide or hypochlorite for the disinfection of drinking water, water for food production and surfaces coming into contact with food. Chlorination of animal-derived food is not allowed in the EU, while washing of plant-derived food with chlorine disinfected water can be permitted under national regulations. No maximum levels for chlorate in drinking water have been set in the European Union (EU) while the World Health Organisation (WHO) has established a guideline level for chlorate in drinking water of 0.7 mg/L. © EuropeanIn many fruit and vegetable commodities chlorate levels exceeding the default MRL of 0.01 mg/kg are found.Based on the available information, the CONTAM Panel assumes that chlorate residues in food result mainly from the use of chlorinated water for food processing (e.g. washing) and from the disinfection of surfaces and food processing equipment coming into contact with food.The EFSA Evidence Management Unit (DATA Unit) launched a call for data on chlorate levels in food and drinking water. After a quality assessment of the analytical data and their evaluation, 8 028 samples remained for anal...

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Section: Consideration Of Critical Effects Dose Response Assessment mentioning

confidence: 99%

Risks for public health related to the presence of chlorate in food

Publication¹

2015

EFS2

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“…Exogenous chemicals that can interfere with the thyroid hormone axis could pose a significant hazard to human and wildlife health (Colborn 2002; Zoeller 2003). Amphibians represent a suitable model for monitoring reproductive performance, advanced development including metamorphosis, and sexual maturation (Kloas 2002).…”

Section: Amphibiansmentioning

confidence: 99%

Application of Ecotoxicogenomics for Studying Endocrine Disruption in Vertebrates and Invertebrates

Iguchi

Watanabe

Katsu

2006

Environ Health Perspect

104

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Chemicals released into the environment potentially disrupt the endocrine system in wild animals and humans. Developing organisms are particularly sensitive to estrogenic chemicals. Exposure to estrogens or estrogenic chemicals during critical periods of development induces persistent changes in both reproductive and nonreproductive organs, including persistent molecular alterations. Estrogen-responsive genes and critical developmental windows of various animal species, therefore, need to be identified for investigators to understand the molecular basis of estrogenic activity during embryonic development. For investigators to understand molecular mechanisms of toxicity in various species, toxicogenomics/ecotoxicogenomics, defined as the integration of genomics (transcriptomics, proteomics, metabolomics) into toxicology and ecotoxicology, need to be established as powerful tools for research. As the initial step toward using genomics to examine endocrine-disrupting chemicals, estrogen receptors and other steroid hormone receptors have been cloned in various species, including reptiles, amphibians, and fish, and alterations in the expression of these genes in response to chemicals were investigated. We are identifying estrogen-responsive genes in mouse reproductive tracts using cDNA microarrays and trying to establish microarray systems in the American alligator, roach, medaka, and water fleas (Daphnia magna). It is too early to define common estrogen-responsive genes in various animal species; however, toxicogenomics and ectotoxicogenomics provide powerful tools to help us understand the molecular mechanism of chemical toxicities in various animal species.

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“…Both TRH and TSH secretion are negatively regulated by THs: when T 4 reaches an adequate circulating level, the hypothalamus and pituitary reduce their output of TRH and TSH; they increase their output of TRH and TSH when the circulating blood level of T 4 is low. A number of thyroid genes, including NIS , thyroglobulin ( Tg ), and thyroid peroxidase ( TPO ), are stimulated by TSH and promote the synthesis of TH (Zoeller 2003). …”

Section: Thyroid Hormone Synthesismentioning

confidence: 99%

“…The authors suggested that this failure of perchlorate to influence circulating levels of TH resulted from the storage capacity of the normal adult thyroid gland, which contains unreleased stored hormones lasting for several months. However, as pointed out by Zoeller (2003), the case may be different for a late gestation fetus or neonate, where the estimated intrathyroidal amount of hormone stored is less than that required for 1 day (Van den Hove et al 1999; Vulsma et al 1989). Thus, the concentration of perchlorate sufficient to reduce thyroidal iodine uptake in a fetus or neonate may be sufficient to produce a significant decrement in circulating levels of TH.…”

Section: Relevant Studies Of Perchlorate In Humansmentioning

confidence: 99%

Genetic Factors That Might Lead to Different Responses in Individuals Exposed to Perchlorate

Scinicariello

Murray

Smith

et al. 2005

Environ Health Perspect

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Perchlorate has been detected in groundwater in many parts of the United States, and recent detection in vegetable and dairy food products indicates that contamination by perchlorate is more widespread than previously thought. Perchlorate is a competitive inhibitor of the sodium iodide symporter, the thyroid cell–surface protein responsible for transporting iodide from the plasma into the thyroid. An estimated 4.3% of the U.S. population is subclinically hypothyroid, and 6.9% of pregnant women may have low iodine intake. Congenital hypothyroidism affects 1 in 3,000 to 1 in 4,000 infants, and 15% of these cases have been attributed to genetic defects. Our objective in this review is to identify genetic biomarkers that would help define subpopulations sensitive to environmental perchlorate exposure. We review the literature to identify genetic defects involved in the iodination process of the thyroid hormone synthesis, particularly defects in iodide transport from circulation into the thyroid cell, defects in iodide transport from the thyroid cell to the follicular lumen (Pendred syndrome), and defects of iodide organification. Furthermore, we summarize relevant studies of perchlorate in humans. Because of perchlorate inhibition of iodide uptake, it is biologically plausible that chronic ingestion of perchlorate through contaminated sources may cause some degree of iodine discharge in populations that are genetically susceptible to defects in the iodination process of the thyroid hormone synthesis, thus deteriorating their conditions. We conclude that future studies linking human disease and environmental perchlorate exposure should consider the genetic makeup of the participants, actual perchlorate exposure levels, and individual iodine intake/excretion levels.

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Challenges Confronting Risk Analysis of Potential Thyroid Toxicants

Cited by 38 publications

References 254 publications

Risks for public health related to the presence of chlorate in food

Risks for public health related to the presence of chlorate in food

Application of Ecotoxicogenomics for Studying Endocrine Disruption in Vertebrates and Invertebrates

Genetic Factors That Might Lead to Different Responses in Individuals Exposed to Perchlorate

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