#57 Perchlorate dosage on thyroid – laboratory confirmation of occupational epidemiology findings

PURPOSE: Perchlorate is known to affect the thyroid by blocking the uptake of iodine at the sodium-iodide symporter (NIS) receptor site of the basolateral membrane of the thyroidal cell in a dose-response manner. A previous occupational study of employees at a plant where perchlorate was manufactured examined for the level at which iodine uptake inhibition in chronically-exposed workers was sufficient to cause a reduction in the free thyroxine index (FTI). The data analysis predicted a 10% inhibition at an exposure of about 45 mg/day and demonstrated no effect on FTI at occupational exposures of about 35, 11, 4, and 1 mg/day.METHODS: The occupational exposures were a mixture of inhalation, ingestion, and possibly dermal routes. The dosages had been modeled based on urine perchlorate levels across one work shift with airborne exposures measured. The laboratory studies were conducted using measured oral dosages in drinking water for a two-week period with determination of radio-active iodine uptake before, during, and following exposure period. Thyroid function tests and urine and serum concentrations of perchlorate and iodine were also determined.RESULTS: Laboratory studies demonstrated a significant 38% inhibition of iodine uptake at 10 mg/day and a non-significant 10% inhibition at 3 mg/day (Lawrence 2000, 2000b). Another laboratory conducted studies at doses of about 35, 7, 1.4, and 0.5 mg/day and found iodine inhibition rates of 67%, 45%, 16%, and 2% (not significant) (Greer et al., 2002). Neither free thyroxine index nor free thyroxine levels were affected at any laboratory exposure level. Log-linear extrapolation of the data indicated that an exposure level slightly below 0.5 mg/day perchlorate would be below the threshold level for iodine uptake inhibition in these populations.CONCLUSION: An occupational health study found no adverse effect on thyroid hormone (FTI) at exposures of about 1, 4, 11, and 35 mg/day perchlorate, a chemical known to inhibit iodine uptake. Measurement of iodine uptake inhibition at similar levels showed that the uptake inhibition threshold was just below 0.5 mg/day and that adverse effects on thyroid hormone (FTI) were not seen with exposures equivalent to 67% inhibition. Thus, a range of iodine uptake inhibition at which thyroxine level appears not to be adversely affected is indicated.     

Ammonium perchlorate effects on thyroid function and growth in bobwhite quail chicks

Bobwhite quail chicks were used to investigate ammonium perchlorate (AP; NH4ClO4) effects on thyroid function and growth. Beginning at 3 to 4 d posthatch, we evaluated organismal thyroid status (circulating hormones), activation of the hypothalamic-pituitary-thyroid axis (thyroid wt) and thyroidal hormone content over a wide range of AP concentrations (50 microg/L - 4,000 mg/L) in drinking water, for relatively short (2-week) and longer (8-week) exposures. Thyroidal thyroxine (T4) content, the most sensitive index of decreased thyroid function, decreased markedly in response to increasing perchlorate exposure. Thyroid weight and plasma T4 were less sensitive indicators and similar in their ability to detect thyroid changes. Growth measurements (body wt and skeletal growth) were very insensitive indices. Because thyroids contain large hormone stores, with low exposures or short time periods, these stores can be used to maintain circulating hormones, at least temporarily. Most depletion of thyroidal T4 occurred during the first two weeks of AP exposure. Subsequent decreases were at a slower rate presumably because thyrotropin stimulation of the thyroids at least partially compensated for some of the perchlorate effect. Additional studies of the interactions between AP concentration and exposure time are needed for understanding the complex nature of thyroid responses to perchlorate.     

Impact of smoking and thiocyanate on perchlorate and thyroid hormone associations in the 2001-2002 national health and nutrition examination survey

BACKGROUND: Findings from a recent large study suggest that perchlorate at commonly occurring exposure concentrations may decrease thyroid hormone levels in some women. Decreases in thyroid hormone seen with perchlorate exposure could be even greater in people with concomitant exposure to agents such as thiocyanate that may affect the thyroid by mechanisms similar to those of perchlorate. OBJECTIVES AND METHODS: We used data from the National Health and Nutrition Examination Survey to assess the impact of smoking and thiocyanate on the relationship between urinary per-chlorate and serum thyroxine (T(4)) and thyroid-stimulating hormone (TSH). RESULTS: In women with urinary iodine levels < 100 microg/L, the association between the logarithm of perchlorate and decreased T(4) was greater in smokers [regression coefficient (beta) = -1.66, p = 0.0005] than in nonsmokers (beta = -0.54, p = 0.04). In subjects with high, medium, and low cotinine levels, these regression coefficients were -1.47 (p = 0.0002), -0.57 (p = 0.03), and -0.16 (p = 0.59). For high, medium, and low thiocyanate tertiles they were -1.67 (p = 0.0009), -0.68 (p = 0.09), and -0.49 (p = 0.11). Clear interactions between perchlorate and smoking were not seen with TSH or with T(4) in women with urinary iodine levels > or = 100 microg/L or in men. CONCLUSIONS: These results suggest that thiocyanate in tobacco smoke and perchlorate interact in affecting thyroid function, and this effect can take place at commonly occurring perchlorate exposures. Agents other than tobacco smoke might cause similar interactions, and further research on these agents could help identify people who are particularly susceptible to perchlorate.     

Benchmark calculations for perchlorate from three human cohorts

The presence of low concentrations of perchlorate in some drinking water sources has led to concern regarding potential effects on the thyroid. In a recently published report, the National Academy of Sciences indicated that the perchlorate dose required to cause hypothyroidism in adults would probably be > 0.40 mg/kg-day for months or longer. In this study, we calculated benchmark doses for perchlorate from thyroid-stimulating hormone (TSH) and free thyroxine (T4) serum indicators from two occupational cohorts with long-term exposure to perchlorate, and from a clinical study of volunteers exposed to perchlorate for 2 weeks. The benchmark dose for a particular serum indicator was defined as the dose predicted to cause an additional 5 or 10% of persons to have a serum measurement outside of the normal range. Using the data from the clinical study, we estimated the half-life of perchlorate in serum at 7.5 hr and the volume of distribution at 0.34 L/kg. Using these estimates and measurements of perchlorate in serum or urine, doses in the occupational cohorts were estimated and used in benchmark calculations. Because none of the three studies found a significant effect of perchlorate on TSH or free T4, all of the benchmark dose estimates were indistinguishable from infinity. The lower 95% statistical confidence limits on benchmark doses estimated from a combined analysis of the two occupational studies ranged from 0.21 to 0.56 mg/kg-day for free T4 index and from 0.36 to 0.92 mg/kg-day for TSH. Corresponding estimates from the short-term clinical study were within these ranges.     

Effects of perchlorate exposure on resting metabolism, peak metabolism, and thyroid function in the prairie vole (Microtus ochrogaster)

Perchlorate, the oxidizer component in most solid rocket propellant formulations, is known to inhibit the uptake of iodide into the thyroid gland, thereby reducing production of the thyroid hormones, triiodothyronine and thyroxine (T4). Thyroid hormones regulate metabolism in endothermic organisms and are responsible for maintenance of homeothermic body temperatures. Little is known about the effects of perchlorate on metabolic capacity. The objectives of the present study were to determine if subchronic (51 d; 0, 1, and 10 mg/kg/d) and chronic (180 d; 0.75 mg/kg/d) perchlorate exposure in adult male prairie voles (Microtus ochrogaster) would alter resting metabolic rates as a result of decreased circulating thyroid hormone concentrations and to determine if perchlorate exposure disrupts thermogenesis in mammals exposed to cold stress. Voles exposed to perchlorate for 51 or 180 d experienced no significant alterations in resting metabolic rates at any point during the exposure period. Additionally, the treatment had no effect on peak metabolic rates or plasma thyroid hormone concentrations. However, thyroid gland T4 concentrations were significantly lower in perchlorate-exposed voles than in controls, indicating that thyroid gland T4 content may be a more sensitive endpoint than other thyroid variables for assessing perchlorate exposure. Overall, the present study did not provide evidence for energetic alterations associated with perchlorate exposure at concentrations that are higher than those typically found in groundwater or surface water in the environment.     

Novel biomarkers of perchlorate exposure in zebrafish

Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid hormone production. Although several effects of perchlorate on the thyroid system have been reported, the utility of these pathologies as markers of environmental perchlorate exposures has not been adequately assessed. The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates.     

Neonatal thyroxine level and perchlorate in drinking water

Environmental contamination of drinking water has been observed for perchlorate, a chemical able to affect thyroid function. This study examines whether that exposure affected the thyroid function of newborns. Neonatal blood thyroxine (T4) levels for days 1 to 4 of life were compared for newborns from the city of Las Vegas, Nevada, which has perchlorate in its drinking water, and those from the city of Reno, Nevada, which does not (detection limit, 4 micrograms/L [ppb]). This study is based on blood T4 analyses from more than 23,000 newborns in these two cities during the period April 1998 through June 1999. No difference was found in the mean blood T4 levels of the newborns from these two cities. Drinking water perchlorate levels measured monthly for Las Vegas ranged during this study period from non-detectable for 8 months to levels of 9 to 15 ppb for 7 months. Temporal differences in mean T4 level were noted in both cities but were unrelated to the perchlorate exposure. This study was sufficiently sensitive to detect the effects of gender, birth weight, and the day of life on which the blood sample was taken on the neonatal T4 level, but it detected no effect from environmental exposures to perchlorate that ranged up to 15 micrograms/L (ppb).     

Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat

BACKGROUND: Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. OBJECTIVES: The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. METHODS: Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. RESULTS: At the highest perchlorate dose, triiodothyronine (T(3)) and thyroxine (T(4)) were reduced in pups on postnatal day 21. T(4) in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T(4) were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T(3). Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. CONCLUSIONS: Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate.     

Effects of ammonium perchlorate on thyroid function in developing fathead minnows, Pimephales promelas

Perchlorate is a known environmental contaminant, largely due to widespread military use as a propellant. Perchlorate acts pharmacologically as a competitive inhibitor of thyroidal iodide uptake in mammals, but the impacts of perchlorate contamination in aquatic ecosystems and, in particular, the effects on fish are unclear. Our studies aimed to investigate the effects of concentrations of ammonium perchlorate that can occur in the environment (1, 10, and 100 mg/L) on the development of fathead minnows, Pimephales promelas. For these studies, exposures started with embryos of < 24-hr postfertilization and were terminated after 28 days. Serial sectioning of thyroid follicles showed thyroid hyperplasia with increased follicular epithelial cell height and reduced colloid in all groups of fish that had been exposed to perchlorate for 28 days, compared with control fish. Whole-body thyroxine (T4) content (a measure of total circulating T4 in fish exposed to 100 mg/L perchlorate was elevated compared with the T4 content of control fish, but 3,5,3-triiodothyronine (T3) content was not significantly affected in any exposure group. Despite the apparent regulation of T3, after 28 days of exposure to ammonium perchlorate, fish exposed to the two higher levels (10 and 100 mg/L) were developmentally retarded, with a lack of scales and poor pigmentation, and significantly lower wet weight and standard length than were control fish. Our study indicates that environmental levels of ammonium perchlorate affect thyroid function in fish and that in the early life stages these effects may be associated with developmental retardation.     

甘肃省人群高氯酸盐暴露水平及对甲状腺功能影响分析

  目的  对甘肃省人群高氯酸盐暴露水平进行评估并探讨其与甲状腺功能的关系,为该地区高氯酸盐污染防控提供依据。  方法  采用现况研究设计,选取兰州市城关区和定西市陇西县的随机两个社区中参与义诊的居民作为研究对象,采用问卷调查、体格检查和生化检查收集研究对象的基本资料及相关信息。应用多因素线性回归分析模型和限制性立方样条分析高氯酸盐暴露水平与甲状腺功能的关联及剂量-反应关系。  结果  本研究共纳入研究对象100名,包括男性48名和女性52名。尿高氯酸盐浓度的中位数(四分位间距)为23.90(13.30~43.54)μg/g Cr。多因素线性回归分析发现,调整混杂因素后,高氯酸盐暴露水平与血清总三碘甲状腺原氨酸(total triiodothyronine, TT3)、游离三碘甲状腺原氨酸(free triiodothyronine, FT3)和游离甲状腺素(free thyroxine, FT4)水平呈正相关趋势(均有P < 0.05)。限制性立方样条分析发现高氯酸盐暴露水平与血清TT3和FT4水平呈非线性剂量-反应关系(均有P < 0.05)。  结论  甘肃省地区人群的高氯酸盐暴露水平较高。高氯酸盐暴露水平与血清TT3、FT4水平有相关关联。     

Effects of exposure to polychlorinated biphenyls and organochlorine pesticides on thyroid function during pregnancy

In this study, the authors' objective was to determine whether serum concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene, p,p'-dichlorodiphenyl trichloroethane (DDT), o,p'-DDT, and p,p'-dichlorodiphenyl dichloroethylene (DDE) are associated with thyroid function during pregnancy. These compounds, as well as thyroid-stimulating hormone, total thyroxine, and free thyroxine, were measured in serum samples collected between October 1999 and October 2000 from 334 pregnant women living in the Salinas Valley, California. Data were analyzed by multivariate linear regression. After adjustment for covariates, seven of the 19 PCB congeners detected in more than 75% of participants and the sum of those congeners were negatively associated with free thyroxine concentrations. PCBs 44, 52, and 183 remained significant after the exclusion of two outliers. Hexachlorobenzene concentrations were negatively associated with both free thyroxine and total thyroxine. PCB and hexachlorobenzene concentrations were strongly correlated, which hampered the authors' ability to identify their independent associations with thyroid function. None of the exposures under study were associated with thyroid-stimulating hormone. Results suggest that exposure to PCBs and/or hexachlorobenzene at background levels may affect thyroid function during pregnancy. These findings are of particular significance, since thyroid hormones of maternal origin may play an essential role in fetal neurodevelopment.     

Proposal for the assessment of quantitative dermal exposure limits in occupational environments: Part 1. Development of a concept to derive a quantitative dermal occupational exposure limit

Dermal uptake of chemicals at the workplace may contribute considerably to the total internal exposure and so needs to be regulated. At present only qualitative warning signs--the "skin notations"--are available as instruments. An attempt was made to develop a quantitative dermal occupational exposure limit (DOEL) complementary to respiratory occupational exposure limits (OELs). The DOEL refers to the total dose deposited on the skin during a working shift. Based on available data and experience a theoretical procedure for the assessment of a DOEL was developed. A DOEL was derived for cyclophosphamide and 4,4-methylene dianiline (MDA) according to this procedure. The DOEL for MDA was tested for applicability in an actual occupational exposure scenario. An integrated approach is recommended for situations in which both dermal and respiratory exposures contribute considerably to the internal exposure of the worker. The starting point should be an internal health based occupational exposure limit--that is, the maximum dose to be absorbed without leading to adverse systemic effects. The proposed assessment of an external DOEL is then either based on absorption rate or absorption percentage. The estimation of skin penetration seems to be of crucial importance in this concept. If for a specific substance a maximal absorption rate can be estimated a maximal skin surface area to be exposed can be assessed which may then serve the purpose of a DOEL. As long as the actual skin surface exposed is smaller than this maximal skin surface area the internal OEL will not be exceeded, and therefore, no systemic health problems would be expected, independent of the dermal dose/unit area. If not, the DOEL may be interpreted as the product of dermal dose/unit area (mg/cm2) and exposed skin surface area (cm2). The proposed concept for a DOEL is relevant and can be made applicable for health surveillance in the occupational situation where dermal exposure contributes notably to the systemic exposure. Further research should show whether this concept is more generally applicable.

 

     

Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates

Polychlorinated biphenyls (PCBs) are industrially produced environmentally persistent compounds. In developed countries all humans have detectable levels in blood and other tissues. PCBs alter thyroid hormone metabolism in animal experiments, and human data suggest background-level exposure may have similar effects in neonates. We evaluated this possible effect among 160 North Carolina children whose in utero PCB exposure was estimated on the basis of the mother's PCB levels in milk and blood, in 1978-1982 (estimated median PCB level in milk at birth, 1.8 mg/kg lipid). Their umbilical cord sera were thawed in 1998 and assayed for total thyroxine, free thyroxine, and thyroid stimulating hormone. We found that PCB exposure was not strongly related to any of the thyroid measures. For example, for a one unit change in milk PCB concentration (mg/kg lipid), the associated multivariate-adjusted increase in thyroid stimulating hormone level was 7% (95% confidence limits (CL) = -6, 21). Despite the possibility of sample degradation, these data suggest that within the range of background-level exposure in the United States, in utero PCB exposure is only slightly related to serum concentration of total thyroxine, free thyroxine, and thyroid stimulating hormone at birth.     

Summary of measurements of employee exposure to airborne dust and fiber in sixteen facilities producing man-made mineral fibers.

The results of an industry-wide study to determine the exposure of workers to man-made mineral fibers are summarized. The purpose of the study was to determine current employee exposures to airborne fibers and to utilize results to estimate past exposures. Measured exposures of workers to airborne total particulate matter and fibers are presented; samples were evaluated by phase contrast and electron microscopy. Results of the three year study, which encompassed 16 facilities and over 1500 eight hour samples, show that although there is a wide variation in concentrations of airborne fibers and particulate matter between and within the facilities surveyed, the concentrations of airborne particulate matter and fibers are generally less than 2.5 mg/m3 and 0.5 fibers/cm3, respectively. The norminal fiber size of the fibers manufactured and average airborne fiber concentration were highly correlated.     

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens

Objective: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. Methods: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (<15, 15–24, 25–39, and ≥40 μ g/dl). Results: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T₄: 6.8 versus 6.1 μ g/dl), estimated free thyroxine (EFT₄: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T₄, EFT₄, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. Conclusion: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (<60 μ g/dl) of occupational lead exposure. Received: 3 August 1997 / Accepted: 8 July 1998     

Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States

BACKGROUND: Perchlorate is commonly found in the environment and known to inhibit thyroid function at high doses. Assessing the potential effect of low-level exposure to perchlorate on thyroid function is an area of ongoing research. OBJECTIVES: We evaluated the potential relationship between urinary levels of perchlorate and serum levels of thyroid stimulating hormone (TSH) and total thyroxine (T4) in 2,299 men and women, > or = 12 years of age, participating in the National Health and Nutrition Examination Survey (NHANES) during 2001-2002. METHODS: We used multiple regression models of T4 and TSH that included perchlorate and covariates known to be or likely to be associated with T4 or TSH levels: age, race/ethnicity, body mass index, estrogen use, menopausal status, pregnancy status, premenarche status, serum C-reactive protein, serum albumin, serum cotinine, hours of fasting, urinary thiocyanate, urinary nitrate, and selected medication groups. RESULTS: Perchlorate was not a significant predictor of T4 or TSH levels in men. For women overall, perchlorate was a significant predictor of both T4 and TSH. For women with urinary iodine < 100 microg/L, perchlorate was a significant negative predictor of T4 (p < 0.0001) and a positive predictor of TSH (p = 0.001). For women with urinary iodine > or = 100 microg/L, perchlorate was a significant positive predictor of TSH (p = 0.025) but not T4 (p = 0.550). CONCLUSIONS: These associations of perchlorate with T4 and TSH are coherent in direction and independent of other variables known to affect thyroid function, but are present at perchlorate exposure levels that were unanticipated based on previous studies.     

Perchlorate Exposure Induces Hypothyroidism and Affects Thyroid-Responsive Genes in Liver But Not Brain of Quail Chicks

Ground-dwelling birds in perchlorate-contaminated areas are exposed to perchlorate ion, a known thyroid disruptor, and might be vulnerable to the developmental effects of perchlorate-induced hypothyroidism. We hypothesized that perchlorate-induced hypothyroidism would alter the expression of thyroid-responsive genes involved in thyroid hormone (TH) regulation and in the development of target organ function. Japanese quail chicks were exposed to 2000 mg/L ammonium perchlorate in drinking water for 7.5 weeks beginning on day 5 posthatch. Hypothyroidism was evident after 2 weeks of exposure as lower plasma THs and lower TH content in exposed chicks than in controls. The degree of hypothyroidism was increased at 7.5 weeks, as indicated by significant thyroid gland hypertrophy and sustained changes in thyroid function. After 2 weeks of exposure, hypothyroidism increased type 2 5′-deiodinase (D2) mRNA level and decreased Spot 14 (SP14) mRNA level in the liver, whereas D2 mRNA and RC3 mRNA levels in brain were not affected. After 7.5 weeks of exposure, mRNA levels in the exposed group did not differ from those in controls in either the liver or brain, suggesting the responsiveness of these genes to THs decreased during development. These results suggest that the brain, but not the liver, was protected from the effects of hypothyroidism, probably by changes in D2 activity at the protein level and/or regulation of TH entry and exit from the brain. We concluded that perchlorate exposure caused hypothyroidism in young Japanese quail and affected the expression of thyroid-responsive genes during early posthatch development.     

Goitrogenic Anions,Thyroid-Stimulating Hormone,and Thyroid Hormone in Infants

Background

Environmental exposure of infants to perchlorate, thiocyanate, nitrate, might interfere with thyroid function. U.S. women with higher background perchlorate exposure have higher thyroid-stimulating hormone (TSH) and lower thyroxine (T₄). There are no studies with individual measures of thyroid function and these goitrogens available in infants.

Objective

We examined the association of urinary perchlorate, nitrate, iodide, and thiocyanate with urinary T₄ and TSH in infants and whether that association differed by sex or iodide status.

Methods

We used data and samples from the Study of Estrogen Activity and Development, which assessed hormone levels of full-term infants over the first 12 months of life. The study included 92 full-term infants between birth and 1 year of age seen up to four times. Perchlorate, thiocyanate, nitrate, and iodide were measured in 206 urine samples; TSH and T₄ and were measured in urines and in 50 blood samples.

Results

In separate mixed models, adjusting for creatinine, age, sex, and body mass index, infants with higher urinary perchlorate, nitrate or thiocyanate had higher urinary TSH. With all three modeled, children with higher nitrate and thiocyanate had higher TSH, but higher perchlorate was associated with TSH only in children with low iodide. Unexpectedly, exposure to the three chemicals was generally associated with higher T₄.

Conclusions

The association of perchlorate exposure with increased urinary TSH in infants with low urinary iodide is consistent with previous findings. Higher thiocyanate and nitrate exposure were also associated with higher TSH in infants.     

Does perchlorate in drinking water affect thyroid function in newborns or school-age children?

Perchlorate is known to suppress thyroid function by inhibiting uptake of iodide by the human thyroid at doses of 200 mg/day or greater. A study was conducted to investigate the potential effects of perchlorate in drinking water on thyroid function in newborns and school-age children. A total of 162 school-age children and 9784 newborns were studied in three proximate cities in northern Chile that have different concentrations of perchlorate in drinking water: Taltal (100 to 120 micrograms/L), Cha?aral (5 to 7 micrograms/L), and Antofagasta (non-detectable: < 4 micrograms/L). Among schoolchildren, no difference was found in thyroid-stimulating hormone levels or goiter prevalence among lifelong residents of Taltal or Cha?aral compared with those of Antofagasta, after adjusting for age, sex, and urinary iodine. No presumptive cases of congenital hypothyroidism were detected in Taltal or Cha?aral; seven cases were detected in Antofagasta. Neonatal thyroid-stimulating hormone levels were significantly lower in Taltal compared with Antofagasta; this is opposite to the known pharmacological effect of perchlorate, and the magnitude of difference did not seem to be clinically significant. These findings do not support the hypothesis that perchlorate in drinking water at concentrations as high as 100 to 120 micrograms/L suppresses thyroid function in newborns or school-age children.