Impact of Smoking and Thiocyanate on Perchlorate and Thyroid Hormone Associations in the 2001-2002 National Health and Nutrition Examination Survey

By Steinmaus, Craig; Miller, Mark D. et al. | Environmental Health Perspectives, September 2007 | Go to article overview

Impact of Smoking and Thiocyanate on Perchlorate and Thyroid Hormone Associations in the 2001-2002 National Health and Nutrition Examination Survey


Steinmaus, Craig, Miller, Mark D., Howd, Robert, Environmental Health Perspectives


Perchlorate has been used by the aerospace industry as an oxidizer in solid rocket propellant, slurry explosives, road flares, and air bag inflation systems. Human environmental exposure can occur through food or water after industrial contamination or from perchlorate that is naturally occurring. In a recent analysis of data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES), detectable levels of perchlorate were found in the urine of all 2,820 U.S. residents assessed (Blount et al. 2006b). Further analysis of the 2001-2002 NHANES data also identified an association between urinary levels of perchlorate and decreased levels of serum thyroxine ([T.sub.4]) in women with urinary iodine concentrations < 100 [micro]g/L (Blount et al. 2006a). A remarkable feature of this finding is that it was identified at perchlorate concentrations much lower than those linked to thyroid effects in any previous study. In fact, NHANES was designed to provide a nationally representative sample. Thus, the perchlorate exposure levels of the subjects in this study are likely similar to exposures occurring in a large portion of the U.S. population. Another notable feature was the relatively large fraction of women who had urinary iodine levels in the range where these effects were found. That is, 35% of all women [greater than or equal to] 12 years of age in NHANES 2001-2002 had urinary iodine levels < 100 [micro]g/L.

High doses of perchlorate have been shown to competitively inhibit iodide uptake in the thyroid gland, and perchlorate has been used therapeutically for this effect (Stanbury and Wyngaarden 1952; Wyngaarden et al. 1952). Other agents, including nitrate in food and water and thiocyanate in food or from tobacco smoke, also affect the thyroid by the same mechanism (Braverman et al. 2005; Tonacchera et al. 2004; Wyngaarden et al. 1953). Thiocyanate is a metabolite of cyanide found in tobacco smoke, and increased serum thiocyanate levels are associated with increasing levels of smoking (Foss and Lund-Larsen 1986). Thiocyanate is also found in some foods including cabbage, broccoli, cassava, and rapeseed oil (Foss and Lund-Larsen 1986).

In this investigation, we used data from the 2001-2002 NHANES to assess whether thiocyanate or other substances in tobacco smoke may interact with iodine and low levels of perchlorate in affecting [T.sub.4] and thyroidstimulating hormone (TSH) (National Center for Health Statistics 2002). The purpose of this investigation was to help increase our understanding of the mechanisms of perchlorate toxicity, to evaluate whether associations between perchlorate and thyroid hormones may differ between smokers and nonsmokers (or categories of cotinine and thiocyanate), and to help identify subpopulations that may be more susceptible than others to the thyroid effects of perchlorate. These issues could have tremendous public health significance given the large numbers of people who appear to be exposed to perchlorate and have low iodine intake. The recent finding linking low levels of urinary perchlorate to reduced thyroid function, and the possibility that even minor decrements in thyroid function could affect early-life cognitive development, highlight the potentially serious impact of perchlorate exposure.

Materials and Methods

NHANES is a national survey of health, nutrition, and sociodemographic information involving a complex multistage probability sampling design conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics (2002). In NHANES 2001-2002, levels of perchlorate, cotinine, and thiocyanate were analyzed in a representative one-third subsample of all subjects. For all subjects [greater than or equal to] 12 years of age, these data were combined with data on levels of serum [T.sub.4], serum TSH, smoking status, and other variables that might affect perchlorate- thyroid associations. These included race (Mexican American, other Hispanic, non- Hispanic white, non-Hispanic black, or other, each entered as a dichotomous variable), age (years), iodine status, serum albumin (grams per deciliter), body mass index (BMI) (kilograms per square meter), 24-hr caloric intake (kilocalories per day from 24-hr dietary recall data), pregnancy status (based on urinary pregnancy test results and self-reports), postmenopausal status (based on self-report, time since last period, and presence or absence of other reasons for missed menstruation), premenarche status (self-report), serum c-reactive protein (milligrams per deciliter), hours of fasting before serum collection (self-report), urinary nitrate (micrograms per liter), current lactation (dichotomous based on self-report), and use of medications known to affect the thyroid (e. …

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