Evaluation of ricinine, a ricin biomarker, from a non-lethal castor bean ingestion.

A case is presented of the attempted suicide of a 58-year-old man using castor beans. The patient came to the emergency room complaining of nausea, vomiting and diarrhea for nine hours following the ingestion of six castor beans. Urine samples were taken throughout the hospital stay and submitted to the Centers for Disease Control and Prevention for analysis of ricinine, a castor bean component. The samples were found to be positive for ricinine, with a maximum concentration of 674 µg/g-creatinine excreted approximately 23 h post-exposure. Subsequent samples demonstrated lower ricinine concentrations, with the final sample taken at 62 h post-exposure at a concentration of 135 µg/g-creatinine of ricinine. The estimated urinary excretion half-life was approximately 15 h and the recovery of ricinine in the urine over the three days was estimated to be less than 10%. The patient fully recovered with supportive care and was discharged from the hospital six days after admission.

Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12.

BACKGROUND: Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects. OBJECTIVE: The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency. DESIGN: Data from NHANES, a nationally representative cross-sectional survey, were examined for adults aged >19 y (mean ± SD age: 45 ± 1 y) from 1999 to 2004 (n = 12,612). RESULTS: Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of >148 pmol/L for vitamin B-12 and of ≤210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency. CONCLUSIONS: These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal.

Smoking status and urine cadmium above levels associated with subclinical renal effects in U.S. adults without chronic kidney disease.

Tobacco smoke is a major source of adult exposure to cadmium (Cd). Urine Cd levels (CdU) above 1.0, 0.7, and 0.5 µgCd/g creatinine have been associated with increased rates of microproteinuria and reduction in glomerular filtration rate. The two study objectives were to determine the prevalence and relative risk (RR) by smoking status for CdU above 1.0, 0.7, and 0.5 µgCd/g creatinine in U.S. adults; and to describe geometric mean CdU by smoking status, age, and sex. NHANES 1999-2006 data for adults without chronic kidney disease were used to compute prevalence rates above the three CdU in current and former cigarette smokers, and non-smokers. RRs for smokers adjusted for age and sex were computed by logistic regression. Analysis of covariance was used to calculate geometric means of CdU adjusted for age, sex, smoking status, log urine creatinine, and interaction terms: age-smoking status and sex-smoking status. At selected ages, adjusted RR for exceeding each risk-associated CdU was highest for current smokers (3-13 times), followed by former smokers (2-3 times), compared to non-smokers. Adjusted RR for smokers increased with age and was higher in females than males. Adjusted geometric means of CdUs increased with age, were higher in females than in males regardless of smoking status, and were higher in current smokers than former smokers, who had higher levels than non-smokers at any age. Cigarette smoking greatly increases RR of exceeding renal risk-associated CdU. Former smokers retain significant risk of exceeding these levels compared to non-smokers. CdU increased with age, particularly in current smokers.

Interpreting NHANES biomonitoring data, cadmium.

Cadmium (Cd) occurs naturally in the environment and the general population's exposure to it is predominantly through diet. Chronic Cd exposure is a public health concern because Cd is a known carcinogen; it accumulates in the body and causes kidney damage. The National Health and Nutritional Examination Survey (NHANES) has measured urinary Cd; the 2003-2004 NHANES survey cycle reported estimates for 2257 persons aged 6 years and older in the Fourth National Report on Human Exposure to Environmental Chemicals. As part of translational research to make computerized models accessible to health risk assessors we re-coded a cadmium model in Berkeley Madonna simulation language. This model was used in our computational toxicology laboratory to predict the urinary excretion of cadmium. The model simulated the NHANES-measured data very well from ages 6 to 60+ years. An unusual increase in Cd urinary excretion was observed among 6-11-year-olds, followed by a continuous monotonic rise into the seventh decade of life. This observation was also made in earlier studies that could be life stage-related and a function of anatomical and phsysiological changes occurring during this period of life. Urinary excretion of Cd was approximately twofold higher among females than males in all age groups. The model describes Cd's cumulative nature in humans and accommodates the observed variation in exposure/uptake over the course of a lifetime. Such models may be useful for interpreting biomonitoring data and risk assessment.

Postmortem blood cadmium, lead, and mercury concentrations: comparisons with regard to sampling location and reference ranges for living persons.

This study's goal was to determine cadmium (Cd), lead (Pb), total mercury (THg), and inorganic mercury (IHg) levels in human cadavers to compare measured levels with established reference ranges for living persons and to determine whether blood levels varied with time from death to sample collection or by body collection site. Subjects (n = 66) recruited from the Fulton County Medical Examiner's Office in Atlanta, GA, were 20 years of age or older, had no penetrating trauma, no obvious source of environmental contamination of the vasculature, and had whole blood accessible from the femoral (F) site, the cardiac (C) site, or both. Geometric mean results were as follows: 2.59 microg/L F-Cd; 11.81 microg/L C-Cd; 1.03 microg/L F-THg; 2.01 microg/L C-THg; 0.29 microg/L F-IHg; 0.49 microg/L C-IHg; 1.78 microg/dL F-Pb; and 1.87 microg/dL C-Pb. Both F- and C-Cd levels as well as C-THg levels were significantly higher than reference values among living persons (C- and F-Cd, p < 0.0001 and C-THg, p = 0.0001, respectively). Based on regression modeling, as the postmortem interval increased, blood Cd levels increased (p < 0.006). Postmortem blood Cd concentrations were elevated compared to population values and varied with respect to sampling location and postmortem interval.

Melamine toxicity.

Melamine contamination of infant formula in China and its health effects highlight the safety of the global food supply especially as it relates to formula-fed infants. Melamine is a widely used industrial chemical not considered acutely toxic with a high LD(50) in animals. The data available on acute and chronic human exposure to melamine have been limited and extrapolated from animal data. Pet food contamination in 2004 and 2007 showed stone formation and illness in animals when melamine was co-ingested with cyanuric acid. The recent outbreak in infants showed that melamine ingested in large doses may cause stones and illness without significant ingestion of cyanuric acid or other melamine-related chemicals. This may be due to increased uric acid excretion in infants and formation of melamine-uric acid stones. Diagnosis and treatment of infants exposed to melamine requires further study. Clinical signs and symptoms in infants are nonspecific. The stones may be radiolucent and are not consistently seen on ultrasound. The use of alkalinization of the urine for treatment has been proposed, but is of unproven benefit. The FDA and other regulatory agencies have recommended acceptable levels of melamine in foods for consumption. Melamine ingestion has been implicated in stone formation when co-ingested with cyanuric acid, but will cause urinary stones in infants when large amounts of melamine alone are ingested.

Exposure of the U.S. population to acrylamide in the National Health and Nutrition Examination Survey 2003-2004.

BACKGROUND: The lifelong exposure of the population to acrylamide has raised concerns about the possible health effects of the chemical. Data on the extent of exposure to acrylamide and its primary metabolite, glycidamide, are needed to aid in the assessment of potential health effects. OBJECTIVES: The aim of this study was to assess human exposure to acrylamide and glycidamide in the general U.S. population through the measurement of hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA). METHODS: HbAA and HbGA were measured in 7,166 subjects from the National Health and Nutrition Examination Survey. Stratified HbAA and HbGA data were reported by sex, age groups, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white), and smoking status based on serum cotinine levels. Covariate-adjusted geometric means for each demographic group were calculated using multiple regression analysis. RESULTS: HbAA and HbGA levels ranged from 3 to 910 and from 4 to 756 pmol/g hemoglobin, respectively, with smokers having the highest levels overall. Tobacco smoke exposure in nonsmokers had a small but significant effect on HbAA and HbGA levels. Adjusted geometric mean levels for children 311 years of age were higher than for adults >or= 60 years of age [mean (95% confidence interval): HbAA, 54.5 (49.1-51.5) and HbGA, 73.9 (71.3-76.6) vs. HbAA, 46.2 (44.3-48.2) and HbGA, 41.8 (38.7-45.2)]. Levels were highest in Mexican Americans [HbAA: 54.8 (51.9-57.8), HbGA: 57.9 (53.7-62.5)], whereas non-Hispanic blacks had the lowest HbGA levels [43.5 (41.1-45.9)]. CONCLUSIONS: U.S. population levels of acrylamide and glycidamide adducts are described. The high variability among individuals but modest differences between population subgroups suggest that sex, age, and race/ethnicity do not strongly affect acrylamide exposure. Adduct concentration data can be used to estimate relative exposure and to validate intake estimates.

Total blood mercury concentrations in the U.S. population: 1999-2006.

We describe the distribution and demographic characteristics of total blood Hg levels in the U.S. general population among persons ages 1 year and older who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES). We also describe trends in the total blood Hg of children ages 1-5 (n=3456) and females ages 16-49 during 1999-2006 (n=7245). In the combined 2003-2006 survey periods, the geometric means for non-Hispanic blacks, 0.853microg/L (95% confidence interval [CI], 0.766-0.950microg/L), and non-Hispanic whites, 0.833microg/L (95% CI, 0.752-0.922microg/L), were higher than the geometric mean for Mexican Americans, 0.580microg/L (95% CI, 0.522-0.645microg/L). Also in 2003-2006, regression analysis of log total blood Hg with age, race/ethnicity and gender showed that total blood Hg levels in the population exhibited a quadratic increase with age (p<0.0001), peaking at ages 50-59 in non-Hispanic blacks and whites, at ages 40-49 in Mexican Americans, and then declining at older ages. Over the four survey periods (1999-2006), regression analysis showed that total blood Hg levels increased slightly for non-Hispanic white children and decreased slightly for non-Hispanic black and Mexican American children. Over the same four survey periods, female children had slightly higher total blood Hg levels than males (0.356 vs. 0.313microg/L, p=0.0050) and total blood Hg levels in non-Hispanic black women aged 16-49 years were significantly higher than in non-Hispanic white women (1.081 vs. 0.850microg/L, p<0.0001) and in Mexican American women (1.081 vs. 0.70microg/L, p<0.0001).

Levels in the U.S. population of those persistent organic pollutants (2003-2004) included in the Stockholm Convention or in other long range transboundary air pollution agreements.

We report human serum levels of selected persistent organic pollutants (POPs) categorized by age, sex, and race/ ethnicity from a statistically representative sampling of the U.S. population during 2003 and 2004. The serum levels are for several chemicals listed in the Stockholm Convention on Persistent Organic Pollutants, in the Geneva Convention on Long-Range Transboundary Air Pollution, or in both. Population data for each chemical are described by geometric means and percentiles and are categorized by age, sex, and race/ ethnicity. At the 90th and 95th percentile, the dioxin total toxic equivalency (TEQ), using the 2005 toxic equivalency factors (TEFs) for all persons 12 years of age and older was 30.9 pg/g lipid (95% confidence interval (CI): 28.2-33.9 pg/g lipid) and 37.8 pg/g lipid (95% CI: 35.3-43.4 pg/g lipid), respectively. At both the 90th and 95th percentiles total TEQ increased significantly with increasing age. The population geometric mean (GM) for the total PCB concentration (sum of 35 congeners) for all persons 12 years of age and older was 0.820 ng/g whole-weight (95% CI: 0.782-0.863 ng/g whole-weight) and 134.4 ng/g lipid (95% CI: 128.9-140.0 ng/g lipid). The population 95th percentile for the total PCB concentration for all persons 12 years of age and older was 3.53 ng/g whole-weight (95% CI: 3.23-3.92 ng/g whole-weight) and 531 ng/g lipid (95% CI: 498-570 ng/g lipid). The concentrations of aldrin, endrin, gamma-HCH, and o,p'-DDT were

Urine mercury excretion following meso-dimercaptosuccinic acid challenge in fish eaters.

CONTEXT: Public awareness of methylmercury in fish has caused patients to seek testing for mercury poisoning. In some patients, the diagnosis of mercury poisoning has been made based on urine mercury excretions following oral dosing of meso-dimercaptosuccinic acid (DMSA), a metal chelator. However, studies comparing urine mercury excretion following DMSA in healthy non-fish eaters with healthy fish eaters could not be located. OBJECTIVES: To describe urinary mercury excretion before and after DMSA in healthy fish eaters and non-fish eaters, and to determine whether urine mercury excretion after DMSA would rise above baseline levels to a greater extent in fish eaters. DESIGN: A total of 24 healthy physicians were assigned to 1 of 3 groups based on fish consumption: non-fish eaters; 1 to 2 fish servings per week; and 3 or more servings per week. Blood mercury concentrations and 12-hour urine mercury and creatinine excretions were measured before and after oral ingestion of 30 mg of DMSA per kilogram of body weight. RESULTS: A total of 24 subjects completed the study, and 2 subsequently were excluded. No difference in baseline urinary mercury excretion was detected between groups. All groups demonstrated an increase in urinary mercury excretion following DMSA, which was higher in fish eaters (P = .04). Multiple linear regression found that the best predictor of a rise in urine mercury excretion following DMSA challenge was the prechelation blood mercury concentration. CONCLUSIONS: In this study of healthy physicians, oral DMSA produced a rise in urine mercury excretion both in non-fish eaters and fish eaters. The increase in chelated mercury excretion was higher in fish eaters. A simple rise in chelated mercury excretion over baseline excretion is not a reliable diagnostic indicator of mercury poisoning.

Levels of urinary total and speciated arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004.

OBJECTIVE: To provide levels of total and speciated urinary arsenic in a representative sample of the US population. METHODS: For the first time, total arsenic and seven inorganic and organic arsenic species were measured in the urine of participants (n=2557) for the 2003-2004 National Health and Nutrition Examination Survey (NHANES). Data were compiled as geometric means and selected percentiles of urinary arsenic concentrations (microg/l) and creatinine-corrected urinary arsenic (microg/g creatinine) for total arsenic, dimethylarsinic acid, arsenobetaine, and a sum of the inorganic related species. RESULTS: Arsenic acid, arsenous acid, arsenocholine, and trimethylarsine oxide were detected in 7.6%, 4.6%, 1.8%, and 0.3% of the participants, respectively (the limits of detection of 0.6-1.2 microg/l). Monomethylarsonic acid was detected in 35% of the overall population. For all participants aged > or =6 years, dimethylarsinic acid (geometric mean of 3.71 microg/l) and arsenobetaine (geometric mean of 1.55 microg/l) had the greatest contribution to the total urinary arsenic levels. A relatively greater percentage contribution from arsenobetaine is seen at higher total urinary arsenic levels and from dimethylarsinic acid at lower total urinary arsenic levels. For all participants aged > or =6 years, the 95th percentiles for total urinary arsenic and the sum of inorganic-related arsenic (arsenic acid, arsenous acid, dimethylarsinic acid, and monomethylarsonic acid) were 65.4 and 18.9 microg/l, respectively. For total arsenic and dimethylarsinic acid, covariate-adjusted geometric means demonstrated several slight differences due to age, gender, and race/ethnicity. CONCLUSIONS: The data reflect relative background contributions of inorganic and seafood-related arsenic exposures in the US population. Arsenobetaine and dimethylarsinic acid are the major arsenic species present with arsenobetaine, accounting for a greater proportion of total arsenic as total arsenic levels increase.

Outbreak of acute renal failure in Panama in 2006: a case-control study.

OBJECTIVE: In September 2006, a Panamanian physician reported an unusual number of patients with unexplained acute renal failure frequently accompanied by severe neurological dysfunction. Twelve (57%) of 21 patients had died of the illness. This paper describes the investigation into the cause of the illness and the source of the outbreak. METHODS: Case-control and laboratory investigations were implemented. Case patients (with acute renal failure of unknown etiology and serum creatinine > 2 mg/dl) were individually matched to hospitalized controls for age (+/- 5 years), sex and admission date (< 2 days before the case patient). Questionnaire and biological data were collected. The main outcome measure was the odds of ingesting prescription cough syrup in cases and controls. FINDINGS: Forty-two case patients and 140 control patients participated. The median age of cases was 68 years (range: 25-91 years); 64% were male. After controlling for pre-existing hypertension and renal disease and the use of angiotensin-converting enzyme inhibitors, a significant association was found between ingestion of prescription cough syrup and illness onset (adjusted odds ratio: 31.0, 95% confidence interval: 6.93-138). Laboratory analyses confirmed the presence of diethylene glycol (DEG) in biological samples from case patients, 8% DEG contamination in cough syrup samples and 22% contamination in the glycerin used to prepare the cough syrup. CONCLUSION: The source of the outbreak was DEG-contaminated cough syrup. This investigation led to the recall of approximately 60 000 bottles of contaminated cough syrup, widespread screening of potentially exposed consumers and treatment of over 100 affected patients.

Trends in circulating concentrations of total homocysteine among US adolescents and adults: findings from the 1991-1994 and 1999-2004 National Health and Nutrition Examination Surveys.

BACKGROUND: The National Health and Nutrition Examination Survey (NHANES) has monitored total homocysteine (tHcy) concentrations in a nationally-representative sample of the US population since 1991. Until recently, however, data could not be compared across survey periods because of changes in analytical methods and specimen matrices. Such an analysis of these data could supplement current knowledge regarding whether the US folic acid fortification program has modified national plasma tHcy concentrations. METHODS: We examined tHcy data in the prefortification NHANES III survey (phase II, 1991-1994) and in 3 postfortification survey periods (1999-2000, 2001-2002, and 2003-2004). We applied method adjustment equations to the survey data based on method comparison studies of separate samples. Persons with chronic kidney disease were excluded from the analyses. RESULTS: Mean plasma tHcy concentrations decreased by 8%, 9%, and 10% for adolescent, adult, and older men and by 6%, 3%, and 13% for women, respectively, from before to after fortification. Concentrations remained unchanged between the first and third postfortification survey periods. Prevalence estimates of increased plasma tHcy concentrations (>13 micromol/L) for older men and women decreased from prefortification (32% and 20%, respectively) to postfortification (14% and 5%, respectively) but remained unchanged thereafter (16% and 14%, respectively [males] and 5% and 9%, respectively [females]). CONCLUSIONS: After adjusting for method changes, we quantified a prefortification to postfortification decrease in circulating tHcy concentrations of about 10% in a national sample of the US population. This change is similar to effects seen in intervention trials with folic acid and in smaller observational studies.

Trends in blood folate and vitamin B-12 concentrations in the United States, 1988 2004.

BACKGROUND: Monitoring the folate status of US population groups over time has been a public health priority for the past 2 decades, and the focus has been enhanced since the implementation of a folic acid fortification program in the mid-1990s. OBJECTIVE: We aimed to determine how population concentrations of serum and red blood cell (RBC) folate and serum vitamin B-12 have changed over the past 2 decades. DESIGN: Measurement of blood indicators of folate and vitamin B-12 status was conducted in approximately 23,000 participants in the prefortification third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) and in approximately 8000 participants in 3 postfortification NHANES periods (together covering 1999-2004). RESULTS: Serum and RBC folate concentrations increased substantially (by 119-161% and 44-64%, respectively) in each age group in the first postfortification survey period and then declined slightly (by 5-13% and 6-9%, respectively) in most age groups between the first and third postfortification survey periods. Serum vitamin B-12 concentrations did not change appreciably. Prevalence estimates of low serum and RBC folate concentrations declined in women of childbearing age from before to after fortification (from 21% to <1% and from 38% to 5%, respectively) but remained unchanged thereafter. Prevalence estimates of high serum folate concentrations increased in children and older persons from before to after fortification (from 5% to 42% and from 7% to 38%, respectively) but decreased later after fortification. CONCLUSIONS: The decrease in folate concentrations observed longer after fortification is small compared with the increase soon after the introduction of fortification. The decrease is not at the low end of concentrations and therefore does not raise concerns about inadequate status.

Investigating childhood leukemia in Churchill County, Nevada.

BACKGROUND: Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide cancer rate, fewer than two cases would be expected. OBJECTIVES: In March 2001, the Centers for Disease Control and Prevention led federal, state, and local agencies in a cross-sectional, case-comparison study to determine if ongoing environmental exposures posed a health risk to residents and to compare levels of contaminants in environmental and biologic samples collected from participating families. METHODS: Surveys with more than 500 variables were administered to 205 people in 69 families. Blood, urine, and cheek cell samples were collected and analyzed for 139 chemicals, eight viral markers, and several genetic polymorphisms. Air, water, soil, and dust samples were collected from almost 80 homes to measure more than 200 chemicals. RESULTS: The scope of this cancer cluster investigation exceeded any previous study of pediatric leukemia. Nonetheless, no exposure consistent with leukemia risk was identified. Overall, tungsten and arsenic levels in urine and water samples were significantly higher than national comparison values; however, levels were similar among case and comparison groups. CONCLUSIONS: Although the cases in this cancer cluster may in fact have a common etiology, their small number and the length of time between diagnosis and our exposure assessment lessen the ability to find an association between leukemia and environmental exposures. Given the limitations of individual cancer cluster investigations, it may prove more efficient to pool laboratory and questionnaire data from similar leukemia clusters.

Perchlorate exposure of the US Population, 2001-2002.

Perchlorate is commonly found in the environment and can impair thyroid function at pharmacological doses. As a result of the potential for widespread human exposure to this biologically active chemical, we assessed perchlorate exposure in a nationally representative population of 2,820 US residents, ages 6 years and older, during 2001 and 2002 as part of the National Health and Nutrition Examination Survey (NHANES). We found detectable levels of perchlorate (>0.05 microg/l) in all 2,820 urine samples tested, indicating widespread human exposure to perchlorate. Urinary perchlorate levels were distributed in a log normal fashion with a median of 3.6 microg/l (3.38 microg/g creatinine) and a 95th percentile of 14 microg/l (12.7 microg/g creatinine). When geometric means of urinary perchlorate levels were adjusted for age, fasting, sex and race-ethnicity, we found significantly higher levels of urinary perchlorate in children compared with adolescents and adults. We estimated total daily perchlorate dose for each adult (ages 20 years and older), based on urinary perchlorate, urinary creatinine concentration and physiological parameters predictive of creatinine excretion rate. The 95th percentile of the distribution of estimated daily perchlorate doses in the adult population was 0.234 microg/kg-day [CI 0.202-0.268 microg/kg-day] and is below the EPA reference dose (0.7 microg/kg-day), a dose estimated to be without appreciable risk of adverse effects during a lifetime of exposure. These data provide the first population-based assessment of the magnitude and prevalence of perchlorate exposure in the US.

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.