Regression analysis was used to estimate and test for relationships between the blood lead concentration and the concentrations of serum thyroid stimulating hormone and serum total thyroxine in adults, 20 years and older, participating in the third National Health and Nutrition Examination Survey. No relationship was found between the blood lead level and the concentration of serum thyroid stimulating hormone. The serum total thyroxine concentration decreased as the blood lead level increased in women, but not in men. The lowest concentration of blood lead at which a relationship could be detected was 2.1 μg/dL and 3.9 μg/dL for the non-pregnant and pregnant women, respectively. Hypothetical mechanisms of the action of lead are discussed.

Essentially all women are exposed to polycyclic aromatic hydrocarbons (PAHs), formed during incomplete combustion of organic materials, including fossil fuels, wood, foods, and tobacco. PAHs are ovarian toxicants in rodents, and cigarette smoking is associated with reproductive abnormalities in women. Biomonitoring of hydroxylated PAH (OH-PAH) metabolites in urine provides an integrated measure of exposure to PAHs via multiple routes and has been used to characterize exposure to PAHs in humans. We hypothesized that concentrations of OH-PAHs in urine are associated with reproductive function in women. We recruited women 18-44years old, living in Orange County, California to conduct daily measurement of urinary luteinizing hormone (LH) and estrone 3-glucuronide (E13G) using a microelectronic fertility monitor for multiple menstrual cycles; these data were used to calculate endocrine endpoints. Participants also collected urine samples on cycle day 10 for measurement of nine OH-PAHs. Models were constructed for eight endpoints using a Bayesian mixed modeling approach with subject-specific random effects allowing each participant to act as a baseline for her set of measurements. We observed associations between individual OH-PAH concentrations and follicular phase length, follicular phase LH and E13G concentrations, preovulatory LH surge concentrations, and periovulatory E13G slope and concentration. We have demonstrated the feasibility of using urinary reproductive hormone data obtained via fertility monitors to calculate endocrine endpoints for epidemiological studies of ovarian function during multiple menstrual cycles. The results show that environmental exposure to PAHs is associated with changes in endocrine markers of ovarian function in women in a PAH-specific manner.

INTRODUCTION: Investigations of the effects of occupational exposure to lead on the concentrations of thyroid hormones in the blood have not produced consistent results. A meta-analysis was performed to assess the effect of occupational exposure to lead on thyroid hormone concentrations using the results from published studies. METHODS: Group means from studies of the thyroid function of persons occupationally exposed to lead were used in a meta-analysis. Differences between the control and exposed groups, and the slopes between thyroid hormone concentrations and log10 blood lead concentrations or duration of exposure to lead were estimated using mixed models. The hormones analyzed were thyroid stimulating hormone, total and free thyroxine, and total and free triiodothyronine. RESULTS: No differences in mean thyroid hormone concentrations were found between the exposed and control groups. No relationships were found between blood lead or the duration of exposure to lead and thyroid hormone concentrations. CONCLUSION: The results of the analysis do not provide evidence for an effect of occupational lead exposure on thyroid function in men. Am. J. Ind. Med. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Persistent organohalogens (POHs) and metals have been linked to alterations in menstrual cycle function and fertility in humans. The Cree First Nations people living near James Bay in Ontario and Quebec, Canada, have elevated levels of POHs, mercury and lead compared to other Canadians. The present study examines the interrelationships between selected POHs and elements on menstrual cycle function in these Cree women. Menstrual cycle characteristics were derived from structured daily diaries and endocrine measurements from daily urine samples collected during one cycle for 42 women age 19-42. We measured 31 POHs in blood plasma and 18 elements in whole blood, for 31 of the participants. POHs and elements detected in ≥70% of the participants were transformed by principal component (PC) analysis to reduce the contaminant exposure data to fewer, uncorrelated PCA variables. Multiple regression analysis revealed that, after adjusting for confounders, PC-3 values showed significant negative association with cycle length, after adjusting for confounders (p = 0.002). PC-3 accounted for 9.2% of the variance and shows positive loadings for cadmium, selenium, and PBDE congeners 47 and 153, and a negative loading for copper. Sensitivity analysis of the model to quantify likely effect sizes showed a range of menstrual cycle length from 25.3 to 28.3 days using the lower and upper 95% confidence limits of mean measured contaminant concentrations to predict cycle length. Our observations support the hypothesis that the menstrual cycle function of these women may be altered by exposure to POHs and elements from their environment.

BACKGROUND: For 15 months in 1981-1982, the commercial milk supply on the Hawaiian island of Oahu was contaminated with heptachlor epoxide, a metabolite of the insecticide heptachlor, resulting in gestational and/or lactational exposure to offspring of women who drank cow milk during that period. OBJECTIVE: To determine whether gestational and lactational exposure to heptachlor epoxide alters reproductive function and age at puberty in men or women. METHODS: 457 participants were recruited from a prior high school enrollment sampling frame of 20,000 adults born during 1981-1982 who lived on Oahu since at least first grade. Number of glasses of cow milk consumed weekly by the mother during the participant's gestation was used as a surrogate measure of heptachlor epoxide exposure. Reproductive function measures included semen analyses; reproductive hormones or their metabolites in daily urine specimens for one menstrual cycle; serum reproductive hormone levels in both sexes; and reported ages of onset for pubertal milestones. RESULTS: We observed no strong associations of heptachlor epoxide exposure during gestation and lactation with reproductive endpoints. In females, heptachlor epoxide exposure was associated with longer luteal phase length and slower drop in the ratio of estradiol to progesterone metabolites after ovulation. In males, heptachlor epoxide exposure was weakly associated with higher serum follicle stimulating hormone and luteinizing hormone concentrations, but no dose-response relationship was apparent. CONCLUSIONS: The results provide limited evidence that gestational and lactational exposure to heptachlor epoxide, due to milk contamination on Oahu in 1981-1982, resulted in clinically significant disturbances of reproductive function in men or women.

Regression analysis was used to estimate and test for relationships between urinary pesticide metabolites and neurobehavioral test performance in adults, 20 to 59 years old, participating in the third National Health and Nutrition Examination Survey. The 12 pesticide metabolites included 2 naphthols, 8 phenols, a phenoxyacetic acid, and a pyridinol. The 3 neurobehavioral tests included in the survey were simple reaction time, symbol-digit substitution, and serial digit learning. As the 2,4-dichlorophenol, 2,5-dichlorophenol, and the pentachlorophenol concentrations increased, performance on the serial digit learning test improved. As the 2,5-dichlorophenol concentration increased, performance on the symbol-digit substitution test improved. At low concentrations, the parent compounds of these metabolites may act at acetylcholine and gamma-aminobutyric acid synapses in the central nervous system to improve neurobehavioral test performance.

CONTEXT: Reproductive function may improve after bariatric surgery, although the mechanisms and time-related changes are unclear. OBJECTIVE: The objective of the study was to determine whether ovulation frequency/quality as well as associated reproductive parameters improve after Roux en Y gastric bypass surgery. DESIGN: This was a prospective cohort study that enrolled female subjects from 2005 to 2008 with study visits at baseline and then 1, 3, 6, 12, and up to 24 months after surgery. SETTING: The study was conducted at an academic health center. PATIENTS: Twenty-nine obese, reproductive-aged women not using confounding medications participated in the study. MAIN OUTCOME MEASURES: The primary outcome was integrated levels of urinary progestin (pregnanediol 3-glururonide) from daily urinary collections at 12 months postoperatively. Secondary outcomes were changes in vaginal bleeding, other biometric, hormonal, ultrasound, dual-energy x-ray absorptiometry measures, and Female Sexual Function Index. RESULTS: Ninety percent of patients with morbid obesity had ovulatory cycles at baseline, and the ovulatory frequency and luteal phase quality (based on integrated pregnanediol 3-glururonide levels) were not modified by bariatric surgery. The follicular phase was shorter postoperatively [6.5 d shorter at 3 months and 7.9-8.9 d shorter at 6-24 months (P < 0.01)]. Biochemical hyperandrogenism improved, largely due to an immediate postoperative increase in serum SHBG levels(P < 0.01), with no change in clinical hyperandrogenism (sebum production, acne, hirsutism). Bone density was preserved, contrasting with a significant loss of lean muscle mass and fat (P < 0.001), reflecting preferential abdominal fat loss (P < 0.001). Female sexual function improved 28% (P = 0.02) by 12 months. CONCLUSIONS: Ovulation persists despite morbid obesity and the changes from bypass surgery. Reproductive function after surgery is characterized by a shortened follicular phase and improved female sexual function.

A study of workers exposed to jet fuel propellant 8 (JP-8) was conducted at U.S. Air Force bases and included the evaluation of three biomarkers of exposure: S-benzylmercapturic acid (BMA), S-phenylmercapturic acid (PMA), and (2-methoxyethoxy)acetic acid (MEAA). Postshift urine specimens were collected from various personnel categorized as high (n = 98), moderate (n = 38) and low (n = 61) JP-8 exposure based on work activities. BMA and PMA urinary levels were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and MEAA urinary levels were determined by gas chromatography-mass spectrometry (GC-MS). The numbers of samples determined as positive for the presence of the BMA biomarker (above the test method's limit of detection [LOD = 0.5 ng/ml]) were 96 (98.0%), 37 (97.4%), and 58 (95.1%) for the high, moderate, and low (control) exposure workgroup categories, respectively. The numbers of samples determined as positive for the presence of the PMA biomarker (LOD = 0.5 ng/ml) were 33 (33.7%), 9 (23.7%), and 12 (19.7%) for the high, moderate, and low exposure categories. The numbers of samples determined as positive for the presence of the MEAA biomarker (LOD = 0.1 mcg/ml) were 92 (93.4%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure categories. Statistical analysis of the mean levels of the analytes demonstrated MEAA to be the most accurate or appropriate biomarker for JP-8 exposure using urinary concentrations either adjusted or not adjusted for creatinine; mean levels of BMA and PMA were not statistically significant between workgroup categories after adjusting for creatinine.

PURPOSE: To demonstrate the utility of the urinary metabolite (2-methoxyethoxy)acetic acid (MEAA) as a biomarker of exposure. 2-(2-methoxyethoxy)ethanol [diethylene glycol monomethyl ether] is an anti-icing agent used in the formulation of JP-8, and it is added at a known uniform 0.1% (v/v) concentration to each batch lot. JP-8 is a kerosene-based fuel containing different compounds that vary in the content of every batch/lot of fuel; thus, MEAA has the potential to be a more specific and a consistent quantitative biomarker for JP-8 exposure. METHODS: MEAA was used to measure exposure of jet propulsion fuel 8 (JP-8) in United States Air Force (USAF) personnel working at six airbases within the United States. Post-shift urine specimens from various personnel including high (n = 98), moderate (n = 38), and low (n = 61) exposure workgroup categories were collected and analyzed by a gas chromatographic-mass spectrometric test method. The three exposure groups were evaluated for the number per group positive for MEAA, and a statistical analysis consisted of pair-wise t-tests for unequal variances was used to test for the differences in mean MEAA concentrations between the exposure groups. RESULTS: The number of samples detected as positive for MEAA exposure, that is, those above the test method's limit of detection (LOD = 0.1 mcg/ml), were 92 (93.9%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure workgroup categories, respectively. The mean urinary MEAA level was significantly greater in the high exposure category (6.8 mcg/ml), compared to the moderate (0.42 mcg/ml) and the low (0.07 mcg/ml) exposure categories. The maximum concentration of urinary MEAA was 110 mcg/ml for the high exposure category, while 4.8 mcg/ml and 0.2 mcg/ml maximum levels were found in the moderate and low exposure categories, respectively. CONCLUSION: This study demonstrated that urinary MEAA can be used as an accurate biomarker of exposure for JP-8 workers and clearly distinguished the differences in JP-8 exposure by workgroup category.

The relationships between blood lead levels and serum follicle stimulating hormone and luteinizing hormone were assessed in a nationally representative sample of women, 35-60 years old, from the National Health and Nutrition Examination Survey 1999-2002. The blood lead levels of the women ranged from 0.2 to 17.0mcg/dL. The estimated geometric mean was 1.4mcg/dL, and the estimated arithmetic mean was 1.6mcg/dL. As the blood lead level increased, the concentration of serum follicle stimulating hormone increased in post-menopausal women, women who had both ovaries removed, and pre-menopausal women. The concentration of luteinizing hormone increased as blood lead level increased in post-menopausal women and women who had both ovaries removed. The lowest concentrations of blood lead at which a relationship was detected were 0.9mcg/dL for follicle stimulating hormone and 3.2mcg/dL for luteinizing hormone. Lead may act directly or indirectly at ovarian and non-ovarian sites to increase the concentrations of follicle stimulating hormone and luteinizing hormone.

OBJECTIVE: This study evaluated health care worker exposure to antineoplastic drugs. METHODS: A cross-sectional study examined environmental samples from pharmacy and nursing areas. A 6-week diary documented tasks involving those drugs. Urine was analyzed for two specific drugs, and blood samples were analyzed by the comet assay. RESULTS: Sixty-eight exposed and 53 nonexposed workers were studied. Exposed workers recorded 10,000 drug-handling events during the 6-week period. Sixty percent of wipe samples were positive for at least one of the five drugs measured. Cyclophosphamide was most commonly detected, followed by 5-fluorouracil. Three of the 68 urine samples were positive for one drug. No genetic damage was detected in exposed workers using the comet assay. CONCLUSIONS: Despite following recommended safe-handling practices, workplace contamination with antineoplastic drugs in pharmacy and nursing areas continues at these locations.

The relationship between the blood lead concentration and cognitive function in children and adults with different VDR genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16years old, performance on the digit span and arithmetic tests as a function of the blood lead concentration varied by VDR rs2239185 and VDR rs731236 genotypes. Decreases in performance occurred in some genotypes, but not in others. In adults 20 to 59years old, performance on the symbol-digit substitution test as a function of the blood lead concentration varied by VDR rs2239185-rs731236 haplotype. In the 12 to 16year old children and adults 60 or more years old, the relationship between the serum homocysteine and blood lead concentrations varied by VDR genotype. The mean blood lead concentrations of the children and adults did not vary by VDR genotype.

The relationship between the blood lead concentration and cognitive function in children and adults with different ALAD genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16 years old, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. In adults 20 to 59 years old, mean reaction time decreased as the blood lead concentration increased in the ALAD rs1800435 CC/CG group. This represents an improvement in performance. In adults 60 years and older, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. The serum homocysteine concentration increased as the blood lead concentration increased in adults 20 to 59 years old and 60 years and older, but there were no differences between genotypes. The mean blood lead concentration of children with the ALAD rs1800435 CC/CG genotype was less than that of children with the GG genotype.