BackgroundPhthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human males has been associated with increased prevalence of obesity, insulin resistance, and diabetes.ObjectivesOur objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance.MethodsSubjects were adult U.S. male participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. We modeled six phthalate metabolites with prevalent exposure and known or suspected antiandrogenic activity as predictors of waist circumference and log-transformed homeostatic model assessment (HOMA; a measure of insulin resistance) using multiple linear regression, adjusted for age, race/ethnicity, fat and total calorie consumption, physical activity level, serum cotinine, and urine creatinine (model 1); and adjusted for model 1 covariates plus measures of renal and hepatic function (model 2). Metabolites were mono-butyl phthalates (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl)-hexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP).ResultsIn model 1, four metabolites were associated with increased waist circumference (MBzP, MEHHP, MEOHP, and MEP; p-values ≤ 0.013) and three with increased HOMA (MBP, MBzP, and MEP; p-values ≤ 0.011). When we also adjusted for renal and hepatic function, parameter estimates declined but all significant results remained so except HOMA-MBP.ConclusionsIn this national cross-section of U.S. men, concentrations of several prevalent phthalate metabolites showed statistically significant correlations with abdominal obesity and insulin resistance. If confirmed by longitudinal studies, our findings would suggest that exposure to these phthalates may contribute to the population burden of obesity, insulin resistance, and related clinical disorders.

BackgroundIt is commonly stated in the literature on human exposure to bisphenol A (BPA) that food is the predominant BPA exposure source, and that BPA is rapidly and completely cleared from the body. If this is correct, BPA levels in fasting individuals should decrease with increased fasting time.ObjectivesWe set out to investigate the relationship between urine BPA concentration and fasting time in a population-based sample.MethodsWe modeled log BPA urine concentration as a function of fasting time, adjusted for urine creatinine and other confounders, in 1,469 adult participants in the 2003–2004 National Health and Nutrition Examination Survey. We estimated the BPA “population-based half-life” (pop½) for a fasting time of 0–24 hr, < 4.5 hr, 4.5–8.5 hr, and > 8.5 hr.ResultsThe overall pop½ for the 0- to 24-hr interval was 43 hr [95% confidence interval (CI), 26–119 hr]. Among those reporting fasting times of 4.5–8.5 hr (n = 441), BPA declined significantly with fasting time, with a pop½ of 4.1 hr (95% CI, 2.6–10.6 hr). However, within the fasting time intervals of 0–4.5 hr (n = 129) and 8.5–24 hr (n = 899), we saw no appreciable decline. Fasting time did not significantly predict highest (> 12 ng/mL) or lowest (below limit of detection) BPA levels.ConclusionsOverall, BPA levels did not decline rapidly with fasting time in this sample. This suggests substantial nonfood exposure, accumulation in body tissues such as fat, or both. Explaining these findings may require experimental pharmacokinetic studies of chronic BPA exposure, further examination of BPA levels and effects in fat, and a search for important nonfood sources.

Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000 μg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0–24h),we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose–response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-μg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes.

Background: In male rodents, anogenital distance (AGD) provides a sensitive and continuous correlate of androgen exposure in the intrauterine environment and predicts later reproductive success. Some endocrine-disrupting chemicals can alter male reproductive tract development, including shortening AGD, in both rodents and humans. Whether AGD is related to semen quality in human is unknown.Objective: We examined associations between AGD and semen parameters in adult males.Methods: We used multiple regression analyses to model the relationships between sperm parameters and two alternative measures of AGD [from the anus to the posterior base of the scrotum (AGDAS) and to the cephalad insertion of the penis (AGDAP)] in 126 volunteers in Rochester, New York.Results: AGDAS, but not AGDAP, was associated with sperm concentration, motility, morphology, total sperm count, and total motile count (p-values, 0.002–0.048). Men with AGDAS below (vs. above) the median were 7.3 times more likely (95% confidence interval, 2.5–21.6) to have a low sperm concentration (< 20 × 106/mL). For a typical study participant, sperm concentrations were 34.7 × 106/mL and 51.6 × 106/mL at the 25th and 75th percentiles of (adjusted) AGDAS.Conclusions: In our population, AGDAS was a strong correlate of all semen parameters and a predictor of low sperm concentration. In animals, male AGD at birth reflects androgen levels during the masculinization programming window and predicts adult AGD and reproductive function. Our results suggest, therefore, that the androgenic environment during early fetal life exerts a fundamental influence on both AGD and adult sperm counts in humans, as demonstrated in rodents.

Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone’s urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.