Association of urinary phenols with increased body weight measures and obesity in children and adolescents.

OBJECTIVE: To examine the association of urinary levels of the environmental phenol pesticides 2,5-dichlorophenol, 2,4-dichlorophenol, and triclosan with body weight outcomes in children and adolescent participants in the National Health and Nutrition Examination Survey 2007-2010. STUDY DESIGN: We performed multivariate linear and multinomial logistic regressions to analyze the association of body mass index (BMI) z-score, waist circumference (WC), and obesity with urinary pesticide concentration in children and adolescents. RESULTS: After adjustment for covariates, we found a statistically significant positive association (P < .05) between both 2,5-dichlorophenol and 2,4-dichlorophenol with BMI z-score, WC, and obesity in children and adolescents. After stratification by age, the significant associations remained only in adolescents (ages 12-19). No associations were found between triclosan and any of the body weight outcomes. CONCLUSIONS: We found an association between dichlorophenols and increased body weight measures (BMI z-score, WC, and obesity) in adolescents. However, further studies, such as a longitudinal study, are needed to confirm and elucidate on our findings.

DDT/DDE and breast cancer: a meta-analysis.

The biological basis for investigating dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk stems from in vitro and animal studies indicating that DDT has estrogenic properties. The objective of this study was to update a meta-analysis from 2004 which found no association between dichlorodiphenyldichloroethylene (DDE) and breast cancer. We searched PubMed and Web of Science for studies published through June 2012 assessing DDT/DDE exposure and breast cancer. Summary Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated for the prevalence of breast cancer in the highest versus the lowest exposed groups for DDT and DDE. Difference of means of exposure for cases versus controls was analyzed for DDT and DDE. From the 500 studies screened, 46 were included in the meta-analysis. Slightly elevated, but not statistically significant summary ORs were found for DDE (1.05; 95% CI: 0.93-1.18) and DDT (1.02; 95% CI: 0.92-1.13). Lipid adjusted difference of means analysis found a significantly higher DDE concentration in cases versus controls (11.30 ng/g lipid; p=0.01). No other difference of means analysis found significant relationships. The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans.

Association of low-level blood lead and blood pressure in NHANES 1999-2006.

This study investigated whether low blood-lead levels (≤10 µg/dL) were associated with blood pressure (BP) outcomes. The authors analyzed data from National Health and Nutrition Examination Survey 1999-2006 and participants aged 20 years or older. Outcome variables were systolic and diastolic BP measurements, pulse pressure, and hypertension status. Multivariable linear and logistic regressions stratified by race/ethnicity and gender were performed. Blood lead levels (BLL) were significantly correlated with higher systolic BP among black men and women, but not white or Mexican-American participants. BLLs were significantly associated with higher diastolic BPs among white men and women and black men, whereas, a negative association was observed in Mexican-American men that had, also, a wider pulse pressure. Black men in the 90th percentile of blood lead distribution (BLL≥3.50 µg/dL) compared to black men in the 10th percentile of blood lead distribution (BLL≤0.7 µg/dL) had a significant increase of risk of having hypertension (adjusted POR=2.69; 95% CI: 1.08-6.72). In addition, blood cadmium was significantly associated with hypertension and systolic and diastolic blood. This study found that, despite the continuous decline in blood lead in the U.S. population, lead exposure disparities among race and gender still exist.

Perfluoroalkyl acids, hyperuricemia and gout in adults: Analyses of NHANES 2009-2014.

BACKGROUND: Previous studies have reported a positive association of perfluoralkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), with hyperuricemia. The objective of the study is to investigate whether there is an association between concurrent serum levels of several PFAAs and gout, serum uric acid (SUA) or hyperuricemia in the U.S. adult population as represented by the National Health and Nutrition Examination Survey (NHANES) 2009-2014 sample (n = 4917). The PFAAs investigated include PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS) and PFOS. METHODS: This cross-sectional study used multivariate logistic regressions to analyze the association of single PFAAs with hyperuricemia and self-reported gout; the association with SUA was analyzed by multivariate linear regression. Analyses were adjusted for race/ethnicity, age, sex, education, alcohol consumption, smoking, serum cotinine, BMI, diabetes, hypertension, chronic kidney disease, and SUA (for gout only). RESULTS: Higher quartile values of serum PFOA and PFHxS were associated with increased odds of self-reported gout. There was a positive association of SUA with increased levels of PFOA, PFNA, PFOS, PFHxS and PFDA. Higher quartile values of PFOA, PFNA, and PFHxS were associated with higher odds of hyperuricemia. CONCLUSIONS: In this population-based cross-sectional analysis, we found an association between selected PFAAs and self-reported gout. We also confirmed previous reports of an association between several PFAAs and hyperuricemia. Our study suggests that exposure to PFAAs may be a risk factor for hyperuricemia and gout.

Lead and delta-aminolevulinic acid dehydratase polymorphism: where does it lead? A meta-analysis.

BACKGROUND: Lead poisoning affects many organs in the body. Lead inhibits delta-aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1 and ALAD2. OBJECTIVE: Our meta-analysis studied the effects of the ALAD polymorphism on a) blood and bone lead levels and b) indicators of target organ toxicity. DATA SOURCE: We included studies reporting one or more of the following by individuals with genotypes ALAD1-1 and ALAD1-2/2-2: blood lead level (BLL), tibia or trabecular lead level, zinc protoporphyrin (ZPP), hemoglobin, serum creatinine, blood urea nitrogen (BUN), dimercaptosuccinic acid-chelatable lead, or blood pressure. DATA EXTRACTION: Sample sizes, means, and standard deviations were extracted for the genotype groups. DATA SYNTHESIS: There was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 microg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 microg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes. CONCLUSION: Carriers of the ALAD2 allele had higher BLLs than those who were ALAD1 homozygous and higher hemoglobin and lower ZPP, and the latter seems to be inversely related to BLL. Effects on other organs were not well delineated, partly because of the small number of subjects studied and potential modifications caused by other proteins in target tissues or by other polymorphic genes.

Genetic factors that might lead to different responses in individuals exposed to perchlorate.

Perchlorate has been detected in groundwater in many parts of the United States, and recent detection in vegetable and dairy food products indicates that contamination by perchlorate is more widespread than previously thought. Perchlorate is a competitive inhibitor of the sodium iodide symporter, the thyroid cell-surface protein responsible for transporting iodide from the plasma into the thyroid. An estimated 4.3% of the U.S. population is subclinically hypothyroid, and 6.9% of pregnant women may have low iodine intake. Congenital hypothyroidism affects 1 in 3,000 to 1 in 4,000 infants, and 15% of these cases have been attributed to genetic defects. Our objective in this review is to identify genetic biomarkers that would help define subpopulations sensitive to environmental perchlorate exposure. We review the literature to identify genetic defects involved in the iodination process of the thyroid hormone synthesis, particularly defects in iodide transport from circulation into the thyroid cell, defects in iodide transport from the thyroid cell to the follicular lumen (Pendred syndrome), and defects of iodide organification. Furthermore, we summarize relevant studies of perchlorate in humans. Because of perchlorate inhibition of iodide uptake, it is biologically plausible that chronic ingestion of perchlorate through contaminated sources may cause some degree of iodine discharge in populations that are genetically susceptible to defects in the iodination process of the thyroid hormone synthesis, thus deteriorating their conditions. We conclude that future studies linking human disease and environmental perchlorate exposure should consider the genetic makeup of the participants, actual perchlorate exposure levels, and individual iodine intake/excretion levels.

Age and sex differences in childhood and adulthood obesity association with phthalates: analyses of NHANES 2007-2010.

BACKGROUND: Exposure to environmental chemicals may play a role in the development of obesity. Evidence suggests phthalate exposure may be associated with obesity in children and adults. OBJECTIVE: To examine the association of ten urinary phthalate metabolites mono-n-butyl phthalate (MnBP), mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-2-ethylhexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(carboxylnonyl) phthalate (MCNP), and mono-(carboxyoctyl) phthalate (MCOP) grouped by molecular weight of their parent compounds with body weight outcomes in children, adolescent and adult participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2010. METHODS: We performed multinomial logistic regression to analyze the association between obesity and urinary phthalate metabolite concentrations in children and adolescents and adults. RESULTS: Low molecular weight (LMW) phthalate metabolites (MnBP, MEP and MiBP) are significantly (p<0.05) associated with higher odds for obesity in male children and adolescents. High molecular weight (HMW) phthalate metabolites (MECPP, MEHHP, MEOHP, MEHP, MBzP, MCNP, and MCOP) and di-2-ethylhexyl phthalate (DEHP) metabolites (MEHHP, MEOHP, MEHP and MECPP) are significantly (p<0.05) associated with higher OR for obesity in all adults. Additionally, DEHP metabolites are significantly associated with obesity in all female adults; whereas DEHP and HMW metabolites are significantly associated with OR for obesity in males 60 years and older. CONCLUSIONS: We found age and sex differences in the association between urinary phthalate metabolite concentrations and body weight outcomes. Reverse causation cannot be excluded since overweight and obese people will have more fat mass, they may store more phthalates, thus leading to higher excretion concentrations.

Sodium and potassium in health and disease.

Sodium and potassium are essential for human health. They are important ions in the body and are associated with many physiologic and pathophysiologic processes. The chapter summarizes the basic physiologic actions of sodium and potassium on membranes of the neurologic and muscular systems. It provides information regarding the kinetics, i.e., absorption, distribution, and excretion of these ions and their movement between the intracellular and extracellular compartments. It also explains the physiologic systems that can influence proper homeostasis between sodium and potassium. Concentrations of sodium in the blood that exceed or do not reach the normal value range are called hypernatremia or hyponatremia, respectively. Similarly, the clinicians recognize hyperkalemia and hypokalemia. Pathologies associated with these states are described and examples of some of the diseases are presented here.

Pendrin mediates uptake of perchlorate in a mammalian in vitro system.

Perchlorate is a known endocrine disruptor present in groundwater, vegetables and dairy food products in many regions of the United States. It interferes with the uptake of iodide into the thyrocyte by the sodium-iodide symporter at the basolateral surface, thus potentially disrupting the synthesis of thyroid hormone. Because transport of iodide from the thyroid follicular cells to the follicular lumen is mediated by the protein pendrin at the apical surface, we hypothesized that perchlorate may also interact with this protein. Therefore, HeLa cells were transfected with the human SLC26A4 gene, which encodes pendrin, to generate an in vitro mammalian system expressing the recombinant pendrin protein (HeLa-PDS). The HeLa-PDS cells, along with untransfected cells, were then cultured in presence of iodide and/or perchlorate. Intracellular levels of these two chemicals were measured by ion chromatography tandem mass spectrometry. Results from this study show that iodide and perchlorate uptake increases significantly in HeLa-PDS cells as compared to untransfected cells. Thus, recombinant HeLa cells expressing pendrin protein accumulate iodide and perchlorate intracellularly, indicating that pendrin is involved in the uptake of perchlorate. Additional results from this study suggest that iodide and perchlorate competitively inhibit each other for uptake by pendrin. The ability of perchlorate to compete with iodide for uptake by both basal and apical transporters may increase the potential of perturbation of thyroid homeostasis and therefore the estimated risk posed to susceptible human populations.

Organic mercury compounds: human exposure and its relevance to public health.

Humans may be exposed to organic forms of mercury by either inhalation, oral, or dermal routes, and the effects of such exposure depend upon both the type of mercury to which exposed and the magnitude of the exposure. In general, the effects of exposure to organic mercury are primarily neurologic, while a host of other organ systems may also be involved, including gastrointestinal, respiratory, hepatic, immune, dermal, and renal. While the primary source of exposure to organic mercury for most populations is the consumption of methylmercury-contaminated fish and shellfish, there are a number of other organomercurials to which humans might be exposed. The antibacterial and antifungal properties of organomercurials have resulted in their long use as topical disinfectants (thimerosal and merbromin) and preservatives in medical preparations (thimerosal) and grain products (both methyl and ethyl mercurials). Phenylmercury has been used in the past in paints, and dialkyl mercurials are still used in some industrial processes and in the calibration of certain analytical laboratory equipment. The effects of exposure to different organic mercurials by different routes of exposure are summarized in this article.