Maternal urinary bisphenol a during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study.

BackgroundBisphenol A (BPA) is widely used in the manufacture of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt thyroid function. Although thyroid hormones play a determinant role in human growth and brain development, no studies have investigated relations between BPA exposure and thyroid function in pregnant women or neonates.ObjectiveOur goal was to evaluate whether exposure to BPA during pregnancy is related to thyroid hormone levels in pregnant women and neonates.MethodsWe measured BPA concentration in urine samples collected during the first and second half of pregnancy in 476 women participating in the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We also measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in women during pregnancy, and TSH in neonates.ResultsAssociations between the average of the two BPA measurements and maternal thyroid hormone levels were not statistically significant. Of the two BPA measurements, only the one taken closest in time to the TH measurement was significantly associated with a reduction in total T4 (β = -0.13 µg/dL per log2 unit; 95% CI: -0.25, 0.00). The average of the maternal BPA concentrations was associated with reduced TSH in boys (-9.9% per log2 unit; 95% CI: -15.9%, -3.5%) but not in girls. Among boys, the relation was stronger when BPA was measured in the third trimester of pregnancy and decreased with time between BPA and TH measurements.ConclusionResults suggest that exposure to BPA during pregnancy is related to reduced total T4 in pregnant women and decreased TSH in male neonates. Findings may have implications for fetal and neonatal development

Lessons Learned for the Assessment of Children’s Pesticide Exposure: Critical Sampling and Analytical Issues for Future Studies

In this article we examine sampling strategies and analytical methods used in a series of recent studies of children’s exposure to pesticides that may prove useful in the design and implementation of the National Children’s Study. We focus primarily on the experiences of four of the National Institute of Environmental Health Sciences/U.S. Environmental Protection Agency/ Children’s Centers and include University of Washington studies that predated these centers. These studies have measured maternal exposures, perinatal exposures, infant and toddler exposures, and exposure among young children through biologic monitoring, personal sampling, and environmental monitoring. Biologic monitoring appears to be the best available method for assessment of children’s exposure to pesticides, with some limitations. It is likely that a combination of biomarkers, environmental measurements, and questionnaires will be needed after careful consideration of the specific hypotheses posed by investigators and the limitations of each exposure metric. The value of environmental measurements, such as surface and toy wipes and indoor air or house dust samples, deserves further investigation. Emphasis on personal rather than environmental sampling in conjunction with urine or blood sampling is likely to be most effective at classifying exposure. For infants and young children, ease of urine collection (possible for extended periods of time) may make these samples the best available approach to capturing exposure variability of nonpersistent pesticides; additional validation studies are needed. Saliva measurements of pesticides, if feasible, would overcome the limitations of urinary metabolite-based exposure analysis. Global positioning system technology appears promising in the delineation of children’s time–location patterns

Molecular diversity and population structure at the Cytochrome P450 3A5 gene in Africa.

Cytochrome P450 3A5 (CYP3A5) is an enzyme involved in the metabolism of many therapeutic drugs. CYP3A5 expression levels vary between individuals and populations, and this contributes to adverse clinical outcomes. Variable expression is largely attributed to four alleles, CYP3A5*1 (expresser allele); CYP3A5*3 (rs776746), CYP3A5*6 (rs10264272) and CYP3A5*7 (rs41303343) (low/non-expresser alleles). Little is known about CYP3A5 variability in Africa, a region with considerable genetic diversity. Here we used a multi-disciplinary approach to characterize CYP3A5 variation in geographically and ethnically diverse populations from in and around Africa, and infer the evolutionary processes that have shaped patterns of diversity in this gene. We genotyped 2538 individuals from 36 diverse populations in and around Africa for common low/non-expresser CYP3A5 alleles, and re-sequenced the CYP3A5 gene in five Ethiopian ethnic groups. We estimated the ages of low/non-expresser CYP3A5 alleles using a linked microsatellite and assuming a step-wise mutation model of evolution. Finally, we examined a hypothesis that CYP3A5 is important in salt retention adaptation by performing correlations with ecological data relating to aridity for the present day, 10,000 and 50,000 years ago

Organophosphorous pesticide breakdown products in house dust and children’s urine.

Human exposure to preformed dialkylphosphates (DAPs) in food or the environment may affect the reliability of DAP urinary metabolites as biomarkers of organophosphate (OP) pesticide exposure. We conducted a study to investigate the presence of DAPs in indoor residential environments and their association with children’s urinary DAP levels. We collected dust samples from homes in farmworker and urban communities (40 homes total, n=79 samples) and up to two urine samples from resident children ages 3-6 years. We measured six DAPs in all samples and eight DAP-devolving OP pesticides in a subset of dust samples (n=54). DAPs were detected in dust with diethylphosphate (DEP) being the most frequently detected (>=60%); detection frequencies for other DAPs were 0.05). Detection of DEP, chlorpyrifos, or diazinon, was not associated with DEP and/or DEPþdiethylthiophosphate detection in urine (Kappa coefficients=-0.33 to 0.16). Finally, estimated nondietary ingestion intake from DEP in dust was found to be <=5% of the dose calculated from DEP levels in urine, suggesting that ingestion of dust is not a significant source of DAPs in urine if they are excreted unchanged.This work was supported by EPA (RD 83171001) and NIEHS (PO1 ES009605). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the EPA, NIEHS, or other funders. Additional support was provided by an EPA STAR Doctoral Fellowship (F5D30812), the University of California Institute for Mexico and the United States (UC MEXUS), and the Center for Latino Policy Research at the University of California at Berkeley

Organophosphate Pesticide Exposure and Neurobehavioral Performance in Agricultural and Nonagricultural Hispanic Workers

Our understanding of the health risks of farmworkers exposed to pesticides in their work and home environments is rapidly increasing, although studies designed to examine the possible neurobehavioral effects of low-level chronic pesticide exposure are limited. We measured dialkyl phosphate urinary metabolite levels, collected environmental dust samples from a subset of homes, obtained information on work practices, and conducted neurobehavioral tests on a sample of farmworkers in Oregon. Significant correlations between urinary methyl metabolite levels and total methyl organophosphate (azinphos-methyl, phosmet, malathion) house dust levels were observed. We found the neurobehavioral performance of Hispanic immigrant farmworkers to be lower than that observed in a nonagricultural Hispanic immigrant population, and within the sample of agricultural workers there was a positive correlation between urinary organophosphate metabolite levels and poorer performance on some neurobehavioral tests. These findings add to an increasing body of evidence of the association between low levels of pesticide exposure and deficits in neurobehavioral performance

Epidemiologic Evaluation of Measurement Data in the Presence of Detection Limits

Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of “fill-in” values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5–10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case–control study of non-Hodgkin lymphoma

Association of Housing Disrepair Indicators with Cockroach and Rodent Infestations in a Cohort of Pregnant Latina Women and Their Children

Health burdens associated with poor housing and indoor pest infestations are likely to affect young children in particular, who spend most of their time indoors at home. We completed environmental assessments in 644 homes of pregnant Latina women and their children living in the Salinas Valley, California. High residential densities were common, with 39% of homes housing > 1.5 persons per room. Housing disrepair was also common: 58% of homes had peeling paint, 43% had mold, 25% had water damage, and 11% had rotting wood. Evidence of cockroaches and rodents was present in 60% and 32% of homes, respectively. Compared with representative national survey data from the U.S. Department of Housing and Urban Development, homes in our sample were more likely to have rodents, peeling paint, leaks under sinks, and much higher residential densities. The odds of rodent infestations in homes increased in the presence of peeling paint [odds ratio (OR) 2.1; 95% confidence interval (CI), 1.5–3.1], water damage (OR 1.9; 95% CI, 1.2–2.7), and mold (OR 1.5; 95% CI, 1.0–2.1). The odds of cockroach infestation increased in the presence of peeling paint (OR 3.8; 95% CI, 2.7–5.6), water damage (OR 1.9; 95% CI, 1.2–2.9), or high residential density (OR 2.1; 95% CI, 1.2–3.8). Homes that were less clean than average were more prone to both types of infestations. Pesticides were stored or used in 51% of households, partly to control roach and rodent infestations. These data indicate that adverse housing conditions are common in this community and increase the likelihood of pest infestations and home pesticide use. Interventions to improve housing and promote children’s health and safety in this population are needed

Developmental Changes in PON1 Enzyme Activity in Young Children and Effects of PON1 Polymorphisms

BackgroundParaoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorus pesticides (OPs) and is also involved in oxidative stress pathways.ObjectivesPON1 activity in newborns is lower than in adults, but the ontogeny of PON1 activity is poorly characterized in young children. We examined the effects of age and PON1 genotype on enzyme activity in a birth cohort of Mexican-American children.MethodsWe determined three substrate-specific measures of PON1 activity in 1,143 plasma samples collected longitudinally from 458 children at five time points from birth through 7 years of age, and genotyped PON1 polymorphisms at positions 192 and -108 in these children.ResultsContrary to previous reports that PON1 activities plateau by 2 years of age, we observed an age-dependent increase in all three PON1 measures from birth through 7 years of age (p &lt; 0.0001). The PON1(192) genotype significantly modified the effect of age on paraoxonase (POase) activity (p &lt; 0.0001) such that increases in enzyme activity with age were influenced by the number of R alleles in a dose-dependent manner. Children with the PON1(-108CC192RR) diplotype had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with children with the PON1(-108TT192QQ) diplotype.ConclusionsLower levels of the PON1 enzyme, which is involved in protection against OPs and oxidative stress, persist in young children past 2 years of age through at least 7 years of age. Future policies addressing pesticide exposure in children should take into account that the window of vulnerability to OPs in young children may last beyond infancy