Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-29 (of 29 Records) |
Query Trace: Whyatt J[original query] |
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Prenatal exposure to organophosphate and pyrethroid insecticides and the herbicide 2,4-dichlorophenoxyacetic acid and size at birth in urban pregnant women
Balalian AA , Liu X , Herbstman JB , Daniel S , Whyatt R , Rauh V , Calafat AM , Wapner R , Factor-Litvak P . Environ Res 2021 201 111539 BACKGROUND: Organophosphate insecticides and the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) are used to protect crops or control weeds. Pyrethroids are used to manage pests both in agriculture and in residences, and to reduce the transmission of insect-borne diseases. Several studies have reported inverse associations between exposure to organophosphates (as a larger class) and birth outcomes but these associations have not been conclusive for pyrethroids or 2,4-D, specifically. We aimed to investigate the association between birth outcomes and urinary biomarkers of pyrethroids, organophosphates and 2,4-D among healthy pregnant women living in New York City. METHODS: We quantified urinary biomarkers of 2,4-D and of organophosphate and pyrethroid insecticides from 269 women from two cohorts: a) Thyroid Disruption And Infant Development (TDID) and b) Sibling/Hermanos cohort (S/H). We used weighted quantile sum regression and multivariable linear regression models to evaluate the associations between a mixture of urinary creatinine-adjusted biomarker concentrations and birth outcomes of length, birthweight and head circumference, controlling for covariates. We also used linear regression models and further classified biomarkers concentrations into three categories (i: non-detectable; ii: between the limit of detection and median; and iii: above the median) to investigate single pesticides' association with these birth outcomes. Covariates considered were delivery mode, ethnicity, marital status, education, income, employment status, gestational age, maternal age and pre-pregnancy BMI. Analyses were conducted separately for each cohort and stratified by child sex within each cohort. RESULTS: In TDID cohort, we found a significant inverse association between weighted quantile sum of mixture of pesticides and head circumference among boys. We found that the urinary biomarkers of organophosphate chlorpyrifos, TCPy, and 2,4-D had the largest contribution to the overall mixture effect in the TDID cohort among boys (b = -0.57, 95%CI: -0.92, -0.22) (weights = 0.81 and 0.16 respectively) but not among girls. In the multivariable linear regression models, we found that among boys, for each log unit increase in 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of organophosphate chlorpyrifos) in maternal urine, there was a -0.56 cm decrease in head circumference (95%CI: -0.92, -0.19). Among boys in the TDID cohort, 2,4-D was associated with smaller head circumference in the second (b = -1.57; 95%CI: -2.74, -0.39) and third (b = -1.74, 95%CI: -2.98, -0.49) concentration categories compared to the first. No associations between pyrethroid and organophosphate biomarkers and birth outcomes were observed in girls analyzed in WQS regression or individually in linear regression models in TDID cohort. In the S/H cohort, head circumference increased with higher concentrations of 3-phenoxybenzoic acid (3-PBA, a biomarker of several pyrethroids) (b = 0.53, 95%CI: 0.03, 1.04) among boys and head circumference was lower among girls in the high compared to low category of 2,4-D (b = -2.27, 95%CI: - 3.98, -0.56). Birth length was also positively associated with the highest concentration of 2,4-D compared to the lowest among boys (b = 4.01, 95%CI: 0.02,8.00). CONCLUSIONS: Weighted quantile sum of pesticides was negatively associated with head circumference among boys in one cohort. Nonetheless, due to directional homogeneity assumption in WQS no positive associations were detected. In linear regression models with individual pesticides, concentrations of TCPy were inversely associated with head circumference in boys and higher concentrations of 2,4-D was inversely associated with head circumference among girls; 2,4-D concentrations were also associated with higher birth length among boys. Concentrations of 3-PBA was positively associated with head circumference among boys. |
Prenatal and early childhood exposure to phthalates and childhood behavior at age 7 years
Daniel S , Balalian AA , Insel BJ , Liu X , Whyatt RM , Calafat AM , Rauh VA , Perera FP , Hoepner LA , Herbstman J , Factor-Litvak P . Environ Int 2020 143 105894 BACKGROUND: Emerging evidence suggests that phthalate exposure may be associated with behavior problems in children and that these associations may be sex specific. METHODS: In a follow up study of 411 inner-city minority mothers and their children, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monethyl phthalate (MEP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in maternal urine samples collected during the third trimester and in child urine samples at ages 3 and 5 years. The Conners' Parent Rating Scale-Revised: Long Form (CPRS) and Child Behavior Checklist (CBCL) were administered to the mothers to assess children's behavior problems at 7 years of age. The analysis included children with available measures of CBCL, CPRS and phthalates measured in maternal urine. We performed both Quasi-Poisson regression and a mixture analysis using Weighted Quantile Sum(WQS) regression to assess the risk for CPRS scores and for internalizing and externalizing behaviors (from the CBCL) following intra-uterine exposure to the phthalate metabolites for boys and girls separately. RESULTS: Among boys, increases in in anxious-shy behaviors were associated with prenatal exposure to MBzP (Mean Ratio [MR] = 1.20, 95%CI 1.05-1.36) and MiBP (Mean Ratio (MR) = 1.22, 95%CI 1.02-1.47). Among girls, increases in perfectionism were associated with MBzP (MR = 1.15, 95%CI 1.01-1.30). In both boys and girls, increases in psychosomatic problems were associated with MiBP (MR = 1.28, 95%CI 1.02-1.60), and MnBP (MR = 1.28, 95%CI 1.02-1.59), respectively. Among girls, decreased hyperactivity was associated with two DEHP metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MR = 0.83, 95%CI 0.71-0.98) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MR = 0.85, 95%CI 0.72-0.99). Using weighted Quantile Sum logistic regression, no associations were found between the Weighted Quantile Sum (WQS) of phthalate metabolites and CPRS scores or externalizing and internalizing behaviors. Nonetheless, when the analysis was performed separately for DEHP and non-DEHP metabolites significant associations were found between the WQS of DEHP metabolites and social problems in boys (OR = 2.15, 95%CI 1.13-4.06, p-value = 0.02) anxious-shy problems in girls (OR = 2.19, 95%CI 1.15-4.16, p = 0.02), and emotional lability problems in all children (OR = 0.61, 95%CI 0.38-0.97, p = 0.04). MEHP and MEOHP were the most highly weighted DEHP metabolites in WQS mixture. The analysis performed with CBCL scale corroborated these associations. CONCLUSION: Concentration of non-DEHP metabolites was associated with anxious-shy behaviors among boys. DEHP phthalate metabolites were associated with decreased hyperactivity and impulsivity among girls on CPRS scores. These findings lend further support to the adverse associations between prenatal phthalate exposure and childhood outcomes, and clearly suggest that such associations are sex and mixture specific. |
Functional connectivity of the reading network is associated with prenatal polybrominated diphenyl ether concentrations in a community sample of 5 year-old children: A preliminary study
Margolis AE , Banker S , Pagliaccio D , De Water E , Curtin P , Bonilla A , Herbstman JB , Whyatt R , Bansal R , Sjodin A , Milham MP , Peterson BS , Factor-Litvak P , Horton MK . Environ Int 2019 134 105212 Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N=33). Maternal serum PBDE concentrations ( summation operatorPBDE) were measured at 12.2+/-2.8weeks gestation (mean+/-SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between summation operatorPBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher summation operatorPBDE showed reduced GE of the RN; summation operatorPBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, summation operatorPBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between summation operatorPBDE concentrations and reading problems observed previously in older children. |
Pre and postnatal polybrominated diphenyl ether concentrations in relation to thyroid parameters measured during early childhood
Cowell W , Sjodin A , Jones RL , Wang Y , Wang S , Whyatt R , Factor-Litvak P , Bradwin G , Hassoun A , Oberfield S , Herbstman J . Thyroid 2019 29 (5) 631-641 BACKGROUND: Penta brominated diphenyl ethers (PentaBDEs) are endocrine disrupting chemicals that structurally resemble thyroid hormones and were widely used as flame retardants in household consumer products from 1975-2004. Polybrominated diphenyl ethers (PBDEs) cross the placenta and evidence suggests that for many children, body burdens may peak during toddler years. We aimed to understand the impact of exposure timing by examining both pre and postnatal exposure to BDE-47, the predominant PentaBDE congener detected in humans, in relation to thyroid hormone parameters measured during early childhood. METHODS: The Columbia Center for Children's Environmental Health Mothers and Newborns Study is a prospective birth cohort of African American and Dominican maternal-child pairs. Pregnant women were recruited from two prenatal clinics in Northern Manhattan and the South Bronx between 1998 and 2006. Participants included 158 children with 1) plasma PBDE concentrations measured at birth and toddler years (age 2-3), and 2) serum thyroid parameters measured at 3 and/or 5 years. Outcomes included concentrations of serum thyroid stimulating hormone (TSH), free thyroxine (fT4) and total thyroxine (T4). RESULTS: Children with high exposure to BDE-47 during the prenatal period (-17%, 95% CI -29, -2) or toddler age (-19%, 95% CI: -31, -5) had significantly lower geometric mean TSH levels compared to children with low BDE-47 exposure throughout early life. Associations with T4 were also inverse, however, they did not reach statistical significance at the p=0.05 level. Sex-stratified models suggest associations with postnatal exposure may be stronger among boys compared to girls. CONCLUSIONS: The thyroid regulatory system may be sensitive to BDE-47 during prenatal and postnatal periods. |
A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood
de Water E , Curtin P , Zilverstand A , Sjodin A , Bonilla A , Herbstman JB , Ramirez J , Margolis AE , Bansal R , Whyatt RM , Peterson BS , Factor-Litvak P , Horton MK . J Child Psychol Psychiatry 2019 60 (9) 1010-1020 BACKGROUND: The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood. METHODS: In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph-theoretical approach) in 5-year-old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems. RESULTS: Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (beta's = .01, FDR-corrected p's </= .05); (b) more reported EF problems (beta's = .001, FDR-corrected p's </= .05). Higher global efficiency of brain areas involved in visual attention was associated with more EF problems (beta's = .01, FDR-corrected p's < .05). CONCLUSIONS: Intrinsic functional network organization of visual attention brain areas linked prenatal PBDE concentrations to EF problems in childhood. Visual attention may contribute to the development of higher-order cognitive functions, such as EF, which could be explored in future studies. |
Phthalates and thyroid function in preschool age children: Sex specific associations
Morgenstern R , Whyatt RM , Insel BJ , Calafat AM , Liu X , Rauh VA , Herbstman J , Bradwin G , Factor-Litvak P . Environ Int 2017 106 11-18 BACKGROUND: Research relating either prenatal or concurrent measures of phthalate exposure to thyroid function in preschool children is inconclusive. METHODS: In a study of inner-city mothers and their children, metabolites of di-n-butyl phthalate, butylbenzyl phthalate, di-isobutyl phthalate, di(2-ethylhexyl) phthalate, and diethyl phthalate were measured in a spot urine sample collected from women in late pregnancy and from their children at age 3years. We measured children's serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) at age 3. Linear regression models were used to investigate the associations between phthalate metabolites, measured in maternal urine during late pregnancy and measured in child urine at age 3 and thyroid function measured at age 3. RESULTS: Mean concentrations (ranges) were 1.42ng/dL (1.02-2.24) for FT4, and 2.62uIU/mL (0.61-11.67) for TSH. In the children at age 3, among girls, FT4 decreased with increasing loge mono-n-butyl phthalate [estimated b=-0.06; 95% CI: (-0.09, -0.02)], loge mono-isobutyl phthalate [b=-0.05; 95% CI: (-0.09, -0.01)], loge monoethyl phthalate [b=-0.04; 95% CI: (-0.07, -0.01)], and loge mono(2-ethyl-5-hydroxyhexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.003)] and loge mono(2-ethyl-5-oxy-hexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.004)]. In contrast, among boys, we observed no associations between FT4 and child phthalate metabolites at age 3. On the other hand, in late gestation, FT4 increased with increasing loge mono-(2-ethylhexyl) phthalate [estimated b=0.04; 95% CI: (0.02, 0.06)] and no sex difference was observed. We found no associations between phthalate biomarkers measured in either the child or prenatal samples and TSH at age 3. CONCLUSIONS: The data show inverse and sex specific associations between specific phthalate metabolites measured in children at age 3 and thyroid function in preschool children. These results may provide evidence for the hypothesis that reductions in thyroid hormones mediate associations between early life phthalate exposure and child cognitive outcomes. |
Urinary concentrations of insecticide and herbicide metabolites among pregnant women in rural Ghana: A pilot study
Wylie BJ , Ae-Ngibise KA , Boamah EA , Mujtaba M , Messerlian C , Hauser R , Coull B , Calafat AM , Jack D , Kinney PL , Whyatt R , Owusu-Agyei S , Asante KP . Int J Environ Res Public Health 2017 14 (4) Use of pesticides by households in rural Ghana is common for residential pest control, agricultural use, and for the reduction of vectors carrying disease. However, few data are available about exposure to pesticides among this population. Our objective was to quantify urinary concentrations of metabolites of organophosphate (OP), pyrethroid, and select herbicides during pregnancy, and to explore exposure determinants. In 2014, 17 pregnant women from rural Ghana were surveyed about household pesticide use and provided weekly first morning urine voids during three visits (n = 51 samples). A total of 90.1% (46/51) of samples had detectable OP metabolites [geometric mean, GM (95% CI): 3,5,6-trichloro-2-pyridinol 0.54 microg/L (0.36-0.81), para-nitrophenol 0.71 microg/L (0.51-1.00)], 75.5% (37/49) had detectable pyrethroid metabolites [GM: 3-phenoxybenzoic acid 0.23 microg/L (0.17, 0.32)], and 70.5% (36/51) had detectable 2,4-dichlorophenoxyacetic acid levels, a herbicide [GM: 0.46 microg/L (0.29-0.73)]. Concentrations of para-nitrophenol and 2,4-dichlorophenoxyacetic acid in Ghanaian pregnant women appear higher when compared to nonpregnant reproductive-aged women in a reference U.S. POPULATION: Larger studies are necessary to more fully explore predictors of exposure in this population. |
Maternal prenatal urinary phthalate metabolite concentrations and visual recognition memory among infants at 27 weeks
Ipapo KN , Factor-Litvak P , Whyatt RM , Calafat AM , Diaz D , Perera F , Rauh V , Herbstman JB . Environ Res 2017 155 7-14 BACKGROUND: Prior research has demonstrated inverse associations between maternal prenatal urinary phthalate metabolite concentrations and cognitive development assessed in preschool and school-aged children. While there are a limited number of studies that evaluated these associations during infancy, no study has evaluated whether these associations exist when using the Fagan Test of Infant Intelligence (FTII), which captures novelty preference as a function of visual recognition memory. OBJECTIVE: We evaluated associations between phthalate metabolite concentrations in maternal prenatal urine and cognition in infancy using the FTII at 27 weeks and determine if these associations are sex-specific. METHODS: Mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), mono-ethyl phthalate (MEP), mono-3-carboxypropyl phthalate (MCPP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in urine samples collected from 168 minority women living in urban neighborhoods during their third trimester of pregnancy. The FTII was administered to infants at 27 weeks to measure visual recognition memory and was recorded as the novelty preference score. RESULTS: There were no associations between prenatal phthalate metabolite concentrations and novelty preference score in the full sample. However, there was evidence of effect modification by infant sex. Sex-stratified models demonstrated that compared to girls in the lowest tertile of MBzP concentrations, girls in tertiles 2 and 3 had, on average, 3.98 and 4.65 points lower novelty preference scores (p-value=0.04 and 0.03, respectively). The relationship was similar for SigmaDEHP, MiBP, and MEP. Effects among boys were inconsistent and generally not significant. CONCLUSION: Maternal prenatal exposure to some phthalates was negatively associated with visual recognition memory as measured by the FTII among girls at age 27 weeks. |
Response to "Comment on 'Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology'"
Calafat AM , Longnecker MP , Koch HM , Swan SH , Hauser R , Goldman LR , Lanphear BP , Rudel RA , Engel SM , Teitelbaum SL , Whyatt RM , Wolff MS . Environ Health Perspect 2016 124 (4) A66-7 We appreciate the opportunity to respond to the letter from Stahlhut et al. regarding our Brief Communication. We stressed the importance of biospecimen integrity and the potential danger of unrecognized contamination of convenience samples, particularly with ubiquitous environmental chemicals such as bisphenol A (BPA) and phthalates. | | We did not discuss the important area of experimental research and specifically pharmacokinetic studies, although we based our argument partly on knowledge of concentration changes in various compartments postexposure. We agree that information from pharmacokinetic models is quite valuable and note that experimental studies that use isotope-labeled materials are not susceptible to extraneous contamination. Such experimental studies do not support using polar metabolites, such as unmetabolized BPA, as biomarkers in epidemiologic studies (Thayer et al. 2015). For example, even in situations that may result in exposures higher than background levels, such as handling cash register receipts, BPA serum concentrations are below or near the detection limit and much lower than urinary concentrations (Thayer et al. 2016). |
Bisphenol A and adiposity in an inner-city birth cohort
Hoepner LA , Whyatt RM , Widen EM , Hassoun A , Oberfield SE , Mueller NT , Diaz D , Calafat AM , Perera FP , Rundle AG . Environ Health Perspect 2016 124 (10) 1644-1650 BACKGROUND: Early life exposure to the endocrine disruptor bisphenol A (BPA) may contribute to development of obesity. Prospective evidence in humans on this topic is limited. OBJECTIVES: We examined prenatal and early childhood BPA exposures in relation to childhood measures of adiposity in the Columbia Center for Children's Environmental Health (CCCEH) New York City birth cohort. METHODS: BPA concentrations were measured in prenatal (n=375) and child ages 3 (n=408) and 5 years (n=518) spot urine samples. Childhood anthropometric and bioelectrical impedance outcomes included body mass index z-scores (BMIZ) at 5 and 7 years, and fat mass index (FMI), percent body fat (%BF), and waist circumference (WC) at 7 years. Associations were evaluated using multiple linear regression with continuous and tertile BPA concentrations. RESULTS: Prenatal urinary BPA concentrations were positively associated with child age 7 FMI (beta=0.31 kg/m2, p-value=0.04, [95%CI 0.01, 0.60]), %BF (beta=0.79, p-value=0.04, [95%CI 0.03, 1.55]), and WC (beta=1.29 cm, p-value=0.01, [95%CI 0.29, 2.30]), but not BMIZ, or change in BMIZ between ages 5 and 7 years (all p-values > 0.1). FMI results were sex-specific. Child urinary BPA concentrations were not associated with child anthropometric outcomes (all p-values > 0.05). CONCLUSIONS: Analyses of the CCCEH longitudinal birth cohort found associations between prenatal urinary BPA concentrations and FMI, %BF and WC. Our results suggest that prenatal BPA exposure may contribute to developmental origins of adiposity. These findings are consistent with several prior studies, raising concern about the pervasiveness of BPA. |
Prenatal Exposure to Phthalates and Childhood Body Size in an Urban Cohort
Maresca MM , Hoepner LA , Hassoun A , Oberfield SE , Mooney SJ , Calafat AM , Ramirez J , Freyer G , Perera FP , Whyatt RM , Rundle AG . Environ Health Perspect 2016 124 (4) 514-20 BACKGROUND: Phthalate exposures are hypothesized to increase obesity; however, prior research has been largely cross-sectional. OBJECTIVE: We evaluated associations between prenatal phthalate exposures and body mass index (BMI) at child ages 5 and 7 years. METHODS: Nine metabolites of six phthalates-di(2-ethylhexyl) phthalate (DEHP), di-n-octyl-, di-iso-butyl-, di-n-butyl-, butylbenzyl-, and diethyl phthalates-were measured in spot urine samples collected from pregnant African-American and Dominican women during their third trimester, and from their children at ages 3 and 5 years. To reduce multiple comparison issues, we initially used principal component analysis (PCA) to identify major patterns of natural log (ln)-transformed metabolite concentrations. Height and weight were assessed at ages 5 and 7 years, and fat mass and waist circumference at age 7. Linearized generalized estimating equation analyses related maternal component scores to child anthropometric outcomes at ages 5 (n = 326) and 7 (n = 330) years. RESULTS: PCA identified a DEHP component and a non-DEHP component. In boys, higher maternal non-DEHP, but not DEHP, component scores were associated with lower BMI z-score (beta = -0.30; 95% CI: -0.50, -0.10, n = 156), lower fat percentage (beta = -1.62; 95% CI: -2.91, -0.34, n = 142), and smaller waist circumference (beta = -2.02; 95% CI: -3.71, -0.32, n = 124). No significant associations with anthropometric outcomes were seen in girls (for BMI z-score, beta = 0.07; 95% CI: -0.18, 0.31, n = 181). Interactions between sex and non-DEHP component association with outcomes were statistically significant (p < 0.01). CONCLUSIONS: Contrary to hypotheses, prenatal non-DEHP phthalate exposures were associated with lower BMI z-score, waist circumference, and fat mass in boys during early childhood. |
Prenatal phthalate exposures and body mass index among 4 to 7 year old children: a pooled analysis
Buckley JP , Engel SM , Braun JM , Whyatt RM , Daniels JL , Mendez MA , Richardson DB , Xu Y , Calafat AM , Wolff MS , Lanphear BP , Herring AH , Rundle AG . Epidemiology 2016 27 (3) 449-58 BACKGROUND: Phthalates are hypothesized to cause obesity, but few studies have assessed whether prenatal phthalate exposures are related to childhood body mass index (BMI). METHODS: We included 707 children from three prospective cohort studies enrolled in the United States between 1998 and 2006 who had maternal urinary phthalate metabolite concentrations measured during pregnancy, and measures of weight and height at ages 4 to 7 years. We calculated age- and sex-standardized BMI z-scores and classified children with BMI percentiles ≥85 as overweight/obese. We used mixed effects regression models to estimate associations between a 1-standard deviation increase in natural log phthalate metabolite concentrations and BMI zscores and overweight/obesity. We estimated associations in multiple metabolite models adjusted for confounders, and evaluated heterogeneity of associations by child's sex, race/ethnicity, and cohort RESULTS: Mono-3-carboxypropyl phthalate (MCPP) concentrations were positively associated with overweight/obese status in children (odds ratio [95% credible interval] = 2.1 [1.2, 4.0]) but not with BMI z-scores (beta = -0.02 [-0.15, 0.11]). We did not observe evidence of obesogenic effects for other metabolites. However, monoethyl phthalate (MEP) and summed di-(2-ethylhexyl) phthalate metabolites ( summation operatorDEHP) concentrations were inversely associated with BMI z-scores among girls (MEP beta = -0.14 [-0.28, 0.00]; summation operatorDEHP beta = -0.12 [-0.27, 0.02]). CONCLUSIONS: Maternal urinary MCPP, a non-specific metabolite of several phthalates, was positively associated with childhood overweight/obesity. Metabolites of diethyl phthalate and DEHP were associated with lower BMI in girls but not boys, suggesting prenatal exposures may have sexually dimorphic effects on physical development. |
Co-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women
Horton MK , Blount BC , Valentin-Blasini L , Wapner R , Whyatt R , Gennings C , Factor-Litvak P . Environ Res 2015 143 1-9 BACKGROUND: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy OBJECTIVES: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. METHODS: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (+/-2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. RESULTS: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4-0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. CONCLUSIONS: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. |
Optimal exposure biomarkers for nonpersistent chemicals in environmental epidemiology
Calafat AM , Longnecker MP , Koch HM , Swan SH , Hauser R , Goldman LR , Lanphear BP , Rudel RA , Engel SM , Teitelbaum SL , Whyatt RM , Wolff MS . Environ Health Perspect 2015 123 (7) A166-8 We discuss considerations that are essential when evaluating exposure to nonpersistent, semivolatile environmental chemicals such as phthalates and phenols (e.g., bisphenol A). A biomarker should be chosen to best represent usual personal exposures and not recent, adventitious, or extraneous exposures. Biomarkers should be selected to minimize contamination arising from collection, sampling, or analysis procedures. Pharmacokinetics should be considered; for example, nonpersistent, semivolatile chemicals are metabolized quickly, and urine is the compartment with the highest concentrations of metabolites. Because these chemicals are nonpersistent, knowledge of intraindividual reliability over the biologic window of interest is also required. In recent years researchers have increasingly used blood as a matrix for characterizing exposure to nonpersistent chemicals. However, the biologic and technical factors noted above strongly support urine as the optimal matrix for measuring nonpersistent, semivolatile, hydrophilic environmental agents. |
Vinyl flooring in the home is associated with children's airborne butylbenzyl phthalate and urinary metabolite concentrations
Just AC , Miller RL , Perzanowski MS , Rundle AG , Chen Q , Jung KH , Hoepner L , Camann DE , Calafat AM , Perera FP , Whyatt RM . J Expo Sci Environ Epidemiol 2015 25 (6) 574-9 Prior studies have shown that vinyl flooring as well as the vinyl-softening plasticizers butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) are associated with asthma and airway inflammation. Although DEHP exposure is primarily dietary, whether home vinyl flooring contributes to indoor air and urinary metabolite concentrations for these two phthalates is unclear. Exposures to BBzP and DEHP were examined in a prospective birth cohort of New York City children (n=239) using: (i) visual observation of potential phthalate containing flooring, (ii) a 2-week home indoor air sample, and (iii) concurrent urinary metabolites in a subset (n=193). The category "vinyl or linoleum" flooring was observed in 135 (56%) of monitored rooms; these rooms had statistically significantly higher indoor air geometric mean concentrations of BBzP (23.9 ng/m3) than rooms with wood or carpet flooring (10.6 ng/m3). Children from homes with "vinyl or linoleum" flooring also had significantly higher urinary BBzP metabolite concentrations than other children. Indoor air BBzP and urinary metabolite concentrations were correlated positively (Spearman's rho 0.40). By contrast, indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations. Vinyl flooring in the home may be an important source of children's exposure to BBzP via indoor air. |
Persistent associations between maternal prenatal exposure to phthalates on child IQ at age 7 years
Factor-Litvak P , Insel B , Calafat AM , Liu X , Perera F , Rauh VA , Whyatt RM . PLoS One 2014 9 (12) e114003 BACKGROUND: Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age. METHODS: In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ). RESULTS: Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = -2.69 (95% confidence interval [CI] = -4.33, -1.05) and b = -2.69 (95% CI = -4.22, -1.16) per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4) and 7.6 (95% CI = 3.2, 12.1) points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning. CONCLUSION: Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children's intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance. |
Asthma in inner-city children at 5-11 years of age and prenatal exposure to phthalates: the Columbia Center for Children's Environmental Health cohort
Whyatt RM , Perzanowski MS , Just AC , Rundle AG , Donohue KM , Calafat AM , Hoepner LA , Perera FP , Miller RL . Environ Health Perspect 2014 122 (10) 1141-6 BACKGROUND: Studies suggest that phthalate exposures may adversely affect child respiratory health. OBJECTIVES: We evaluated associations between asthma diagnosed in children between 5 and 11 years of age and prenatal exposures to butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), and diethyl phthalate (DEP). METHODS: Phthalate metabolites were measured in spot urine collected from 300 pregnant inner-city women. Children were examined by an allergist or pulmonologist based on the first parental report of wheeze, other respiratory symptoms, and/or use of asthma rescue/controller medication in the preceding 12 months on repeat follow-up questionnaires. Standardized diagnostic criteria were used to classify these children as either having or not having current asthma at the time of the physician examination. Children without any report of wheeze or the other asthma-like symptoms were classified as nonasthmatics at the time of the last negative questionnaire. Modified Poisson regression analyses were used to estimate relative risks (RR) controlling for specific gravity and potential confounders. RESULTS: Of 300 children, 154 (51%) were examined by a physician because of reports of wheeze, other asthma-like symptoms, and/or medication use; 94 were diagnosed with current asthma and 60 without current asthma. The remaining 146 children were classified as nonasthmatic. Compared with levels in nonasthmatics, prenatal metabolites of BBzP and DnBP were associated with a history of asthma-like symptoms (p < 0.05) and with the diagnosis of current asthma: RR = 1.17 (95% CI: 1.01, 1.35) and RR = 1.25 (95% CI: 1.04, 1.51) per natural log-unit increase, respectively. Risk of current asthma was > 70% higher among children with maternal prenatal BBzP and DnBP metabolite concentrations in the third versus the first tertile. CONCLUSION: Prenatal exposure to BBzP and DnBP may increase the risk of asthma among inner-city children. However, because this is the first such finding, results require replication. |
Prenatal phthalate and early childhood bisphenol A exposures increase asthma risk in inner-city children
Whyatt RM , Rundle AG , Perzanowski MS , Just AC , Donohue KM , Calafat AM , Hoepner L , Perera FP , Miller RL . J Allergy Clin Immunol 2014 We previously reported that inner-city childhood asthma was associated independently with measures of early childhood exposure to bisphenol A (BPA)1and prenatal, but not childhood, exposures to di-n-butyl phthalate (DnBP) and butylbenzyl phthalate (BBzP).2 Here we evaluate whether these two classes of endocrine disrupting chemicals (EDCs) interact to increase risk of asthma. |
Misuse of blood serum to assess exposure to bisphenol A and phthalates
Calafat AM , Koch HM , Swan SH , Hauser R , Goldman LR , Lanphear BP , Longnecker MP , Rudel RA , Teitelbaum SL , Whyatt RM , Wolff MS . Breast Cancer Res 2013 15 (5) 403 We noted serious methodologic issues in the measurement of bisphenol A (BPA), phthalate diesters, and their metabolites in blood serum and other tissues, as reported in the recent Breast Cancer Research article by Sprague and colleagues [1]. Such measurements are analytically possible. However, for the reasons that follow, it is seldom possible to verify that serum concentrations of these compounds are valid measures of exposure. | | BPA and phthalate diesters are non-persistent in the body; they metabolize quickly and, as a result, the levels of their polar, hydrophilic metabolites in blood can be several orders of magnitude lower than in urine (controlled human studies suggest 30- to 100-fold higher levels in urine than serum) [2-4]. Such low levels increase the possibility that contamination can obscure true exposures. | | Extraneous sources of phthalate diesters include plastics, personal care and consumer products, and building furnishings [2,5]. Phthalate diesters derived externally can easily contaminate blood serum and other human matrices and overwhelm the very low levels in blood from daily exposures [2,4]. Hydrolytic enzymes are ubiquitous in blood and most other matrices (but not urine). These enzymes rapidly hydrolyze extraneous phthalate diesters to their corresponding monoesters, beginning immediately after sample collection, and this can artificially elevate the concentrations of these hydrolytic monoesters, including monoethyl phthalate and mono-(2-ethylhexyl) phthalate. To the best of our knowledge, phthalate oxidative metabolites (such as mono-(2-ethyl-5-oxohexyl) phthalate) do not form as a result of recent external contamination. The oxidative metabolites were not measured in the study by Sprague and colleagues [1]. Therefore, in blood, saliva, or tissues other than urine, only the phthalate oxidative metabolites (not the phthalate diesters or the hydrolytic monoesters) are valid exposure biomarkers. |
Predictors of serum concentrations of polybrominated flame retardants among healthy pregnant women in an urban environment: a cross-sectional study
Horton MK , Bousleiman S , Jones R , Sjodin A , Liu X , Whyatt R , Wapner R , Factor-Litvak P . Environ Health 2013 12 (1) 23 BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants commonly used in a wide range of products. Prenatal exposure to PBDEs has been associated with adverse neurodevelopment. Our objective was to characterize predictors of exposure to PBDEs among a multi-ethnic, low-income cohort of pregnant women enrolled from highly urban communities in New York City between years 2009-2010. METHODS: During the first half of pregnancy we collected 316 maternal serum samples and administered an extensive questionnaire including items on demographics, diet and lifestyle. We measured 12 PBDE congeners in blood samples. Using bivariate and multivariate approaches, we regressed the most commonly detected PBDE congeners (PBDE-47, -99, -100 and -153) against potential demographic, dietary and lifestyle predictor variables. RESULTS: At least one PBDE congener was detected in each serum sample. Our analyses demonstrate unique predictor patterns for PBDE-47, -99, -100 and -153 based on demographic, lifestyle and dietary characteristics of women. Higher education and increased use of household electronics were associated with higher levels of all 4 congeners. Six characteristics were associated with PBDE-153 serum concentrations, more than for any other congener. These include maternal education, household income, body mass index, solid dairy consumption, processed meat consumption and frequent use of household electronics. CONCLUSIONS: PBDE exposure in this widespread in this cohort, though levels are lower than previous assessments of US pregnant women. Lower levels may be in response to legislation restricting the production, sale and use of these compounds. In our cohort, we did not observe any individual predictor or a consistent pattern of several predictors representing a significant source of PBDE exposure. These data suggest that legislation and policy may be more effective at reducing exposure than personal lifestyle modifications. |
Urinary concentrations of bisphenol A in an urban minority birth cohort in New York City, prenatal through age 7 years
Hoepner LA , Whyatt RM , Just AC , Calafat AM , Perera FP , Rundle AG . Environ Res 2013 122 38-44 BACKGROUND: Despite growing concern over potential health effects associated with exposures to the endocrine disruptor, bisphenol A (BPA), insufficient information is available on determinants of BPA concentrations among minority populations in the US. OBJECTIVES: To describe concentrations and predictors of BPA in an inner-city longitudinal birth cohort. METHODS: We analyzed spot urines for total BPA collected during pregnancy and child ages 3, 5, and 7 years from African Americans and Dominicans (n=568) enrolled in the Columbia Center for Children's Environmental Health birth cohort and residing in Northern Manhattan and the South Bronx. Adjusting for specific gravity, generalized estimating equations were used to compare BPA concentrations across paired samples and linear regression analyses were used to determine relationships between BPA, season of sample collection, socio-demographic variables and urinary concentrations of phthalate metabolites. RESULTS: BPA was detected in ≥94% of samples. Prenatal concentrations were significantly lower than postnatal concentrations. Geometric means were higher among African Americans compared to Dominicans in prenatal (p=0.008), 5 year (p<0.001) and 7 year (p=0.017) samples. Geometric means at 5 and 7 years were higher (p=0.021, p=0.041 respectively) for children of mothers never married compared to mothers ever married at enrollment. BPA concentrations were correlated with phthalate metabolite concentrations at prenatal, 3, 5 and 7 years (p-values <0.05). Postnatal BPA concentrations were higher in samples collected during the summer. CONCLUSIONS: This study shows widespread BPA exposure in an inner-city minority population. BPA concentration variations were associated with socio-demographic characteristics and other xenobiotics. |
Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children
Donohue KM , Miller RL , Perzanowski MS , Just AC , Hoepner LA , Arunajadai S , Canfield S , Resnick D , Calafat AM , Perera FP , Whyatt RM . J Allergy Clin Immunol 2013 131 (3) 736-742 e6 BACKGROUND: Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation. OBJECTIVES: We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (Feno) values in children. METHODS: The Columbia Center for Children's Environmental Health recruited pregnant women for a prospective birth cohort study (n = 568). Mothers during the third trimester and children at ages 3, 5, and 7 years provided spot urine samples. Total urinary BPA concentrations were measured by using online solid-phase extraction, high-performance liquid chromatography, isotope-dilution tandem mass spectrometry. Wheeze in the last 12 months was measured by using questionnaires at ages 5, 6, and 7 years. Asthma was determined by a physician once between ages 5 and 12 years. Feno values were measured at ages 7 to 11 years. RESULTS: Prenatal urinary BPA concentrations were associated inversely with wheeze at age 5 years (odds ratio [OR], 0.7; 95% CI, 0.5-0.9; P = .02). Urinary BPA concentrations at age 3 years were associated positively with wheeze at ages 5 years (OR, 1.4; 95% CI, 1.1-1.8; P = .02) and 6 years (OR, 1.4; 95% CI, 1.0-1.9; P = .03). BPA concentrations at age 7 years were associated with wheeze at age 7 years (OR, 1.4; 95% CI, 1.0-1.9; P = .04) and Feno values (beta = 0.1; 95% CI, 0.02-0.2; P = .02). BPA concentrations at ages 3, 5, and 7 years were associated with asthma (OR, 1.5 [95% CI, 1.1-2.0], P = .005; OR, 1.4 [95% CI, 1.0-1.9], P = .03; and OR, 1.5 [95% CI, 1.0-2.1], P = .04, respectively). CONCLUSIONS: This is the first report of an association between postnatal urinary BPA concentrations and asthma in children. |
Prenatal exposure to butylbenzyl phthalate and early eczema in an urban cohort
Just AC , Whyatt RM , Perzanowski MS , Calafat AM , Perera FP , Goldstein IF , Chen Q , Rundle AG , Miller RL . Environ Health Perspect 2012 120 (10) 1475-80 BACKGROUND: Recent cross-sectional studies suggest a link between butylbenzyl phthalate (BBzP) in house dust and childhood eczema. OBJECTIVES: We aimed to evaluate whether concentrations of monobenzyl phthalate (MBzP), the main BBzP metabolite in urine, during pregnancy are associated prospectively with eczema in young children, and whether this association varies by the child's sensitization to indoor allergens or serological evidence of any allergies. METHODS: MBzP was measured in spot urine samples during the third trimester of pregnancy from 407 African-American and Dominican women residing in New York City in 1999-2006. Repeated questionnaires asked mothers whether their doctor ever said their child had eczema. Child blood samples at 24, 36, and 60 months of age were analyzed for total, anti-cockroach, dust mite, and mouse IgE. Relative risks (RR) were estimated with multivariable modified Poisson regression. Analyses included a multinomial logistic regression model for early- and late-onset eczema versus no eczema through 60 months of age. RESULTS: MBzP was detected in > 99% of samples (geometric mean = 13.6; interquartile range: 5.7-31.1 ng/mL). By 24 months, 30% of children developed eczema, with the proportion higher among African Americans (48%) than among Dominicans (21%) (p < 0.001). An interquartile range increase in log MBzP concentration was associated positively with early-onset eczema (RR = 1.52 for eczema by 24 months; 95% confidence interval: 1.21, 1.91, p = 0.0003, n = 113 reporting eczema/376 total sample), adjusting for urine specific gravity, sex, and race/ethnicity. MBzP was not associated with allergic sensitization, nor did seroatopy modify consistently the MBzP and eczema association. CONCLUSIONS: Prenatal exposure to BBzP may influence the risk of developing eczema in early childhood. |
Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor, and behavioral development at 3 years of age
Whyatt RM , Liu X , Rauh VA , Calafat AM , Just AC , Hoepner L , Diaz D , Quinn J , Adibi J , Perera FP , Factor-Litvak P . Environ Health Perspect 2012 120 (2) 290-5 BACKGROUND: Research suggests that prenatal phthalate exposures affect child executive function and behavior. OBJECTIVE: We evaluated associations between phthalate metabolite concentrations in maternal prenatal urine and mental, motor, and behavioral development in children at 3 years of age. METHODS: Mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), and four di-2-ethylhexyl phthalate metabolites were measured in a spot urine sample collected from 319 women during the third trimester. When children were 3 years of age, the Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using the Bayley Scales of Infant Development II, and behavior problems were assessed by maternal report on the Child Behavior Checklist. RESULTS: Child PDI scores decreased with increasing loge MnBP [estimated adjusted beta-coefficient = -2.81; 95% confidence interval (CI): -4.63, -1.0] and loge MiBP (beta = -2.28; 95% CI: -3.90, -0.67); odds of motor delay increased significantly [per loge MnBP: estimated adjusted odds ratio (OR) = 1.64; 95% CI: 1.10, 2.44; per loge MiBP: adjusted OR =1.82; 95% CI: 1.24, 2.66]. In girls, MDI scores decreased with increasing loge MnBP (beta = -2.67; 95% CI: -4.70, -0.65); the child sex difference in odds of mental delay was significant (p = 0.037). The ORs for clinically withdrawn behavior were 2.23 (95% CI: 1.27, 3.92) and 1.57 (95% CI: 1.07, 2.31) per loge unit increase in MnBP and MBzP, respectively; for clinically internalizing behaviors, the OR was 1.43 (95% CI: 1.01, 1.90) per loge unit increase in MBzP. Significant child sex differences were seen in associations between MnBP and MBzP and behaviors in internalizing domains (p < 0.05). CONCLUSION: Certain prenatal phthalate exposures may decrease child mental and motor development and increase internalizing behaviors. |
Polycyclic aromatic hydrocarbon metabolite levels and pediatric allergy and asthma in an inner-city cohort
Miller RL , Garfinkel R , Lendor C , Hoepner L , Li Z , Romanoff L , Sjodin A , Needham L , Perera FP , Whyatt RM . Pediatr Allergy Immunol 2010 21 260-7 Exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with allergic sensitization and asthma. We hypothesized that increased urinary PAH metabolites are associated with allergy or asthma among children age 5 yrs in an inner-city birth cohort. As part of an ongoing prospective birth cohort under the auspices of the Columbia Center for Children's Environmental Health (CCCEH), urine was collected from 5-yr-old children (n = 222) of Dominican American and African American mothers in Northern Manhattan and South Bronx of New York City. Twenty-four PAH metabolites were measured in these specimens, and their levels (unadjusted and specific gravity corrected) were evaluated with IgE levels and asthma outcomes. Ten metabolites were detected in urine from all children. Concentrations ranged higher than those in representative samples of US children ages 6-11 in the National Health and Nutrition Examination Survey (NHANES). Among CCCEH children, compared with African Americans, the Dominican children had higher 2-hydroxynaphthalene but lower 9-hydroxyfluorene and 4-hydroxyphenanthrene concentrations. Increased 3-hydroxyfluorene and 3-hydroxyphenanthrene levels were associated with higher anti-mouse IgE levels (p < 0.05). These plus 2-hydroxynaphthalene, 2-hydroxyflourene and 1-hydroxyphenanthrene concentrations were associated with higher anti-mouse IgE levels on multivariate analyzes. Increased 2-hydroxyphenanthrene, 3-hydroxyphenanthrene and 4-hydroxyphenanthrene levels were associated with higher anti-cat IgE levels (p < 0.05) in univariate, but not multivariate, analyzes. Levels of PAH metabolites were not associated with respiratory symptoms. Measures of PAH metabolites suggest considerable exposure in an urban pediatric population, and possible associations with allergic sensitization to mouse. |
Measurement of pyrethroid, organophosphorus, and carbamate insecticides in human plasma using isotope dilution gas chromatography-high resolution mass spectrometry
Perez JJ , Williams MK , Weerasekera G , Smith K , Whyatt RM , Needham LL , Barr DB . J Chromatogr B Analyt Technol Biomed Life Sci 2010 878 (27) 2554-62 We have developed a gas chromatography-high resolution mass spectrometry method for measuring pyrethroid, organophosphorus, carbamate and fipronil pesticides and the synergist piperonyl butoxide in human plasma. Plasma samples were extracted using solid phase extraction and were then concentrated for injection and analysis using isotope dilution gas chromatography-high resolution mass spectrometry. The limits of detection ranged from 10 to 158pg/mL with relative recoveries at concentrations near the LODs (e.g., 25 or 250pg/mL) ranging from 87% to 156% (9 of the 16 compounds were within +/-15% of 100%). The extraction recoveries ranged from 20% to 98% and the overall method relative standard deviations were typically less than 20% with some exceptions. Analytical characteristics were determined at 25, 250, and 1000pg/mL. |
Transcriptional biomarkers of steroidogenesis and trophoblast differentiation in the placenta in relation to prenatal phthalate exposure
Adibi JJ , Whyatt RM , Hauser R , Bhat HK , Davis BJ , Calafat AM , Hoepner LA , Perera FP , Tang D , Williams PL . Environ Health Perspect 2010 118 (2) 291-6 Background: Phthalates can alter steroidogenesis and peroxisome proliferatoractivated receptor gamma (PPARgamma)mediated transcription in rodent tissues. The placenta offers a rich source of biomarkers to study these relationships in humans. Objective: We evaluated whether gestational phthalate exposures in humans were associated with altered human placental steroidogenesis and trophoblast differentiation as measured by markers of mRNA transcription. Methods: We measured seven target genes in placentas collected from 54 Dominican and African-American women at delivery in New York City using quantitative real-time polymerase chain reaction (qPCR), normalized to 18S rRNA. qPCR results for the target genes were log-transformed, converted to Z-scores, and grouped into two functional pathways: steroidogenesis (aromatase, cholesterol side chain cleavage enzyme, 17beta-hydroxysteroid dehydrogenase type 1, and cytochrome P450 1B1) and trophoblast differentiation (PPARgamma, aryl hydrocarbon receptor, and human chorionic gonadotropin). Repeated measures models were used to evaluate the association of phthalate metabolites measured in third-trimester urine samples with each group of target genes, accounting for correlation among the genes within a pathway. Results: Higher urinary concentrations of five phthalate metabolites were associated with lower expression of the target genes reflecting trophoblast differentiation. Results were less consistent for genes in the steroidogenesis pathway and suggested a nonlinear doseresponse pattern for some phthalate metabolites. Conclusions: We observed a significant association between prenatal exposure to phthalates and placental gene expression within two pathways. Further studies are warranted to understand the significance of this association with respect to fetal development and placental function. Editor's Summary: In vitro systems to identify and characterize effects of endocrine-active chemicals (EACs) may reduce screening costs, testing time, and animal use while providing an experimental platform to characterize molecular and biochemical effects of exposure. The human adrenocortical carcinoma cell line H295R expresses all key enzymes involved in the synthesis of adrenocorticol steroid hormones from cholesterol and is being evaluated as a potential screening assay for EACs with effects on steroid biosynthesis. Breen et al. (p. 265) developed a mechanistic computational model to estimate the synthesis and secretion of 14 adrenal steroids in H295R cells and biochemical responses to enzyme inhibition by the model EAC metryrapone (MET), and they compared model estimates with time-course measurements in control and MET-exposed H295R cells. The authors report that predictions corresponded well with observed effects overall and conclude that results support the utility of this approach. They suggest that additional model development can facilitate research on unknown mechanisms of action and effects of chemical mixtures, and may improve the accuracy of low-dose extrapolations for risk assessment. |
Regional bumps: case studies from the 1958 bump symposium
Whyatt J , Varley F . Trans Soc Min Metall Explor Inc 2010 326 101-105 A variety of dynamic failure cases with regional impact were described at a bump symposium held in 1958. These types of events, while rare, are of particular interest because their ability to impact a large area has disaster potential. These cases can be grouped into two broad classes of events by mechanism. These are (1) a slip along steeply dipping faults and (2) the fracturing of strong strata above or below the coal seam. Both failure modes produce dynamic or "shock" loads on the perimeter (roof, rib and floor) of mine openings. Special consideration should be given to these failure modes in the planning of deep coal mines, since their occurrence is not within the professional experience of many contemporary workers. In addition, their potential is not evaluated by many of the analysis tools commonly used to evaluate hazards in coal mine plans. |
Prenatal di(2-ethylhexyl)phthalate exposure and length of gestation among an inner-city cohort
Whyatt RM , Adibi JJ , Calafat AM , Camann DE , Rauh V , Bhat HK , Perera FP , Andrews H , Just AC , Hoepner L , Tang D , Hauser R . Pediatrics 2009 124 (6) e1213-20 OBJECTIVE: Our objective was to assess the relationship between di(2-ethylhexyl)phthalate (DEHP) exposure during pregnancy and gestational age at delivery among 311 African American or Dominican women from New York City. METHODS: Forty-eight-hour personal air and/or spot urine samples were collected during the third trimester. DEHP levels were measured in air samples and 4 DEHP metabolite levels were measured in urine. Specific gravity was used to adjust for urinary dilution. Gestational age was abstracted from newborn medical records (n = 289) or calculated from the expected date of delivery (n = 42). Multivariate linear regression models controlled for potential confounders. RESULTS: DEHP was detected in 100% of personal air samples (geometric mean: 0.20 microg/m(3) [95% confidence interval [CI]: 0.18-0.21 microg/m(3)]); natural logarithms of air concentrations were inversely but not significantly associated with gestational age. Two or more of the DEHP metabolites were detected in 100% of urine samples (geometric mean: 4.8-38.9 ng/mL [95% CI: 4.1-44.3 ng/mL]). Controlling for potential confounders, gestational age was shorter by 1.1 days (95% CI: 0.2-1.8 days) for each 1-logarithmic unit increase in specific gravity-adjusted mono(2-ethylhexyl)phthalate concentrations (P = .01) and averaged 5.0 days (95% CI: 2.1-8.0 days) less among subjects with the highest versus lowest quartile concentrations (P = .001). Results were similar and statistically significant for the other DEHP metabolites. CONCLUSIONS: Prenatal DEHP exposure was associated with shorter gestation but, given inconsistencies with previous findings for other study populations, results should be interpreted with caution, and additional research is warranted. |
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