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BACKGROUND: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. OBJECTIVES: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). METHODS: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. RESULTS: We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1[sub 192RR] genotype, ΣDAP and ΣDMP were negatively associated with length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.5 cm; 95% CI:-0.9, -0.1). CONCLUSIONS: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1[sub 192RR] genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001. Objectives: We conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months. METHODS: Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (Σ) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype. RESULTS: There was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics. CONCLUSIONS: Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent organic diet intervention studies suggest that diet is a significant source of pesticide exposure in young children. These studies have focused on children living in suburban communities. OBJECTIVES: We aimed to determine whether consuming an organic diet reduced urinary pesticide metabolite concentrations in 40 Mexican-American children, 3-6 years of age, living in California urban and agricultural communities. METHODS: In 2006, we collected urine samples over 16 consecutive days from children who consumed conventionally grown food for 4 days, organic food for 7 days, and then conventionally grown food for 5 days. We measured 23 metabolites, reflecting potential exposure to organophos-phorous (OP), pyrethroid, and other pesticides used in homes and agriculture. We used linear mixed-effects models to evaluate the effects of diet on urinary metabolite concentrations. RESULTS: For six metabolites with detection frequencies > 50%, adjusted geometric mean concentrations during the organic phase were generally lower for all children, and were significant for total dialkylphosphates (DAPs) and dimethyl DAPs (DMs; metabolites of OP insecticides) and 2,4-D (2,4-dichlorophenoxyacetic acid, a herbicide), with reductions of 40%, 49%, and 25%, respectively (p < 0.01). Chemical-specific metabolite concentrations for several OP pesticides, pyrethroids, and herbicides were either infrequently detected and/or not significantly affected by diet. Concentrations for most of the frequently detected metabolites were generally higher in Salinas compared with Oakland children, with DMs and metolachlor at or near significance (p = 0.06 and 0.03, respectively). CONCLUSION: An organic diet was significantly associated with reduced urinary concentrations of nonspecific dimethyl OP insecticide metabolites and the herbicide 2,4-D in children. Additional research is needed to clarify the relative importance of dietary and non-dietary sources of pesticide exposures to young children. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA), a widely used endocrine-disrupting chemical, has been associated with increased body weight and fat deposition in rodents. Objectives: We examined whether prenatal and postnatal urinary BPA concentrations were associated with body mass index (BMI), waist circumference, percent body fat, and obesity in 9-year-old children (n = 311) in the CHAMACOS longitudinal cohort study. Methods: BPA was measured in spot urine samples collected from mothers twice during pregnancy and from children at 5 and 9 years of age. Results: Prenatal urinary BPA concentrations were associated with decreased BMI at 9 years of age in girls but not boys. Among girls, being in the highest tertile of prenatal BPA concentrations was associated with decreased BMI z-score (β = -0.47, 95% CI: -0.87, -0.07) and percent body fat (β = -4.36, 95% CI: -8.37, -0.34) and decreased odds of overweight/obesity [odds ratio (OR) = 0.37, 95% CI: 0.16, 0.91] compared with girls in the lowest tertile. These findings were strongest in prepubertal girls. Urinary BPA concentrations at 5 years of age were not associated with any anthropometric parameters at 5 or 9 years, but BPA concentrations at 9 years were positively associated with BMI, waist circumference, fat mass, and overweight/obesity at 9 years in boys and girls. Conclusions: Consistent with other cross-sectional studies, higher urinary BPA concentrations at 9 years of age were associated with increased adiposity at 9 years. However, increasing BPA concentrations in mothers during pregnancy were associated with decreased BMI, body fat, and overweight/obesity among their daughters at 9 years of age. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the utility of urinary Clara cell protein (CC16) as a biomarker of increased lung epithelial permeability in non-smokers exposed to outdoor secondhand smoke. Twenty-eight healthy non-smoking adults visited outdoor patios of a restaurant and a bar where non-participants smoked and an open-air control with no smokers on three weekend days in a crossover study; subjects visited each site once for 3 h. Urine samples were collected at baseline, immediately post exposure and next morning, and analyzed for CC16. Changes in CC16 across location types or with cigarette count were analyzed using mixed-effect models, which included all subjects and stratified by gender. Urinary CC16 was higher in males (n=9) compared with females (n=18) at all measurement occasions (P<0.002), possibly reflecting prostatic contamination. Urinary CC16 from pre-exposure to post-exposure was higher following visits to restaurant and bar sites compared with the control among females but this increase did not reach statistical significance. Post-exposure to pre-exposure urinary CC16 ratios among females increased with cigarette count (P=0.048). Exposure-related increases in urinary CC16 were not seen among males. In conclusion, urinary CC16 may be a useful biomarker of increased lung epithelial permeability among female non-smokers; further work will be required to evaluate its applicability to males. [ABSTRACT FROM AUTHOR]

Background: Bisphenol 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. Objective: Our goal was to evaluate whether exposure to BPA during pregnancy is related to thyroid hormone levels in pregnant women and neonates. Methods: We 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. Results: Associations 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. Conclusion: Results 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. [ABSTRACT FROM AUTHOR]

Background: Dialkyl phosphate (DAP) metabolites in spot urine samples are frequently used to characterize children's exposures to organophosphorous (OP) pesticides. However, variable exposure and short biological half-lives of OP pesticides could result in highly variable measurements, leading to exposure misclassification. Objective: We examined within- and between-child variability in DAP metabolites in urine samples collected during 1 week. Methods: We collected spot urine samples over 7 consecutive days from 25 children (3-6 years of age). On two of the days, we collected 24-hr voids. We assessed the reproducibility of urinary DAP metabolite concentrations and evaluated the sensitivity and specificity of spot urine samples as predictors of high (top 20%) or elevated (top 40%) weekly average DAP metabolite concentrations. Results: Within-child variance exceeded between-child variance by a factor of two to eight, depending on metabolite grouping. Although total DAP concentrations in single spot urine samples were moderately to strongly associated with concentrations in same-day 24-hr samples (r ≈ 0.6.0.8, p < 0.01), concentrations in spot samples collected > 1 day apart and in 24-hr samples collected 3 days apart were weakly correlated (r ≈ .0.21 to 0.38). Single spot samples predicted high (top 20%) and elevated (top 40%) full-week average total DAP excretion with only moderate sensitivity (≈ 0.52 and ≈ 0.67, respectively) but relatively high specificity (≈ 0.88 and ≈ 0.78, respectively). Conclusions: The high variability we observed in children's DAP metabolite concentrations suggests that single-day urine samples provide only a brief snapshot of exposure. Sensitivity analyses suggest that classification of cumulative OP exposure based on spot samples is prone to type 2 classification errors. [ABSTRACT FROM AUTHOR]

Exposure to organophosphate and carbamate pesticides can lead to neurotoxic effects through inhibition of Cholinesterase enzymes. The paraoxonase {PON 1) enzyme can detoxify oxon derivatives of some organophosphates. Lower POA/1, acetylcholinesterase, and butyrylcholinesterase activities have been reported In newborns relative to adults, suggesting increased susceptibility to organophosphate exposure in young children. We determined PON 1, acetylcholinesterase, and butyrylcholinesterase activities in Mexican-American mothers and their 9-year-old children (n = 202 pairs) living in an agricultural community. We used Wllcoxon signed-rank tests to compare enzymatic activities among mothers and their children, and analysis of variance to identify factors associated with enzyme activities. Substrate-specific PONI activities were slightly lower In children than their mothers; however, these differences were only statistically significant for the paraoxon substrate. We observed significantly lower acetylcholinesterase but higher butyrylcholinesterase levels in children compared with their mothers. Mean butyrylcholinesterase levels were strongly associated with child obesity status (body mass index Z scores >95%). We observed highly significant correlations among mother-child pairs for each of the enzymatic activities analyzed; however, PON1 activities did not correlate with acetylcholinesterase or butyrylcholinesterase activities. Our findings suggest that by age 9 years, PON1 activities approach adult levels, and host factors including sex and obesity may affect key enzymes involved in pesticide metabolism. [ABSTRACT FROM AUTHOR]

Background: With an increase in indoor smoking bans, many smokers smoke outside establishments and near their entrances, which has become a public health concern. Objectives: We characterized the exposure of nonsmokers to secondhand smoke (SHS) outside a restaurant and bar in Athens, Georgia, where indoor smoking is banned, using salivary cotinine and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Methods: In a crossover study, we assigned 28 participants to outdoor patios of a restaurant and a bar and an open-air site with no smokers on three weekend days; participants visited each site once and stayed for 3 hr. We collected saliva and urine samples immediately before and after the visits (postexposure) and on the following morning and analyzed samples for cotinine and total NNAL, respectively. Regression models were fitted and changes in biomarkers were contrasted between locations. Results: Postexposure and preexposure geometric mean salivary cotinine concentrations differed by 0.115 ng/mL [95% confidence interval (CI): 0.105, 0.126)] and by 0.030 ng/mL (95% CI: 0.028, 0.031) for bar and restaurant visits, respectively. There were no significant post- and preexposure differences in cotinine levels after control site visits, and changes after bar and restaurant site visits were significantly different from changes after control site visits (p < 0.001). Results comparing next-day and preexposure salivary cotinine levels were similar. Next-day creatinine-corrected urinary NNAL concentrations also were higher than preexposure levels following bar and restaurant visits [1.858 pg/mg creatinine higher (95% CI: 0.897, 3.758) and 0.615 pg/mg creatinine higher (95% CI: 0.210, 1.761), respectively], and were significantly different from changes after the control visits (p = 0.005). Conclusion: Salivary cotinine and urinary NNAL increased significantly in nonsmokers after outdoor SHS exposure. Our findings indicate that such exposures may increase risks of health effects associated with tobacco carcinogens. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association. Methods: The study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1192 and PON12108) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records. Results: Infants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON12108TT genotype had shorter gestational age (b =20.5 weeks, 95% Confidence Interval (CI): 20.9, 0.0) and smaller head circumference (b =20.4 cm, 95% CI: 20.7, 0.0) than those with the PON12108CC genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON12108TT genotype (p-valueinteraction = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-valueinteraction = 0.06) and head circumference (p-valueinteraction,0.01) in infants with non-susceptible genotypes. Conclusions: Infants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth. [ABSTRACT FROM AUTHOR]

Organochlorine (OC) pesticide use was restricted starting in the 1970s in developed countries and the 1980s and 1990s in developing countries. Current exposure to OC pesticides — dichlorodiphenyltrichloroethane (DDT), lindane (99% pure gamma-hexachlorocyclohexane (γ-HCH)), hexachlorobenzene (HCB) — occurs on a limited basis. We measured para, para' (p,p′)-DDE, p,p′-DDT, ortho, para′ (o,p′)-DDT, HCB, beta (β)-HCH (the most persistent isomer of technical-grade HCH) and γ-HCH in serum from 426 low-income pregnant Latina women living in an agricultural community in California. Detection frequencies were 94% to 100%. Median levels (ng/g lipid) of p,p′-DDE (1,052), p,p′-DDT (13), β-HCH (37) and HCB (65) were significantly higher than United States population levels. Multivariate analyses of p,p′-DDE, p,p′-DDT, o,p′-DDT, β-HCH and HCB indicate that time spent living outside the United States and birthplace in an area of Mexico with recent use of OC pesticides were significant predictors of exposure. Time spent living in the United States was associated with increased serum levels of p,p′-DDE and β-HCH, but the increase for each year lived in the United States was lower than for each year lived outside the United States. There was no difference between the increase of HCB levels over time spent in or outside the United States, suggesting current and thus preventable exposure routes. However, we observed no associations between serum levels of any OC compound and current intake of saturated fat or agricultural take-home exposure risk factors. Lactation history and recent weight gain were negatively associated with serum levels of some, but not all OC compounds studied. Smoking history was borderline associated with elevated HCB levels. We observed no significant associations with body mass index. Although the weight of evidence from this study indicates that most exposure occurred before moving to the United States, the results for HCB indicate the possibility of ongoing exposure in this country.Journal of Exposure Science and Environmental Epidemiology (2007) 17, 388–399; doi:10.1038/sj.jes.7500525; published online 11 October 2006 [ABSTRACT FROM AUTHOR]

BACKGROUND: Children who reside in agricultural settings are potentially exposed to higher levels of organophosphate (OP) pesticides, endotoxin, and allergens than their urban counterparts. Endotoxin and allergens stimulate maturation of the immune response in early childhood, but little is known about the effect of exposures to OPs or to the three combined. OBJECTIVES: In this study, we investigated the relationships between these exposures and T-helper 1 (Th1) and T-helper 2 (Th2) cytokines, biomarkers of allergic asthma, in the subjects of CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort in Salinas Valley, California. Exposures were ascertained by interviewer-administered questionnaires and by home visits, and clinical diagnoses were abstracted from medical records. Blood samples were collected at 12 and 24 months of age and analyzed for Th1/Th2 status by flow cytometric detection of intracellular interferon-γ/interleukin-4 cytokine expression. FINDINGS: Mean Th2 levels were significantly higher in children with doctor-diagnosed asthma and children with wheezing at 2 years of age. In a multiple linear regression model, exclusive breast-feeding at 1 month and pet ownership were associated with 35.3% (p < 0.01) and 34.5% (p = 0.01) increases in Th1, respectively. Maternal agricultural work and presence of gas stove in the home were associated with a 25.9% increase (p = 0.04) and 46.5% increase (p < 0.01) in Th2, respectively. CONCLUSIONS: Asthma and wheeze outcomes in children at 24 months of age are associated with elevated Th2 status in children at an early age. Our data further suggest that early exposures to an agricultural environment, breast-feeding, pets, and gas stoves affect the development of children's Th1/Th2 immune response. [ABSTRACT FROM AUTHOR]

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In anticipation of the National Children's Study, lessons can be learned from the smaller birth cohort studies conducted by five Centers for Children's Environmental Health and Disease Prevention Research funded by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. The populations studied are diverse in ethnicity and social class and reside in urban and rural environments. Although almost all of the centers chose to enroll participants through medical care facilities, they had to develop independent staffs and structures because of the overburdened medical care system. Some of the lessons learned by the centers include the importance of continuous funding, building community partnerships to conduct culturally appropriate research, hiring bilingual and bicultural staff from the community, prioritizing research goals, developing biorepositories to ensure future utility of samples, instituting quality control procedures for all aspects of specimen and data collection, maintaining frequent contact with study participants, ensuring ethical conduct of the research in a changing medical-legal climate, and communicating results in a timely and appropriate manner to participants and the wider community. All centers underestimated the necessary start-up time, staff, and costs in conducting these birth cohort studies. Despite the logistical complexity and added expenses, all centers emphasize the importance of studying the impact of environmental exposures on those children most at risk, those living in minority and low-income communities. These centers present barriers encountered, solutions found, and considerations for future research, with the hope that the lessons learned can help inform the planning and conduct of the National Children's Study. [ABSTRACT FROM AUTHOR]

Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O, O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures. However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [βadjusted = -0.41 weeks per log10 unit increase; 95% confidence interval (CI), -0.75--0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (βadjusted = 0.34 weeks per unit increase; 95% CI, 0.13-0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population. [ABSTRACT FROM AUTHOR]

Benzene is an established human carcinogen, producing leukemia, hematotoxicity and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its conversion to phenol and hydroquinone, the latter being oxidized to the highly toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell lines to hydroquinone has previously been shown to cause various forms of genetic damage, including aneusomy and the loss and gain of chromosomes. However, the target cells for leukemogenesis are the pluripotent stem cells or early progenitor cells which carry the CD34 antigen (CD34+ cells). In this study, human cord blood, which is particularly rich in CD34+ cells, was exposed to hydroquinone for 72 h in a medium that favored CD34+ cell survival and growth. CD34+ and CD34– cells were then isolated. Fluorescence in situ hybridization was employed to determine the level of aneusomy of chromosomes 7 and 8 in both cell types. CD34+ cells were generally more susceptible to aneusomy induction by hydroquinone than CD34– cells. Increased trisomy and monosomy of chromosomes 7 and 8 were observed in CD34+ cells (Ptrend < 0.001), whereas in CD34– cells only an increased level of monosomy 7 was detected (Ptrend = 0.002). Particularly striking effects of hydroquinone were observed in CD34+ cells on monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid leukemias, suggesting that these aneusomies produced by hydroquinone in CD34+ cells play a role in benzene-induced leukemogenesis. [ABSTRACT FROM PUBLISHER]

A table is presented that contains data collected during a research work titled "Maternal Urinary Bisphenol A during Pregnancy and Material and Neonatal Thyroid Function in the CHAMACOS Study," which also serves as a supplemental study material for students studying about environmental health.