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Lam T.,Harvard University | Williams P.L.,Harvard University | Lee M.M.,University of Massachusetts Medical School | Korrick S.A.,Harvard University | And 9 more authors.
Environmental Health Perspectives | Year: 2015

Background: Few human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development. Objective: We evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)] with age at attainment of sexual maturity among boys. Methods: From 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ≥ 20 mL in either testis. Results: In adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ≥ 20 mL a mean of 3.1 months (95% CI: –1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: –3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: –1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of βHCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6–9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), βHCH (trend p = 0.01), and p,p´-DDE (p trend = 0.04). No associations were observed between p,p´-DDE and Tanner stage 5 for genitalia growth or TV ≥ 20 mL. Conclusions and relevance: Higher prepubertal serum HCB and βHCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p,p´-DDE was associated with later pubic hair maturation. © 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved. Source


Burns J.S.,Harvard University | Williams P.L.,Samara State Medical University | Sergeyev O.S.,Harvard University | Korrick S.A.,Harvard University | And 13 more authors.
Environmental Health Perspectives | Year: 2012

Background: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. Objective: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. Methods: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders. Results: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, βHCH, and p,p'-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p'-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile. Conclusions: Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height. Source


Lam T.,Harvard University | Lam T.,Quintiles | Williams P.L.,Harvard University | Lee M.M.,University of Massachusetts Medical School | And 11 more authors.
Environment International | Year: 2014

Background: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. Objective: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,. p'-dichlorodiphenyldichloroethylene (p,. p'-DDE)] with male pubertal onset. Methods: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9. year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3. mL in either testis, or stage 2 or greater for genitalia (G2. +), or pubic hair (P2. +). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset. Results: In adjusted models, boys with higher HCB concentrations had later mean ages of TV > 3. mL and P2+ (but not G2+). Mean age at attaining TV > 3. mL was delayed 3.6 (95% CI: - 2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7. months (95% CI: - 1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1. months earlier (95% CI: - 5.8, 5.6) for Q2, 4.7. months later (95% CI: - 1.0, 10.3) for Q3 and 4.6. months later (95% CI: - 1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum β-HCH and p,. p'-DDE concentrations with age of pubertal onset. Conclusion: Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche. © 2014 Elsevier Ltd. Source


Korrick S.A.,Harvard University | Lee M.M.,University of Massachusetts Medical School | Williams P.L.,Harvard University | Sergeyev O.,Samara State Medical University | And 10 more authors.
Environmental Health Perspectives | Year: 2011

Background: Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. bjectives: We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. ethods: Between 2003 and 2005, 499 boys 8-9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment. esults: The median (range) total serum TEQ concentration was 21 (4-175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49-0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses. onclusions: Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation. Source


Lam T.,Harvard University | Williams P.L.,Harvard University | Burns J.S.,Harvard University | Sergeyev O.,Samara State Medical University | And 10 more authors.
Environmental Health Perspectives | Year: 2013

Background: Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals. Objectives: Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p'-DDE)-among boys in Chapaevsk, Russia. Methods: Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and β-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, β-HCH, and p,p'-DDE concentrations. Results: Among 355 boys with OCP measurements, median serum HCB, β-HCH, and p,p'-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and β-HCH concentrations, respectively, than boys who lived ≥ 5 km away. Living > 3 years in Chapaevsk predicted higher β-HCH concentrations, and having parents who lacked a high school education predicted higher p,p'-DDE concentrations. Conclusions: Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex. Source

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