The association of peripubertal serum concentrations of organochlorine chemicals and blood lead with growth and pubertal development in a longitudinal cohort of boys: a review of published results from the Russian Children's Study.
Organochlorine chemicals and lead are environmental exposures that have endocrine disrupting properties (EDCs) which interfere with many aspects of hormone action. Childhood and adolescence are windows of susceptibility for adverse health effects of EDCs. Our ongoing study, the Russian Children's Study (RCS), is one of the few longitudinal studies investigating the impact of EDCs on growth and puberty in boys. It is conducted in the historically contaminated city of Chapaevsk, in the Samara region. The study focuses on evaluating the associations of persistent organochlorine chemicals and lead with growth and pubertal timing. At enrollment in 2003-2005, we collected blood from 516 boys at ages 8-9 years to measure dioxins, furans, polychlorinated biphenyls (PCBs), chlorinated pesticides and lead. At enrollment and at annual visits through the ages of 18-19 years, a physician performed physical examinations that included pubertal staging and testicular volume measurements. We review the history of Chapaevsk as a research site and summarize published RCS data on the association of peripubertal serum concentrations of organochlorines and blood lead levels with growth, pubertal onset and sexual maturity. Overall, we found that persistent organochlorines and lead negatively affected growth during puberty. Our results also suggest that total toxic equivalents (TEQs), dioxin-like compounds, organochlorine pesticides and lead may delay, while nondioxin-like-PCBs may advance, the timing of male puberty. These findings promoted remediation programs in Chapaevsk, with improvement in health indicators, resulting in Chapaevsk being designated a member of the World Health Organization (WHO) network "Healthy Cities" in 2015.
Dioxins, furans, and polychlorinated biphenyls (PCBs), dioxin-like and non-dioxin-like, have been linked to alterations in puberty.
We examined the association of peripubertal serum levels of these compounds [and their toxic equivalents (TEQs)] with pubertal onset and maturity among Russian boys enrolled at ages 8-9 years and followed prospectively through ages 17-18 years.
At enrollment, 473 boys had serum dioxin-like compounds and PCBs measured. At the baseline visit and annually until age 17-18 years, a physician performed pubertal staging [genitalia (G), pubarche (P), and testicular volume (TV)]. Three hundred fifteen subjects completed the follow-up visit at 17-18 years of age. Pubertal onset was defined as TV > 3 mL, G2, or P2. Sexual maturity was defined as TV = 20 mL, G5, or P5. Multivariable interval-censored models were used to evaluate associations of lipid-standardized concentrations with pubertal timing.
Medians (interquartile ranges) of the sum of dioxin-like compounds, TEQs, and non-dioxin-like PCBs were 362 pg/g lipid (279-495), 21.1 pg TEQ/g lipid (14.4-33.2), and 250 ng/g lipid (164-395), respectively. In adjusted models, the highest compared to lowest TEQ quartile was associated with later pubertal onset [TV = 11.6 months (95% CI: 3.8, 19.4); G2 = 10.1 months (95% CI: 1.4, 18.8)] and sexual maturity [TV = 11.6 months (95% CI: 5.7, 17.6); G5 = 9.7 months (95% CI: 3.1, 16.2)]. However, the highest compared to the lowest quartile of non-dioxin-like PCBs, when co-adjusted by TEQs, was associated with earlier pubertal onset [TV = -8.3 months (95% CI:-16.2, -0.3)] and sexual maturity [TV = -6.3 months (95% CI:-12.2, -0.3); G5 = -7.2 months (95% CI:-13.8, -0.6)]; the non-dioxin-like PCB associations were only significant when adjusted for TEQs. TEQs and PCBs were not significantly associated with pubic hair development.
Our results suggest that TEQs may delay, while non-dioxin-like PCBs advance, the timing of male puberty. Citation: Burns JS, Lee MM, Williams PL, Korrick SA, Sergeyev O, Lam T, Revich B, Hauser R. 2016. Associations of peripubertal serum dioxin and polychlorinated biphenyl concentrations with pubertal timing among Russian boys. Environ Health Perspect 124:1801-1807; http://dx.doi.org/10.1289/EHP154.
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We evaluated the association of blood lead levels (BLLs) with pubertal onset in a longitudinal cohort of Russian boys.
A total of 489 Russian boys were enrolled in 2003-2005, at 8 to 9 years of age, and were monitored annually through May 2008. Cox proportional-hazards models were used to evaluate the association of BLLs at enrollment with time to pubertal onset during follow-up monitoring.
A total of 481 boys had BLLs, with a median of 3 microg/dL and 28% with values of > or =5 microg/dL. The proportion of pubertal boys increased with age, from 12% at age 8 to 83% at age 12 for testicular volume of >3 mL, from 22% to 90% for genitalia stage 2 or higher, and from 4% to 40% for pubic hair stage 2 or higher. After adjustment for potential confounders including BMI and height, boys with high BLLs (> or =5 microg/dL) had 24% to 31% reduced risk of pubertal onset, on the basis of testicular volume of >3 mL (hazard ratio [HR]: 0.73 [95% confidence interval [CI]: 0.55-0.97]; P = .03), genitalia staging (HR: 0.76 [95% CI: 0.59-0.98]; P = .04), and pubic hair staging (HR: 0.69 [95% CI: 0.44-1.07]; P = .10), compared with those with lower BLLs. Pubertal onset occurred 6 to 8 months later, on average, for boys with high BLLs, compared with those with BLLs of
Childhood lead exposure has been associated with growth delay. However, the association between blood lead levels (BLLs) and insulin-like growth factor 1 (IGF-1) has not been characterized in a large cohort with low-level lead exposure.
We recruited 394 boys 8-9 years of age from an industrial Russian town in 2003-2005 and followed them annually thereafter. We used linear regression models to estimate the association of baseline BLLs with serum IGF-1 concentration at two follow-up visits (ages 10-11 and 12-13 years), adjusting for demographic and socioeconomic covariates.
At study entry, median BLL was 3 µg/dL (range,
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Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Qu?bec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies.
Animal studies have demonstrated that timing of pubertal onset can be altered by prenatal exposure to dioxins or polychlorinated biphenyls (PCBs), but studies of human populations have been quite limited.
We assessed the association between maternal serum concentrations of dioxins and PCBs and the sons' age of pubertal onset in a prospective cohort of 489 mother-son pairs from Chapaevsk, Russia, a town contaminated with these chemicals during past industrial activity. The boys were recruited at ages 8 to 9 years, and 4 years of annual follow-up data were included in the analysis. Serum samples were collected at enrollment from both mothers and sons for measurement of dioxin and PCB concentrations using high-resolution mass spectrometry. The sons' pubertal onset--defined as pubertal stage 2 or higher for genitalia (G) or pubic hair (P), or testicular volume >3 mL--was assessed annually by the same physician.
In multivariate Cox models, elevated maternal serum PCBs were associated with earlier pubertal onset defined by stage G2 or higher (4th quartile hazard ratio = 1.7 [95% confidence interval = 1.1- 2.5]), but not for stage P2 or higher or for testicular volume >3 mL. Maternal serum concentrations of dioxin toxic equivalents were not consistently associated with the sons' pubertal onset, although a dose-related delay in pubertal onset (only for G2 or higher) was seen among boys who breast-fed for 6 months or more.
Maternal PCB serum concentrations measured 8 or 9 years after sons' births--which may reflect sons' prenatal and early-life exposures--were associated with acceleration in some, but not all, measures of pubertal onset.
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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.
We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region.
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.
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.
Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation.
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Exposures to endocrine-disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters.
We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men.
From 2003 through 2005, 516 boys were enrolled at age 8-9 years and followed for up to 10 years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At 18-19 years, 133 young men provided 1 or 2 semen samples (256 samples) collected approximately 1 week apart, which were analyzed for volume, sperm concentration, and motility. Unadjusted and adjusted linear mixed models were used to examine the associations of quartiles of lipid-standardized concentrations of dioxins [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated dibenzo-p-dioxins (PCDDs)], furans, polychlorinated biphenyls (PCBs), and corresponding toxic equivalents (TEQs) with semen parameters.
The median (range) for TCDD was 2.9 (0.4-12.1) pg/g lipid and PCDD TEQ was 8.7 (1.0-36.0) pg TEQ/g lipid. Higher quartiles of TCDD and PCDD TEQs were associated with lower sperm concentration, total sperm count, and total motile sperm count (p-trends = 0.05). The highest quartile of peripubertal serum TCDD concentrations was associated with a decrease (95% CI) of 40% (18, 66%), 29% (3, 64%), and 30% (2, 70%) in sperm concentration, total sperm count, and total motile sperm count, respectively, compared with the lowest quartile. Similar associations were observed for serum PCDD TEQs with semen parameters. Serum PCBs, furans, and total TEQs were not associated with semen parameters.
Higher peripubertal serum TCDD concentrations and PCDD TEQs were associated with poorer semen parameters. Citation: M?nguez-Alarc?n L, Sergeyev O, Burns JS, Williams PL, Lee MM, Korrick SA, Smigulina L, Revich B, Hauser R. 2017. A longitudinal study of peripubertal serum organochlorine concentrations and semen parameters in young men: the Russian Children's Study. Environ Health Perspect 125:460-466; http://dx.doi.org/10.1289/EHP25.
Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Electronic address: firstname.lastname@example.org.
Childhood blood lead levels (BLL) have been associated with growth impairment.
We assessed associations of peripubertal BLL with adolescent growth and near adult height in a longitudinal cohort of Russian boys.
481 boys were enrolled at ages 8-9years and followed annually to age 18. At enrollment, BLL was measured, and height, weight, and pubertal staging were obtained annually during 10years of follow-up. Mixed effects models were used to assess the associations of BLL with longitudinal age-adjusted World Health OrganizationZ-scores for height (HT-Z) and body mass index (BMI-Z), and annual height velocity (HV). Interactions between boys' age and BLL on growth outcomes were evaluated.
The median (range) BLL was 3.0 (0.5-31.0) µg/dL. At age 18years, 79% of boys had achieved near adult height (HV
Cites: Environ Health. 2015 Dec 30;14:95 PMID 26715556
Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals.
Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p?-DDE)-among boys in Chapaevsk, Russia.
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 ?-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, ?-HCH, and p,p?-DDE concentrations.
Among 355 boys with OCP measurements, median serum HCB, ?-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 3 years in Chapaevsk predicted higher ?-HCH concentrations, and having parents who lacked a high school education predicted higher p,p?-DDE concentrations.
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.
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