RESUMEN
BACKGROUND: The etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs). OBJECTIVE: To evaluate the association between perinatal exposure to 27 potential EDCs and ASD among Norwegian children, and to further examine the neurodevelopmental toxicity of associated chemicals using zebrafish embryos and larvae. METHOD: 1,199 mothers enrolled in the prospective birth-cohort (HUMIS, 2002-2009) study. Breastmilk levels of 27 chemicals were measured: polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances as a proxy for perinatal exposure. We employed multivariable logistic regression to determine association, utilized elastic net logistic regression as variable selection method, and conducted an in vivo study with zebrafish larvae to confirm the neurodevelopmental effect. RESULTS: A total of 20 children had specialist confirmed diagnosis of autism among 1,199 mother-child pairs in this study. ß-Hexachlorocyclohexane (ß-HCH) was the only chemical associated with ASD, after adjusting for 26 other chemicals. Mothers with the highest levels of ß-HCH in their milk had a significant increased risk of having a child with ASD (OR = 1.82, 95 % CI: 1.20, 2.77 for an interquartile range increase in ln-transformed ß-HCH concentration). The median concentration of ß-HCH in breast milk was 4.37 ng/g lipid (interquartile range: 2.92-6.47), and the estimated daily intake (EDI) for Norwegian children through breastfeeding was 0.03 µg/kg of body weight. The neurodevelopmental and social behavioral effects of ß-HCH were established in zebrafish embryos and larvae across various concentrations, with further analysis suggesting that perturbation of dopaminergic neuron development may underlie the neurotoxicity associated with ß-HCH. CONCLUSIONS: Prenatal exposure to ß-HCH was associated with an increased risk of specialist-confirmed diagnoses of ASD among Norwegian children, and the EDI surpasses the established threshold. Zebrafish experiments confirm ß-HCH neurotoxicity, suggesting dopaminergic neuron disruption as a potential underlying mechanism.
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Trastorno del Espectro Autista , Disruptores Endocrinos , Contaminantes Ambientales , Embarazo , Femenino , Animales , Humanos , Pez Cebra , Disruptores Endocrinos/toxicidad , Estudios Prospectivos , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/epidemiología , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/análisis , Cohorte de Nacimiento , Noruega/epidemiologíaRESUMEN
Three degradation strains that can utilize ß-Hexachlorocyclohexanes (ß-HCH) as the sole carbon source were isolated from the soil substrate of constructed wetland under long-term ß-HCH stress, and they were named A1, J1, and M1. Strains A1 and M1 were identified as Ochrobactrum sp. and strain J1 was identified as Microbacterium oxydans sp. by 16S rRNA gene sequence analysis. The optimum conditions for degradation with these three strains, A1, J1, and M1, were pH = 7, 30 °C, and 5% inoculum amount, and the degradation rates of 50 µg/L ß-HCH under these conditions were 58.33%, 51.96%, and 50.28%, respectively. Degradation characteristics experiments showed that root exudates could increase the degradation effects of A1 and M1 on ß-HCH by 6.95% and 5.82%, respectively. In addition, the degradation bacteria A1 and J1 mixed in a ratio of 1:1 had the highest degradation rate of ß-HCH, which was 69.57%. An experiment on simulated soil remediation showed that the compound bacteria AJ had the best effect on promoting the degradation of ß-HCH in soil within 98 d, and the degradation rate of ß-HCH in soil without root exudates was 60.22%, whereas it reached 75.02% in the presence of root exudates. The addition of degradation bacteria or degradation bacteria-root exudates during soil remediation led to dramatic changes in the community structure of the soil microorganisms, as well as a significant increase in the proportion of aerobic and Gram-negative bacterial groups. This study can enrich the resources of ß-HCH degrading strains and provided a theoretical basis for the on-site engineering treatment of ß-HCH contamination.
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Hexaclorociclohexano , Contaminantes del Suelo , ARN Ribosómico 16S/genética , Bacterias , Suelo , Biodegradación Ambiental , Contaminantes del Suelo/análisis , Microbiología del SueloRESUMEN
Hexachlorocyclohexanes (HCHs) are widespread and persistent environmental pollutants, which cause heavy contamination in soil, sediment and groundwater. An anaerobic consortium, which was enriched on ß-HCH using a soil sample from a contaminated area of a former pesticide factory, was capable to transform α, ß, γ, and δ-HCH via tetrachlorocyclohexene isomers stoichiometrically to benzene and chlorobenzene. The carbon and chlorine isotope enrichment factors (εC and εCl) of the dehalogenation of the four isomers ranged from -1.9 ± 0.3 to -6.4 ± 0.7 and from -1.6 ± 0.2 to -3.2 ± 0.6, respectively, and the correlation of δ37Cl and δ13C (Λ values) of the four isomers ranged from 1.1 ± 0.1 to 2.4 ± 0.2. The evaluation of Λ and the apparent kinetic isotope effects (AKIE) for carbon and chlorine may lead to the hypothesis that the two eliminated chlorine atoms of α- and γ-HCH were in axial positions, the same as for the ß-HCH conformer which has six chlorine atoms in axial positions after ring flip. The dichloroelimination of δ-HCH resulted in distinct AKIE and Λ values as one chlorine atom is in axial whereas the other chlorine atoms are in the equatorial positions. Significant chlorine and carbon isotope fractionations of HCH isomers were observed in the samples from a contaminated aquifer (Bitterfeld, Germany). The 37Cl/35Cl and 13C/12C isotope fractionation patterns of HCH isomers from laboratory experiments were used diagnostically in a model to characterize microbial dichloroelimination in the field study. The comparison of isotope fractionation patterns indicates that the transformation of HCH isomers at the field was mainly governed by microbial dichloroelimination transformation.
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Cloro , Agua Subterránea , Anaerobiosis , Biodegradación Ambiental , Isótopos de Carbono/análisis , Alemania , HexaclorociclohexanoRESUMEN
Pesticides belong to a group of xenobiotics harmful to humans and wildlife, whose fate and activity depends on their susceptibility to degradation. Therefore, the monitoring of their residue level in agricultural soils is very important because it provides very valuable information on the actual level of soil contamination and environmental risk resulting from their application. The aim of this study was to evaluate contemporary concentrations of organochlorine (OCPs) and non-chlorinated pesticides (NCPs) in arable soils of Poland as an example of Central and Eastern European countries. The results were assessed in relation to Polish regulations, which are more restrictive compared to those of other European countries. The sampling area covered the territory of arable lands in Poland (216 sampling points). The distribution of sampling points aimed to reflect different geographical districts, conditions of agricultural production, and various soil properties. The collected soil samples were extracted with organic solvents in an accelerated solvent extractor (ASE 2000). The OCPs, including α-HCH, ß-HCH, γ-HCH, and p,p'DDT, p,p'DDE, and p,p'DDD, were extracted with a hexane/acetone mixture (70:30 v/v) and determined by gas chromatography with an electron capture detector (GC-µECD). NCPs included atrazine, carbaryl, and carbofuran were extracted with a dichloromethane/acetone mixture (50:50 v/v), while maneb was extracted by intensive shaking the sample with acetone (1:1 v/v) and ethylenediamine-tertraacetic acid. The NCPs were identified by a dual mass- spectrometry (GC-MS/MS). The total content of individual OCPs ranged from 0.61 to 1031.64 µg kg-1, while the NCP concentrations were significantly lower, from 0.01 to 43.92 µg kg-1. DDTs were detected in all soils samples (p,p'DDD (23.60 µg kg-1) > p,p'DDT (18.23 µg kg-1) > p,p'DDE (4.06 µg kg-1), while HCHs were only in 4% of the analyzed samples (ß-HCH (339.55 µg kg-1) > α-HCH (96.96 µg kg-1) > γ-HCH (3.04 µg kg-1)), but in higher values than DDTs. Among NCPs, higher concentration was observed for carbaryl (<0.01-28.07 µg kg-1) and atrazine (<0.01-15.85 µg kg-1), while the lower for carbofuran (<0.01-0.54 µg kg-1). Maneb was not detected in analyzed soils. Assessment of the level of soil pollution based on Polish regulations indicated that several percentages of the samples exceeded the criterion for OCPs, such as ∑3DDTs (14 samples; 6.5% of soils) and HCH congeners (α-HCH in one sample; 0.5% of soils), while NCP concentration, such as for atrazine, carbaryl and carbofuran were below the permissible levels or were not detected in the analyzed soils, e.g. maneb. The obtained results indicated that residues of the analyzed pesticides originate from historical agricultural deposition and potentially do not pose a direct threat to human and animal health. The behavior and persistence of pesticides in the soils depend on their properties. Significantly lower NCP concentration in the soils resulted from their lower hydrophobicity and higher susceptibility to leaching into the soil profile. OCPs are characterized by a high half-life time, which affect their significantly higher persistence in soils resulting from affinity to the soil organic phase.
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Agricultura , Residuos de Plaguicidas/análisis , Suelo/química , Monitoreo del AmbienteRESUMEN
BACKGROUND: Hexachlorocyclohexane is a synthetic chemical with several isomers, including ß-Hexachlorocyclohexane (ß-HCH). In 2005, a large contamination of crude milk from some bovine farms along the Sacco River (Central Italy) was detected; it was related to the illegal disposal of large quantities of processing waste by a chemical industry of the area. A biomonitoring study, conducted in 2007 on a sample of the residing population, found high values of ß-HCH in people living close to the river. These results led to the establishment of a clinical and epidemiological surveillance program on all the exposed population. The aim of the study was to evaluate the determinants of ß-HCH blood levels in people living within 1 Km of the Sacco River, focusing on the role of specific foods, body mass index and risk factors not yet identified. METHODS: The program involved all people living within 1 km of the river. A descriptive analysis of ß-HCH blood levels was done in relation to the potential determinants including specific foods. Regression analysis was used to study the association between potential determinants and (natural log) ß-HCH haematic concentration. The results were expressed as geometric mean ratios (GMR). To take into account similarities within the families we adjusted for family clustering. RESULTS: A total of 602 subjects (87.2%) agreed to participate in the surveillance. The ß-HCH geometric mean serum concentration was 72 ng/g lipid. The regression analysis showed that being female (GMR: 1.32, 95%CI: 1.14-1.53), elderly (GMR> 70yy: 10.04, 95%CI: 6.65-15.15), obese (GMR: 1.63, 95%CI: 1.28-2.08), eating food of local/own production (GMR 1.47, 95%CI: 1.15-1.88) and using water from private wells (GMRdrink:1.47, 95%CI: 1.00-2.14 and GMRwash: 1.48, 95%CI: 1.17-1.87) were associated with higher ß-HCH values. There was inverse association with breastfeeding (GMR: 0.64, 95%CI: 0.47-0.86). The focus on specific foods showed that the most important factors were eggs and beef. CONCLUSIONS: The study indicated a greater contamination for older people, and those drinking and washing with water from private wells and consuming locally produced food, especially eggs and beef.
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Contaminantes Ambientales/sangre , Hexaclorociclohexano/sangre , Características de la Residencia , Instalaciones de Eliminación de Residuos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Industria Química , Niño , Preescolar , Femenino , Humanos , Residuos Industriales , Lactante , Recién Nacido , Italia , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Organochlorine pesticides (OCPs) were banned by the Stockholm Convention many years ago; however, they are still detected in the environment due to their high persistence, their current illegal use, and their import from countries where they have not been banned. We evaluated the serum concentrations of selected OCPs (hexachlorobenzene (HCB), ß-hexachlorocyclohexanes (ß-HCH), p,p'-dichlorodiphenyltrichloroethane (DDT) and its metabolite p,p'-dichlorodiphenyldichloroethylene (DDE) in a sample of Lebanese adults using gas chromatography coupled to an ion trap mass spectrometer detector. The mean concentrations of HCB, ß-HCH, DDT, and DDE were 7.1, 8.6, 2.1, and 18.9 ng/g of lipids, respectively, and the major contributor among the four OCPs was DDE. The OCP levels in the present study were in general lower than the values observed in several countries worldwide and their concentrations at the 95th percentile were lower than the biomonitoring equivalents (BEs) excluding any appreciable health risk. We observed an inverse association between HCB concentrations and body mass index (BMI) as well as HCB, ß-HCH, and DDE levels, and smoking habits. Milk consumption however was positively associated with an increased serum level of ß-HCH. This study, which was the first to investigate OCP serum levels in a Lebanese population, provides a baseline to which future measurements can be compared.
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DDT/análisis , Diclorodifenil Dicloroetileno/análisis , Hexaclorobenceno/análisis , Hexaclorociclohexano/análisis , Hidrocarburos Clorados/análisis , Plaguicidas/análisis , Índice de Masa Corporal , DDT/química , Diclorodifenil Dicloroetileno/química , Dieta , Monitoreo del Ambiente , Hexaclorobenceno/química , Hexaclorociclohexano/química , Humanos , Hidrocarburos Clorados/químicaRESUMEN
The use of organochlorine pesticides (OCPs) is a worldwide public health concern given that high levels of these compounds in humans and animals can lead to serious health problems. This study aimed to evaluate the levels of 15 organochlorine pesticides in the serum of 547 blood donors in the São Paulo metropolitan region (SPMR) in 2009 and to investigate factors associated with higher levels of these compounds. The OCPs were determined by gas chromatography with micro electron capture detection. Multiple ordinal logistic regression models were employed to determine the factors associated with higher levels. Only ß-HCH and p,p'-DDE had a significant number of samples above the limit of quantification. Factors associated with higher levels of ß-HCH were age within 26 to 35 years (OR = 3.1 [1.05-9.09]), age within 36 to 45 years (OR = 18.27 [6.89-48.91]), and female gender (OR = 0.44 [0.24-0.82] for men). p,p'-DDE levels were associated with age within 26 to 35 years (OR = 2.65 [1.20-3.45]), age within 36 to 45 years (OR = 4.59 [2.64-7.92]), female gender (OR = 0.86 [0.43-0.94] for men), and previous work with pesticides (OR = 2.88 [1.22-6.84]). Lower levels of p,p'-DDE were associated with an income of 3 to 5 minimum wages (OR = 0.38 [0.19-0.75]) and with intake of foods from animal origin up to twice a week (OR = 0.15 [0.03-0.72]) and more than twice a week (OR = 0.10 [0.02-0.47]). The results of this study indicate that the study group was not exposed to high levels of OCPs.
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Donantes de Sangre/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Hidrocarburos Clorados/sangre , Plaguicidas/sangre , Animales , Brasil , Cromatografía de Gases , Diclorodifenil Dicloroetileno/análisis , Monitoreo del Ambiente , Femenino , Alimentos , Hexaclorociclohexano/sangre , Humanos , Hidrocarburos Clorados/análisis , MasculinoRESUMEN
Organochlorinated pesticides (OCPs) were measured in a representative sample of Spanish adults within the Bioambient.es project, a nationwide human biomonitoring program promoted by Spanish Ministry of Agriculture, Food and Environment. The objective of Bioambient.es is to establish reference levels of environmental pollutants in the general population. Participants were recruited in 2009-2010 during their annual medical examination at work. Serum levels of thirteen OCPs were investigated: Aldrin, endrin, dieldrin, heptachlor, heptachlor-epoxide, dichlorodiphenyldichloroethylenes (DDEs), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) The highest concentrations were observed for DDE, HCB and ß-HCH. The 95th percentile, in ng/g lipids, were: 717.7 for 4,4-DDE, 160.4 for HCB and 107.2 for ß-HCH, while concentrations of aldrin, endrin, heptachlor, α-HCH, 2,4-DDT, 4,4-DDT and 2,4-DDE were markedly lower and detected in less than 10% of the samples. Significant differences (p<0.05) were found for DDE and HCB and seasonality, gender and age. Analyzing the geographical distribution, participants from the north of Spain had highest levels of HCB while those from the center of Spain had highest levels of 4,4-DDE. Comparing to earlier studies, the results indicated a sharp decline in the OCP concentrations in the Spanish population over time, and today values are in the same range or lower than those reported in similar studies worldwide, except for HCHs and HCB that presented higher levels than in other European countries and much higher than those observed in US and Canada. This study represents the first nationwide survey of exposure to OCPs in Spain and provides a background reference range for exposure to OCPs in the Spanish adult occupied population. These results will allow establishing reference values, observing temporal trends and identifying high exposure groups.
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Contaminantes Ambientales/sangre , Hidrocarburos Clorados/sangre , Plaguicidas/sangre , Adulto , Monitoreo del Ambiente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , EspañaRESUMEN
The organochlorine insecticide γ-hexachlorocyclohexane (γ-HCH, lindane) and its non-insecticidal α- and ß-isomers continue to pose serious environmental and health concerns, although their use has been restricted or completely banned for decades. In this study we report the first evidence of the growth ability of a Streptomyces strain in a mineral salt medium containing high doses of α- and ß-HCH (16.6 mg l(-1)) as a carbon source. Degradation of HCH isomers by Streptomyces sp. M7 was investigated after 1, 4, and 7 days of incubation, determining chloride ion release, and residues in the supernatants by GC with µECD detection. The results show that both the α- and ß-HCH isomers were effectively metabolized by Streptomyces sp. M7, with 80 and 78 % degradation respectively, after 7 days of incubation. Moreover, pentachlorocyclohexenes and tetrachlorocyclohexenes were detected as metabolites. In addition, the formation of possible persistent compounds such as chlorobenzenes and chlorophenols were studied by GC-MS, while no phenolic compounds were detected. In conclusion, we have demonstrated for the first time that Streptomyces sp. M7 can degrade α- and ß-isomers individually or combined with γ-HCH and could be considered as a potential agent for bioremediation of environments contaminated by organochlorine isomers.
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Hexaclorociclohexano/química , Hexaclorociclohexano/metabolismo , Contaminantes del Suelo/química , Contaminantes del Suelo/metabolismo , Streptomyces/metabolismo , Anaerobiosis , Biodegradación Ambiental , Insecticidas/química , Insecticidas/metabolismo , IsomerismoRESUMEN
Due to the widespread use of agricultural and residential pesticides, the potential for pesticide soil contamination is a worldwide concern. In response, regulatory jurisdictions in at least 54 nations have promulgated guidance values to specify the maximum allowable concentration of pesticides in soils. Guidance values may be found for more than 700 pesticides. A previous analysis examined the values applied to the original "dirty dozen" persistent organic pollutant (POP) pesticides that were addressed in the 2001 Stockholm Convention (Aldrin, Chlordane, DDT, Dieldrin, Endrin, Heptachlor, Mirex, and Toxaphene). Results are presented here for the "new POP" pesticides that were added to the Stockholm Convention in 2009 and 2011 (isomers of Hexachlorocyclohexane, Chlordecone, and isomers of Endosulfan). The guidance value extremes used worldwide for these pesticides vary by as much as 8.5 orders of magnitude and the randomness in their distributions resembles that of lognormal random variables. However, there are nonrandom value clusters in some distributions that may identify values around which consensuses are forming. The current value distributions imply that a wide range of human health risks are being accepted. Hopefully, the results presented will help regulatory jurisdictions and the regulated communities identify values that should be revised to be adequately protective of human health.
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Contaminación Ambiental/prevención & control , Plaguicidas/química , Contaminantes del Suelo/química , Suelo/química , Endosulfano/química , Monitoreo del Ambiente , Hexaclorociclohexano/química , Humanos , Hidrocarburos Clorados/análisis , SueciaRESUMEN
To compare the uptake and translocation of hydrophobic organic chemicals by plant species, the authors performed uptake experiments with ß-1,2,3,4,5,6-hexachlorocyclohexane (ß-HCH) and 1,2,3,4,10,10-Hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-endo-1,4-exo-5,8-dimethanonaphthalene (dieldrin) using 5 species: Hordeum vulgare, Glycine max, Solanum lycopersicum, Brassica oleracea, and Cucurbita pepo. The present study evaluated uptake ability using root concentration factor (RCF) and translocation ability by transpiration stream concentration factor (TSCF). The RCFs of ß-HCH and dieldrin did not differ remarkably among species, except that the RCF of ß-HCH in B. oleracea was high. The TSCFs of ß-HCH and dieldrin were high in C. pepo, which was not superior in uptake as estimated by RCF. The TSCF of dieldrin in C. pepo was decreased in darkness and was markedly decreased by heating of roots. These results support the hypothesis that transport proteins produced in the root contribute to dieldrin translocation. In contrast, TSCF of ß-HCH was not decreased by these treatments. Therefore, translocation of ß-HCH might not need the contribution of transport proteins. It is possible that C. pepo has a certain function to transport hydrophobic organic chemicals smoothly in root tissues.
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Medios de Cultivo/química , Dieldrín/metabolismo , Hexaclorociclohexano/metabolismo , Hidroponía , Plantas/metabolismo , Biodegradación Ambiental , Transporte Biológico , Biomasa , Cucurbita/metabolismo , Solanum lycopersicum/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Brotes de la Planta/crecimiento & desarrollo , Transpiración de Plantas/fisiología , Glycine max/metabolismo , Factores de TiempoRESUMEN
LinB, a haloalkane dehalogenase from Sphingomonas paucimobilis UT26, is known to metabolize halohydrocarbons to halide ions and the respective alcohols. Its broad substrate specificity allowed its consideration for bioremediation. Herein, we have shown its catalytic action toward ß-hexachlorocyclohexane (ß-HCH) - an example of large-size substrates that can be accommodated in its active site. We have analyzed the capability of combined QM/MM schemes to describe in detail the SN2 dechlorination reaction between ß-HCH and Asp108 in the active site of LinB. Free energy surfaces have been calculated using one and two dimensional potentials of mean force (PMF) obtained at the PM3/MM (MM=amberff99SB, TIP3P) level of theory. The overestimated energetic barriers by the PM3 Hamiltonian were corrected using a DFT functional (M06-2X). The resulted activation energies (16 and 19 kcal mol(-1) from 1D and 2D-PMF profiles, respectively) for the dechlorination reaction of ß-HCH in the active site of LinB enzyme are in qualitative agreement with the experimentally determined value of 17 kcal mol(-1). The binding of ß-HCH to the active site of LinB has been compared to the binding of smaller 1-chlorobutane (1-CB) and larger δ-hexabromocyclododecane (δ-HBCD).
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Proteínas Bacterianas/química , Hexaclorociclohexano/química , Hidrolasas/metabolismo , Sphingomonas/enzimología , Butanos/química , Catálisis , Dominio Catalítico , Cloruros/química , Cloro/química , Biología Computacional , Hidrocarburos Bromados/química , Enlace de Hidrógeno , Hidrolasas/química , Simulación de Dinámica Molecular , Unión Proteica , Especificidad por Sustrato , Propiedades de SuperficieRESUMEN
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), ß-hexachlorocyclohexane (ß-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 ß-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.