Grantee Research Project Results

Final Report: Dioxins, Male Pubertal Development and Testis Function

EPA Grant Number: R829437
Title: Dioxins, Male Pubertal Development and Testis Function
Investigators: Hauser, Russ , Korrick, Susan A. , Williams, Paige L.
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: December 1, 2001 through November 30, 2005 (Extended to February 3, 2008)
Project Amount: $2,252,427
RFA: Endocrine Disruptors: Epidemiologic Approaches (2001) RFA Text |  Recipients Lists
Research Category: Environmental Justice , Human Health , Safer Chemicals , Endocrine Disruptors

Objective:

Specific Aim #1: To investigate whether alterations in physical growth and sexual maturation in boys are associated with in utero levels of dioxins and/or serum dioxin concentrations measured in adolescence. In utero dioxin levels will be estimated using the child’s current serum dioxin level, as well as historical reproductive (e.g. maternal breast feeding) and residential information.

Note: Described in detail of summary of results.

Specific Aim #2: To retrospectively investigate whether in utero levels of dioxins are associated with reproductive tract abnormalities, specifically hypospadias, cryptorchidism and testicular abnormalities (manifested by small testicular volume at sexual maturity).

Note: The retrospective estimation of in utero levels of dioxins is underway. A doctoral student (Olivier Humblet) is working on this aim as a main component of his thesis, with completion anticipated in the Fall of 2009. As part of this aim, in the Spring of 2009 we resampled a small subset of women from whom we now have blood samples for dioxins that are 9 years apart. This will allow us to use this data to validate our pre-natal exposure estimation models.

Specific Aim #3: To investigate whether serum dioxins measured in adolescence are associated with disturbances in testis function, specifically endocrine function and spermatogenesis.

Note: Due to the delays in funding and revision of study design (see below for details) we were unable to investigate associations of dioxins with semen quality. To assess onset of puberty in our study, by design we recruited children at age 8 to 9 years old and therefore they are currently only 14 to 15 years of age, not old enough for semen collection. We have NIEHS funding that will allow us to continue to follow these children and ultimately we will apply for NIEHS renewal funding that will allow us to assess semen quality when they reach 18 years of age

Summary/Accomplishments (Outputs/Outcomes):

The specific aims outlined in the grant proposal were modified due to difficulties in initiating a large international study in Russia. During the first year of the project, we purchased the necessary equipment and supplies, trained personnel and developed the databases that will be used through-out the study. We also experienced (and reported to EPA) very long delays in shipping the supplies to Russia, a direct result of the extensive paperwork needed for Russian customs, as well as U.S. shipping permits. It took almost a year to get the necessary approvals from the Russian government.

As originally proposed in the grant application, we were planning on following the children enrolled in our earlier pilot study (1999-2000). However, because of the delay in receiving funding (delayed from July 2001 until February 2002, due to the international scope of the project in Russia) and the delay in getting permission to send supplies to Russia, we had no choice but to assemble a new cohort of 8 and 9-year old boys rather than following the boys from the pilot study. The boys in the pilot study, as a result of the delays in the start of funding and Russian governmental delays, were too old to follow for growth and onset of sexual maturation. However, our pilot data was useful in guiding us in the optimal design of the prospective cohort study of 500 nine-year old boys. Recruitment of boys in the prospective cohort study began in May 2003.

We realized this was a change in the proposed design, but the delays were out of our control (delayed EPA funding start date – approximately 7 months) as well as unanticipated delays in procuring Russian customs approval to ship supplies (partly a result of the new post September 11^th concerns with air travel and shipping unknown supplies-approximately 8 months delay).

However, despite the delays and revision of the aims, we are still able to investigate our primary aim of the association of dioxins with alterations in physical growth and sexual maturation. The endpoints include growth velocity, onset and tempo of sexual maturation, as well attainment of sexual maturity. We believe that this change in the design of subject recruitment and follow-up was optimal and an improvement over the proposed study plan. This was discussed with Dr. David Reese in the fall and winter of 2002 and he approved our proposed changes.

Conclusions:

Between May 2003-2005, we recruited 516 boys and their families to participate in our prospective cohort study on growth and pubertal development. It is important to keep in mind that when conducting a large prospective cohort study, such as ours, it takes many years of follow-up and subsequent data analysis to generate results and publications. Although we are in year 6 of the study, we anticipate many publications and interesting results in the coming years.

1). Study participant follow-up and collection and analysis of data

Subject follow-up remains excellent and our plans include following the children until adulthood (age 18 years, so that we can assess attainment of sexual maturation and semen quality). Each year we complete annual follow-up physical examinations, urine collection and questionnaires (health, lifestyle, diet). Every other year, we collect blood from the boys. The end of year 3 follow-up was completed for all boys with an overall retention rate of 87%.

1. Dietary Analysis: We completed work with the Russian Institute of Nutrition to analyze the dietary intake information on the food frequency questionnaire. Dr. Jane Burns, a research associate on the project, has taken the lead in the dietary analysis and presented a poster at the ISEE/ISEA 2006 meeting in Paris, France.

2. Biological Samples: The analysis of dioxins, furans and PCBs by the CDC for all the baseline samples (i.e., boys and their mothers) has been completed. In addition, the baseline samples were analyzed for the organochlorine pesticides hexachlorabenze (HCB), beta-hexachlorocyclohexane (bHCCH), and dichlorodiphenyldichloroethylene (p,p'-DDE). In addition, we analyzed all baseline samples for blood lead.

In table 1, we present the results for serum PCDD/PCDF/C-PCBs (pg/g lipid) concentrations and 2005 WHO TEQs among 8-9 year old boys in the Russian Children’s Study (N=482)

Table 1.

			Concentrations b			2005 WHO TEQs (pg TEQ/g lipid) Percentiles
	Median LODa	% of samples below LOD	25th	Percentiles Median	75th	25th	Median	75th
PCDDs (pg/g lipid)
2,3,7,8-TCDD	0.60	26%	1.34	2.75	3.90	1.34	2.75	3.90
1,2,3,7,8-PeCDD	0.70	28%	1.41	4.10	7.00	1.41	4.10	7.00
1,2,3,4,7,8-HxCDD	1.10	63%	0.71	2.00	3.90	0.07	0.20	0.39
1,2,3,6,7,8-HxCDD	1.10	12%	5.40	8.70	16.6	0.54	0.87	1.66
1,2,3,7,8,9-HxCDD	1.10	52%	0.85	2.61	4.60	0.09	0.26	0.46
1,2,3,4,6,7,8-HpCDD	1.20	<1%	8.20	12.2	19.5	0.08	0.12	0.20
OCDD	16.1	26%	69.0	96.1	134	0.02	0.03	0.04
PCDFs (pg/g lipid)
2,3,7,8-TCDF	0.70	91%	0.42	0.50	1.63	0.04	0.05	0.16
1,2,3,7,8-PeCDF	0.70	83%	0.42	0.57	1.91	0.01	0.02	0.06
2,3,4,7,8-PeCDF	0.60	3%	6.20	9.0	14.6	1.86	2.70	4.38
1,2,3,4,7,8-HxCDF	0.70	2%	4.10	6.65	12.5	0.41	0.67	1.25
1,2,3,6,7,8-HxCDF	0.70	11%	2.90	4.20	6.70	0.29	0.42	0.67
1,2,3,7,8,9-HxCDF	0.80	99%	0.42	0.57	1.41	0.04	0.06	0.14
2,3,4,6,7,8-HxCDF	0.70	88%	0.42	0.57	1.84	0.04	0.06	0.18
1,2,3,4,6,7,8-HpCDF	0.80	7%	5.47	7.50	11.3	0.06	0.08	0.11
1,2,3,4,7,8,9-HpCDF	0.80	85%	0.50	0.64	2.26	0.01	0.01	0.02
OCDF	0.90	26%	1.80	2.90	5.00	0.001	0.001	0.002
Co-planar PCBs (pg/g lipid)
3,3',4,4'-TCB 77	1.40	0%	48.9	88.1	134	0.005	0.009	0.01
3,4,4′,5-TCB 81	1.50	3%	5.90	8.45	12.6	0.002	0.003	0.004
3,3′,4,4′,5-PeCB 126	1.50	<1%	40.3	58.0	84.4	4.03	5.80	8.44
3,3′,4,4′,5,5′-HxCB 1	1.30	2%	11.1	16.9	28.9	0.33	0.51	0.87
Mono-ortho PCBs (ng/g lipid)
2,3,3′,4,4′-PeCB (105)	0.30	<1%	4.90	7.40	11.1	0.15	0.22	0.33
2,3′,4,4′,5-PeCB (118)	0.30	<1%	22.4	33.1	48.7	0.67	0.99	1.46
2,3,3′4,4′,5-HxCB (156)	0.40	1%	3.60	5.80	10.7	0.11	0.17	0.32
2,3,3′,4,4′,5′-HxCB (157)	0.40	14%	1.00	1.80	3.30	0.03	0.05	0.10
2,3′,4,4′,5,5′-HxCB (167)	0.50	11%	1.30	2.10	3.45	0.04	0.06	0.10
2,3,3′,4,4′,5,5′-HpCB (189)	0.60	73%	0.21	0.57	0.78	0.006	0.02	0.02
Total PCDDs (pg/g lipid)			93.3	136	189	4.5	8.2	13.5
Total PCDFs (pg/g lipid)			26.7	38.9	57.3	3.0	4.2	6.9
Total co-planar PCBs (pg/g lipid)			126	181	249	4.5	6.4	9.4
Total PCDD/F/Co-planar PCBs (pg/g lipid)			278	362	499	13.3	19.6	30.5
Total Mono-ortho PCBs (ng/g lipid)			35.3	51.7	78.2	1.1	1.6	2.4
Total PCBs (ng/g lipid)			164	249	393
Total TEQs						14.4	21.1	33.2

^aMedian LOD (limit of detection): median of sample specific LOD for each congener;
^bSamples below the LOD were assigned a value = LOD/√2;
Congeners are identified according to the International Union for Pure and Applied Chemistry (IUPAC) nomenclature.

1. Manuscript, ‘Association of blood lead levels with onset of puberty in Russian boys’. Russ Hauser, Oleg Sergeyev, Susan Korrick, Mary M. Lee, Boris Revich, Elena Gitin, Jane Burns, Paige Williams was published in Environmental Health Perspectives 2008 Jul;116(7):976-80.

Background: Epidemiological studies suggest a temporal trend of earlier onset and longer duration of puberty, raising concerns regarding the potential impact of environmental factors on pubertal development. Lead exposure has been associated with delayed pubertal onset in girls; however, epidemiologic data in boys is limited.

Methods: We used multivariable logistic regression models to explore the cross-sectional association of blood lead levels with growth and pubertal onset based on physician-assessed testicular volume and pubertal staging in 489 eight- to nine-year old boys from Chapaevsk, Russia. Multivariable linear regression models were used to assess associations of blood lead levels with somatic growth at the study entry visit.

Results: The median (25^th, 75^th percentile) blood lead level was 3 µg/dL (2 µg/dL, 5 µg/dL). Height, weight, BMI, birth weight and gestational age were predictive of the onset of puberty as assessed either by testicular volume (greater than 3 ml), Genitalia Stage (G2), or both. Blood lead level was inversely associated with height (P< 0.001) and weight (P=0.06) after adjustment for birth weight, gestational age, and age at examination. In multivariable adjusted analyses, boys with blood lead levels of 5 µg/dL or higher had a 43% reduced odds of having entered G2 as compared to those with lower levels (OR=0.57; 95% CI: 0.34-0.95, p=0.03).

Conclusions: Relatively low environmental blood lead levels were associated with decreased growth and differences in pubertal onset in peri-adolescent Russian boys. Future analyses of this prospective cohort will address pubertal onset and progression in relation to lead and other environmental chemicals.

Table. Association of lead (natural log transformation) with measures of physical growth and birth characteristics among 8- to 9-year-old Russian boys (n=489) based on univariate and multiple linear regression models.

	Unadjusted Regression Coefficient			Adjusted Regression Coefficient**
	Estimate	95% CI	P-value	Estimate	95% CI	p-value
Height (cm)	-1.043	(-1.95,-0.13)	0.02	-1.439	(-2.25,-0.63)	<0.001
Weight (kg)	-0.764	(-1.57,0.04)	0.06	-0.761	(-1.54,0.02)	0.067
Body Mass Index	-0.206	(-0.54,0.13)	0.22	-0.107	(-0.44,0.23)	0.53
Penile Length (cm)	-0.004	(-0.11,0.10)	0.94	0.023	(-0.09,0.13)	0.68
Birth Weight (kg)	-0.094	(-0.17,-0.02)	0.02	-0.084	(-0.15,-0.02)	0.01
Gestational Age (wks)	-0.038	(-0.29,0.22)	0.77	0.118	(-0.09,0.33)	0.27

** - linear regression models adjusted for birthweight, gestational age, and age at exam (except for models for birthweight and gestational age, which are adjusted for all other listed effects)

Table. Odd ratios for the association of lead (natural log transformation and high lead) with puberty onset among 8- to 9-year-old Russian boys (n=489) based on logistic regression models.

	Unadjusted regression coefficient			Adjusted regression coefficient**
	OR	95% CI	p-value	OR	95% CI	p-value
Models for effect of Lead (natural log transformation) with puberty onset
Testicular Volume
All 6 levels*	0.80	(0.61-1.06)	0.12	0.90	(0.67-1.20)	0.47
Puberty Onset (volume > 3ml)	1.01	(0.67-1.53)	0.96	1.08	(0.69-1.70)	0.74
Tanner Staging
Tanner Stage ≥ G2	0.82	(0.60-1.12)	0.20	0.75	(0.53-1.06)	0.10
Tanner Stage ≥ P2	1.37	(0.81-2.33)	0.24	1.08	(0.60-1.93)	0.81
Models for effect of High Lead (5 μg/dL or higher) with puberty onset
Testicular Volume
All 6 levels*	0.57	(0.39-0.83)	0.004	0.72	(0.48-1.07)	0.11
Puberty Onset (volume > 3ml)	0.77	(0.42-1.40)	0.39	0.83	(0.43-1.59)	0.58
Tanner Staging
Tanner Stage ≥ G2	0.58	(0.36-0.92)	0.02	0.57	(0.34-0.95)	0.03
Tanner Stage ≥ P2	0.90	(0.44-1.85)	0.78	0.74	(0.34-1.60)	0.44

Abbreviations: OR=odds ratio; 95% CI= 95% confidence interval

* - based on ordinal logistic regression model under proportional odds assumption

** - adjusted for birth weight, gestational age, height, body mass index, and age at examination

2. Manuscript, ‘Predictors of serum dioxins and PCBs among peri-pubertal Russian boys’. Jane S. Burns, Paige L. Williams, Oleg Sergeyev, Susan Korrick, Mary M. Lee, Boris Revich, Larisa Altshul, Donald G. Patterson Jr., Wayman E. Turner, Igor Saharov, Russ Hauser was published in Environmental Health Perspectives (In Press)

Background: Although sources and routes of exposure to dioxins and dioxin-like compounds have been studied, there is limited information regarding exposure among children. Breast-feeding and diet are two important contributors to early life exposure. To further understand important contributors to childhood exposure, we studied a cohort of children from a city with documented high environmental dioxin levels.

Objectives: To investigate predictors of serum concentrations of PCDD/PCDF/Co-planar PCBs (C-PCBs), toxic equivalents (TEQs), and PCBs among peri-pubertal boys in Chapaevsk, Russia.

Methods: General linear regression models were used to explore associations of log₁₀-transformed serum concentrations of PCDD/PCDF/C-PCBs, TEQs, and PCBs at study entry with anthropometric, demographic, geographic, and dietary factors in 482 boys aged 8-9 years in Chapaevsk, Russia.

Results: The median (25^th, 75^th percentile) concentration for 2005 total TEQs was 21.1 pg WHO/g lipid (14.4, 33.2). Boys who were older, consumed local foods, had longer duration of breast feeding, and whose mothers were employed at the Khimprom chemical plant or gardened locally had significantly higher serum dioxins and PCBs, while boys with higher BMI or more educated parents had significantly lower serum dioxins and PCBs. Boys who lived < 2 km from Khimprom had higher total TEQs (adjusted mean=30.6; 95% CI 26.8, 35.) than boys who lived > 5 km away (adjusted mean=18.8; 95% CI 17.2, 20.6).

Conclusions: Our findings suggest that there are unique local sources of exposure to dioxins and PCBs among children in Chapaevsk including maternal gardening, consumption of locally grown food, and residential proximity to Khimprom.

Table. Predictors of log total 2005 TEQs (PCDD/PCDF/C-PCB/M-PCBs) (pg/g lipid) among 8-9 year old boys in the Russian Children’s Study

		Adjusted Regression Coefficienta,b
Predictor	Estimate	95% CI	P-value
Age (years)	0.102	(0.057, 0.147)	< 0.0001
Body mass index (kg/m2)	-0.032	(-0.042, -0.023)	< 0.0001
Duration of breast feeding (weeks)	0.002	(0.002, 0.003)	< 0.0001
Maximum parental educationc	-0.034	(-0.072, 0.004)	0.08
Residence in Chapaevsk (years)	0.008	(0.001, 0.016)	0.03
Mother’s ever employed at Khimprom	0.112	(0.016, 0.209)	0.02
Mother’s local gardening	0.091	(0.045, 0.137)	< 0.0001
Current residence, distance from Khimprom
< 2 km	0.212	(0.141, 0.282)	< 0.0001
2-5 km	0.072	(0.022, 0.122)	0.005
>5 km		Reference
Any local eggs eaten	0.215	(0.158, 0.271)	< 0.0001
Any local non-poultry meat eaten	0.150	(0.056, 0.244)	0.002
Any local poultry eaten	0.143	(0.060, 0.225)	0.001
Any local dairy eaten	0.085	(0.038, 0.131)	< 0.0001
Any local fish eaten	0.076	(0.020, 0.133)	0.008
Highest category of local
fruit/vegetable eatend	0.140	(0.021, 0.259)	0.02

^aAdjusted for age, BMI, breast feeding, parental education, residence in Chapaevsk, mother’s employment at Khimprom, mother’s local gardening, residential distance from Khimprom;
^bLocal foods separately included in multivariate model, adjusted for total consumption;
^cOrdinal: reference level=secondary education or less, with higher levels of junior college/technical training and university graduate;
^dReference= lowest category of local consumption

3. Dr. Jane Burns, the research associate working on the project, was awarded an NIEHS R03 grant proposal on dioxins and dysregulation of glucose and lipid metabolism among the Russian boys. This application represents a direct extension of the parent grant originally funded by the US EPA.

R03 description and proposed aims:

Recent epidemiologic studies have reported associations of serum concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) with elevated serum glucose and insulin, and greater risk of type 2 diabetes mellitus (T2DM). Most of these studies have been cross-sectional and were unable to establish a temporal association or identify critical exposure periods between serum PCDDs and PCDFs (herein referred to as dioxins) and PCBs with these outcomes. None of these studies were conducted among children. In the last two decades, the incidence of childhood obesity and T2DM has increased substantially. Contributory factors include diet, physical activity, and genetic predisposition. Epidemiological studies suggest environmental exposures such as dioxins and PCBs may also play a role. Obesity and T2DM are associated with impaired glucose metabolism, dyslipidemia, and altered serum adipokines. Recent research suggests that alterations in these biomarkers of energy homeostasis in children may precede and promote the development of obesity and T2DM.

We propose to extend the original aims of the Russian Children’s Study to evaluate whether higher peri-pubertal serum dioxins and PCB levels are associated with dysregulation of energy homeostasis, with a specific focus on glucose, lipid, and adipocyte metabolism, and adiposity. The proposal’s prospective design will permit us to evaluate whether exposure to elevated dioxins and PCBs during the peri-pubertal period is associated with subsequent glucose dysregulation, altered fat and adipokine metabolism, and increased adiposity.

Specific Aim #1: To evaluate the associations of peri-pubertal serum dioxin and PCB concentrations with dysregulation of energy homeostasis with a specific focus on glucose, lipid, and adipocyte metabolism.

Hypothesis 1: Higher peri-pubertal serum dioxin and PCB concentrations are associated with abnormal glucose metabolism as measured by: a) higher fasting glucose; b) higher fasting insulin; c) higher fasting glucose/insulin ratio; d) higher homeostatic model assessment values for insulin resistance (HOMA-IR) with longitudinal increases in these biomarkers among children with higher serum dioxin and PCBs.

Hypothesis 2: Higher peri-pubertal serum dioxin and PCB concentrations are associated with dyslipidemia as measured by: a) higher total cholesterol; b) higher triglycerides; c) lower high density cholesterol (HDL); d) higher total cholesterol/HDL ratio with longitudinal increases in total cholesterol, triglycerides, and decreases in HDL among children with higher serum dioxins and PCBs.

Hypothesis 3: Higher peri-pubertal serum dioxin and PCB concentrations are associated with altered adipokine metabolism as measured by: a) higher leptin; b) lower adiponectin with longitudinal increases in leptin and decreases in adiponectin among children with higher serum dioxins and PCBs.

Specific Aim #2: To evaluate the associations of peri-pubertal serum dioxin and PCB concentrations with clinical measures of adiposity.

Hypothesis 4: Higher peri-pubertal serum dioxin and PCB concentrations are associated with increased body fat as measured by: a) greater waist circumference; b) higher body mass index (BMI); c) higher percent body fat using bio-electric impedance with greater increases in body fat among children with higher serum dioxins and PCBs over time.

1. Hormone analysis

Due to the shipping embargo of Russian biological samples (imposed Spring 2007), we have spent the last year identifying labs in Russia with the capacity to measure ultralow levels of hormones in prepubertal boys, in particular serum testosterone levels. We reviewed laboratory methods from several Russian labs to determine which labs had the appropriate methodologies available for hormone analysis. We also performed validation studies in which our Russian collaborators collected discarded children’s blood (ages 5 to 18 yrs) from the clinic and hospital population in Chapaevsk and Samara. They prepared duplicates and triplicates of individual and pooled blood samples (grouped by ages) to determine both the sensitivity and coefficients of variation for the laboratory assays. The validation study allowed us to identify Russian labs to perform testosterone and gonadotropin analysis on the samples from the boys enrolled in the study. Blood sample analysis will begin later this year and continue through 2009 and early 2010.

Explanation of how the research adds to our understanding of or solutions for environmental problems or is otherwise of benefit to the environment and human health.

Our research study is still ongoing but has already greatly added to our understanding of environmental contamination by dioxins, furans, PCBs and lead and their potential health effects on children. Throughout the study, we worked closely with the Chapaevsk Medical Association. Dr. Sergeyev and the Chapaevsk Medical Assocaition played a key role in the integration of scientific interests used to identify the adverse health impacts of environmental factors. They also represented interests of the Chapaevsk government to reduce the environmentally-related health risks and to improve children’s health in Chapaevsk and throughout Russia. In addition, our study is relevant to improving the health of all children since dioxin exposure is a global issue. Therefore, the results are relevant to children in the U.S.

In our research project, the applicant (Sergeyev Oleg and CMA) examined 516 boys and collected detailed family information. Boys with reproductive tract abnormalities and who needed surgery were identified and referred to Samara (regional) Children Hospital by Dr. Sergeyev who works as endocrinologist-urologist in Chapaevsk Children Polyclinic. Boys who needed conservative treatment, received this treatment by Dr. Sergeyev. All additional examination and treatment was free for families. Note that treatment was not the aim of research project.

Based on the finding of associations of dioxin serum levels and dietary intake of local food, we developed and provided dietary recommendations to limit intake of PCDDs and PCBs for each child and his mothers. These recommendations also were published in local newspaper as a separate newspaper page. Because Dr. Sergeyev is a member of Chapaevsk Eco-Club under the local newspaper, he initiated 4 meetings of the Eco-club where they discussed study findings and actions for reduction of environmentally-related health risks. These meeting were covered and highlighted in the newspaper and most of the citizens of Chapaevsk were able to read this. Therefore, our results had widespread public dissemination.

Results of all Chapaevsk studies were presented at Public Hearings in March 2007. Every year the Chapaevsk Local Government prepared documentation of regional donations using data and progress of the Chapaevsk epidemiological study. As a result of our study and its visibility in the Samara region, a Children’s Hospital was built in Chapaevsk. The grand opening of hospital was May 2009. This accomplishment is quite remarkable given that Chapaevsk is a relatively small town of 70,000 residents and the new Children’s Hospital is state of the art and will draw patients from the surrounding Samara region, home to several million residents. The decision to locate the hospital in Chapaevsk was an important accomplishment.

In addition to the tangible benefits in public health of children in Chapaevsk, the scientific results on the potential impact of dioxins and lead on growth and development of children will be useful to risk assessors and help determine levels of risk from these pervasive compounds. In the U.S. there is current interest and discussion regarding risk from lead at low levels (below 10 or 5 ug/dl). Our data will be useful for these risk assessments. In closing, it is our anticipated hope that as the study follow-up continues, we will further add to our understanding of the risks of these compounds on children’s health, ultimately improving children’s health.

Journal Articles on this Report : 9 Displayed | Download in RIS Format

Publications Views

Other project views:	All 11 publications	9 publications in selected types	All 9 journal articles

Publications

Type	Citation	Project	Document Sources
Journal Article	Burns JS, Williams PL, Sergeyev O, Korrick S, Lee MM, Revich B, Altshul L, Turner WE, Patterson DG, Saharov I, Hauser R. Predictors of serum dioxins and PCBs in a Russian cohort of boys. Organohalogen Compounds 2008;70:1490-1493.	R829437 (Final)	not available
Journal Article	Burns JS, Williams PL, Sergeyev O, Korrick S, Lee MM, Revich B, Altshul L, Patterson Jr. DG, Turner WE, Needham LL, Shararov I, Hauser R. Predictors of serum dioxins and PCBs among peripubertal Russian boys. Environmental Health Perspectives 2009;117(10):1593-1599.	R829437 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP
Journal Article	Hauser R, Williams P, Altshul L, Korrick S, Peeples L, Patterson Jr. DG, Turner WE, Lee MM, Revich B, Zeilert V, Sergeyev O. Characterization and predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia. Organohalogen Compounds 2004;66:3245-3251.	R829437 (2004) R829437 (2006) R829437 (2007) R829437 (Final)	not available
Journal Article	Hauser R, Williams P, Altshul L, Korrick S, Peeples L, Patterson DG Jr, Turner WE, Lee MM, Revich B, Sergeyev O. Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia: a cross-sectional pilot study. Environmental Health: A Global Access Science Source 2005;4(1):8.	R829437 (2004) R829437 (2006) R829437 (2007) R829437 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Environmental Health Exit Other: Environmental Health PDF Exit
Journal Article	Hauser R, Sergeyev O, Korrick S, Lee MM, Revich B, Gitin E, Burns JS, Williams PL. Association of blood lead levels with onset of puberty in Russian boys. Environmental Health Perspectives 2008;116(7):976-980.	R829437 (2007) R829437 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP Exit Abstract: EHP Exit Other: EHP PDF Exit
Journal Article	Lee MM, Sergeyev O, Williams P, Korrick S, Zeilert V, Revich B, Hauser R. Physical growth and sexual maturation of boys in Chapaevsk, Russia. Journal of Pediatric Endocrinology & Metabolism 2003;16(2):169-178.	R829437 (2003) R829437 (2006) R829437 (2007) R829437 (Final)	Abstract from PubMed Abstract: Reference Global Exit
Journal Article	Milnes MR, Bryan TA, Medina JG, Gunderson MP, Guillette Jr. LJ. Developmental alterations as a result of in ovo exposure to the pesticide metabolite p,p '-DDE in Alligator mississippiensis. General and Comparative Endocrinology 2005;144(3):257-263.	R829437 (Final) R824760 (Final)	Abstract from PubMed Full-text: Science Direct - Full Text HTML Exit
Journal Article	Sergeyev O, Revich B, Williams P, Korrick S, Zeilert V, Lee MM, Ushakova T, Saharov I, Altshul L, Hauser R. A case-cohort study of cryptorchidism, hypospadias and delayed sexual maturation in a dioxin contaminated region: Chapaevsk, Russia. Organohalogen Compounds 2002;59:385-388.	R829437 (2004) R829437 (2006) R829437 (2007) R829437 (Final)	not available
Journal Article	Williams P, Sergeyev O, Lee M, Korrick S, Burns J, Humblet O, DelPrato J, Revich B, Haer R. Blood Lead Levels and Delayed Onset of Puberty in a Longitudinal Study of Russian Boys. PEDIATRICS 2010;125(5):E1088-E1096.	R829437 (Final)	Full-text from PubMed Abstract from PubMed Full-text: Pediatrics - Full Text HTML Exit Other: Pediatrics - Full Text PDF Exit

Supplemental Keywords:

Children, Dioxins, Health, Human, Lead, Puberty,, RFA, Health, Scientific Discipline, Toxics, Health Risk Assessment, pesticides, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Risk Assessments, Biochemistry, Children's Health, Molecular Biology/Genetics, Biology, Endocrine Disruptors - Human Health, puberty, dioxin, neurotropin growth, male sexual development, cell-cell interactions, testis development, EDCs, endocrine disrupting chemicals, sexual development, sertoli cells, developmental biology, hypospadias, human exposure, human growth and development, physiology, fetal development, chemical interference, embryonic development, gonad morphology, testis function, human health risk, postnatal development, paracine growth factors

Progress and Final Reports:

Original Abstract

2002 Progress Report

2003 Progress Report

2004 Progress Report

2005 Progress Report

2006 Progress Report

2007 Progress Report