Grantee Research Project Results
2007 Progress Report: Dioxins, Male Pubertal Development and Testis Function
EPA Grant Number: R829437Title: Dioxins, Male Pubertal Development and Testis Function
Investigators: Hauser, Russ
Current 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 Period Covered by this Report: December 1, 2006 through November 30,2007
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:
Chapaevsk is a small city in southwestern Russia that has environmental contamination with polychlorinated dibenzodioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs). The primary aim of the Chapaevsk Boys Study is to examine the effects of PCDD/F/PCBs on physical growth and sexual maturation. Initially, we examined the predictors of serum total toxic equivalents of PCDD/F/PCBs (TEQs).
Progress Summary:
The Chapaevsk Boys Study is a prospective cohort of 499 peri-pubertal boys, enrolled at ages 8 and 9 years of age during 2003 through 2005. The present analysis considers 123 boys with serum TEQ analyses. The boys’ initial study visit included physical exams, blood sampling, completion of health history, dietary, and mood questionnaires. The blood samples were analyzed for PCDD/F/PCBs by the Centers for Disease Control and Prevention (CDC). TEQs were calculated for PCDD/F/PCBs using both the WHO 1998 and 2005 toxic equivalent factors (TEFs). General linear regression models, using a log10-transformation of the serum total TEQs, were used to assess associations with covariates, such as maximal parental education, number of siblings (none or one vs. two or more), body mass index (BMI; kg/m2), obesity (>= 22.77 BMI), duration of breast feeding (weeks), and consumption of local foods (any vs. none, except fruit and vegetables in quintiles. Local food consumption was adjusted for total food consumption, and modeled by each separate food category (eggs, poultry, fruit and vegetables, meat, fish, dairy).
Results:
The mean (95% CI) 1998 and 2005 TEQs, respectively, for total PCDD/PCDF/PCBs were 47.7 (42.1, 53.3) and 33.7 (29.5, 37.8). The 1998 TEQs were composed of 26% PCDDs, 20% PCDFs, 23% co-planar PCBs, and 31% mono-ortho PCBs. The 2005 TEQs were composed of 37% PCDDs, 20% PCDFs, 36% co-planar PCBs, and 9% mono-ortho PCBs. In multivariate models, significant predictors of the 2005 serum total TEQs were duration of breast feeding, number of siblings, consumption of local eggs, local poultry, local fruits and vegetables, obesity, BMI, and parental education. Breast feeding for 17 weeks (the median) was associated with an increase of 1.12 TEQs (95% CI: 1.06, 1.18) as compared with no breast feeding. Higher serum total TEQs were also associated with two or more siblings (1.47 TEQs; 95% CI 1.03, 2.11) compared with one or no siblings, local egg consumption (1.61TEQs; 95% CI 1.27, 2.05) compared with no local egg consumption, local poultry consumption (1.70 TEQs; 95% CI 1.09, 2.66) compared with no local poultry consumption, the highest quintile of local fruit and vegetable consumption (2.06 TEQs; 95% CI 1.35, 3.13) compared with the lowest quintile, and obesity (2.35 TEQs; 95% CI 0.94, 2.52) compared with normal weight. Higher BMI and higher parental education were associated with lower serum total TEQs. The results were similar using the WHO 1998 TEQs.
Conclusions:
The serum total TEQs were much lower using the WHO 2005 standards, as expected, primarily due to the reduction in the TEFs for mono-ortho PCBs. However, the associations with predictors remained consistent across both WHO TEQs. The expected associations were found between duration of breast feeding, parental education, and consumption of local foods with higher serum total TEQs. However, the finding of a negative association of BMI with serum total TEQs while there was a positive association of obesity with serum total TEQs is unexpected, and requires further investigation which will be possible when the full complement of study data are available. This suggests that adiposity may have a complex relationship with serum PCDD/F/PCBs.
Summary statistics for dioxin and PCB summary values after adjustment for measures below the LOD, using LOD/sqrt(2 )N=501 boys. We only received these results recently so further analyses are pending.
Distribution of concentrations of PCDDs/PCDFs/Co-planar PCBs (pg/g lipid) Adjustment for below the limit of detection (LOD/sqrt(2))
|
||||||||
|
N
|
Mean
|
SD
|
Min
|
25th%
|
Median
|
75th%
|
Max
|
2378-TCDDs
|
482
|
3.1
|
3.1
|
0.3
|
1.3
|
2.8
|
3.9
|
44.9
|
Total PCDDs
|
482
|
159.2
|
109.1
|
23.4
|
93.3
|
135.5
|
189.0
|
1237.2
|
Total PCDFs
|
482
|
56.8
|
77.1
|
4.6
|
26.7
|
38.9
|
57.3
|
1083.3
|
Total Co-PCBs
|
482
|
209.5
|
143.7
|
56.6
|
126.2
|
180.9
|
249.1
|
2067.4
|
Total M-PCBs
|
477
|
69.8
|
85.6
|
12.6
|
35.3
|
51.7
|
78.2
|
1560.1
|
Total PCDD/F/C-PCBs
|
482
|
425.4
|
247.3
|
123.3
|
278.0
|
362.3
|
498.9
|
2962.8
|
Total PCBs (ng/g lipids)
|
477
|
331.0
|
310.6
|
62.3
|
163.6
|
249.4
|
392.7
|
4248.1
|
Distribution of 2005 TEQs (pg/g lipid) Adjustment for below the limit of detection (LOD/sqrt(2))
|
||||||||
|
N
|
Mean
|
SD
|
Min
|
25th%
|
Median
|
75th%
|
Max
|
2378-TCDDs
|
482
|
3.1
|
3.1
|
0.3
|
1.3
|
2.8
|
3.9
|
44.9
|
Total PCDDs
|
482
|
10.5
|
9.5
|
0.9
|
4.5
|
8.2
|
13.5
|
89.8
|
Total PCDFs
|
482
|
6.9
|
11.1
|
0.4
|
3.0
|
4.2
|
6.9
|
154.3
|
Total Co-PCBs
|
482
|
8.1
|
6.6
|
0.5
|
4.5
|
6.4
|
9.4
|
67.2
|
Total M-PCBs
|
477
|
2.1
|
2.6
|
0.4
|
1.1
|
1.6
|
2.4
|
46.8
|
Total PCDD/F/PCBs
|
477
|
27.6
|
21.9
|
4.0
|
14.4
|
21.1
|
33.2
|
174.7
|
Significance
The present study represents a unique opportunity to study the impact of environmental chemicals on growth and pubertal development. We will explore several hypotheses on the relationship of dioxin exposure with growth and adiposity, as well as with onset and tempo of sexual development. To date our publications have focused on exposure characterization. In addition, we have published on lead and pubertal development. We focused first on lead because the dioxin results were delayed. We recently received them and included tables delineating serum levels among the boys. Because the study is a longitudinal study, it will take several years to gather the data necessary to fully explore the timing and tempo of pubertal development.
Future Activities:
During the coming year, annual follow-up on the boys will continue. We added procedures to measure percent body fat using a bioelectric impedance unit. We also plan to measure serum levels of micronutrients to better understand the nutritional intake of the boys. The annual follow-up visit includes a urine sample and update of the medical, lifestyle and diet history, and a blood sample bi-annually.
Journal Articles on this Report : 5 Displayed | Download in RIS Format
Other project views: | All 11 publications | 9 publications in selected types | All 9 journal articles |
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Type | Citation | ||
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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 |
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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) |
Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit |
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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 |
Supplemental Keywords:
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, neurotropin growth, male sexual development, dioxin, puberty, cell-cell interactions, testis development, EDCs, endocrine disrupting chemicals, sexual development, sertoli cells, developmental biology, hypospadias, human growth and development, physiology, fetal development, human exposure, chemical interference, embryonic development, gonad morphology, testis function, postnatal development, paracine growth factors, male fertilityProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2006 Progress Report
- 2005 Progress Report
- 2004 Progress Report
- 2003 Progress Report
- 2002 Progress Report
- Original Abstract
9 journal articles for this project