Grantee Research Project Results
2006 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, 2005 through November 30,2006
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
Progress Summary:
1) Progress to date: work status and progress.
Between May 2003-2005, we recruited 516 boys and their families to participate in our prospective cohort study on growth and pubertal development. The following activities are ongoing or have been accomplished during the last year:
- Follow-up: We completed annual follow-up physical examinations, urine collection and questionnaires (health, lifestyle, diet). Every other year, we collect blood from the boys. There is over a 90% retention rate per year.
- Dietary Analysis: We have begun to work with the Russian Institute of Nutrition to analyze the dietary information on the food frequency questionnaire. Dr. Jane Burns, a post-doctoral fellow, is taking the lead in the dietary analysis and presented a poster at the ISEE/ISEA 2006 meeting in Paris, France.
- Biological Samples: Blood samples from the baseline visit for boys and mothers were shipped to the CDC for analysis of dioxins, furans and PCBs. In addition, all baseline blood samples from the boys were analyzed for lead and we have a manuscript under review.
The analysis of dioxins, furans and PCBs by the CDC has been delayed for over 8 months due to equipment failures and having to postpone the Russian sample analysis until the latest round of NHANES analysis was finished. Therefore, we still do not have all the baseline samples analyzed for dioxins and PCBs.
2) Change in key personnel involved in project
Dr. Jane Burns remains as a post-doctoral fellow. She is currently supported on an environmental epidemiology training grant. Elena Gitin was added as a programmer to assist Dr. Williams with data clean-up and analysis.
3) Discussion of expenditures to date
We have requested a carry-over of funds from the present grant proposal into year 6 (no-cost extension). These funds will be used for the dioxin analysis to be carried out the CDC. We were successful in securing additional funding to continue follow-up of the boys. We received NIEHS funding for an additional 5 years. The NIEHS funding will be used for personnel, whereas the remaining EPA funds will be used to complete sample analysis as written into the original EPA budget. Therefore, there is no overlap of the use of the funds for personnel support.
4) Quality assurance
Data quality assurance continues to be maintained through a well-tested database and data entry instructional system. Dr. Hauser’s staff completed advanced courses in Access and developed and tested the database with the Russian collaborators under the direction of Dr. Sergeyev. The incorporation of this database will ensure quality control of data collection. A research assistant (created the database) and computer programmer work together to perform data clean-up and data management of the electronic databases. The research assistant interfaces directly with Dr. Sergeyev.
5) Results to date
- We published a manuscript on the results of the analysis of 30 blood samples from our pilot study for dioxins, furans, and PCBs. Predictors of dioxin levels in the children consisted of distance to Khimprom plants, dietary intake of locally raised animals (goat, chicken, etc) and locally caught fish. Table 1 highlights the important predictors (please see manuscript in attachment).
Table 1. Individual predictors of log sum of dioxinsa, adjusted for age in years (n=30 boys)
Predictor
|
Estimate
|
p-value
|
Multiplicative factor on dioxin (95% CI)
|
R-Square Value
|
Age of index son (years)
|
0.26
|
0.06
|
1.30 (1.00-1.72)
|
0.13
|
Consumption of local non-chicken meat (y/n)
|
0.56
|
0.04
|
1.75 (1.05-2.92)
|
0.26
|
Consumption of local fish (y/n)
|
0.48
|
0.08
|
1.62 (0.97-2.71)
|
0.23
|
Current residential distance from Khimprom (km)
|
-0.06
|
0.37
|
0.94 (0.82-1.07)
|
0.15
|
Log (PCB 118) (ng/g lipid)
|
0.64
|
<0.001
|
1.90 (1.37-2.63)
|
0.46
|
Weeks of gestation
|
-0.08
|
0.072
|
0.92 (0.84-1.00)
|
0.23
|
Hauser R, Williams P, Peeples L, Altshul L, Korrick S, Revich B, Patterson DG Jr, Turner WE, Lee MM, and Sergeyev O. Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia. Environ Health: A Global Access Science Source. 2005, 4:8 (26 May 2005).
- We submitted an abstract to the 2006 ISEE/ISEA International Conference. It was accepted as a poster presentation.
Local Dietary Contributions to Serum Dioxins, Furans, and Polychlorinated Biphenyls in Peri-Pubertal Russian Boys JS Burns, P Williams, O Sergeyev, E Gitin, T Denisova, S Korrick, MM Lee, B Revich, L Altshul, DG Patterson Jr, WE Turner, AG Ronnenberg, R Hauser. Department of Environmental Health, Harvard School of Public Health. Funded by EPA Grant R82943701 & NIEHS GRANT 5T32-ES007069-25.
Introduction: In Chapaevsk, Russia, where there is high environmental exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs), we assessed the dietary contribution of locally produced foods to serum levels of these compounds in boys.
Methods: Our study sample included 123 boys aged 8-9 years enrolled in 2003. The boys’ initial study visit included physical exams, blood sampling, and completion of semiquantitative food frequency questionnaires by parents or guardians. The blood samples were analyzed for dioxin-like compounds (PCDDs/PCDFs/PCBs) by the Centers for Disease Control and Prevention (CDC). In preliminary analyses, we assessed the associations between categories of local food consumption (fruits and vegetables, meats, poultry, fish, dairy, and eggs) and the log10-transformed sum of PCDDs/PCDFs/coplanar-PCBs using general linear regression models, adjusted for parental education and duration of breast feeding. We then translated estimated changes back to the original scale to calculate percent change in the sum of serum PCDDs/PCDFs/coplanar-PCBs. For food categories with more than one food item, each food item was scored 0 (no local consumption) or 1 (any local consumption) without consideration of quantity consumed. We then computed a percentage of consumed local food (%LF) in each food category for each boy. For example, in the fruit/vegetables category (18 items) if a boy had local consumption of 7 fruit/vegetables items his %LF would be 7/18 (39%).
Results: The median (25th, 75th percentile) concentration for total PCDDs/PCDFs/coplanar-PCBs was 502.8 (430.7, 655.1) pg/g lipids. Fruits and vegetables had the highest %LF (median 39%). Meats had the lowest %LF (median 0%), with only 7 boys eating any local meats. The consumption of local eggs was associated with a 26.1% (95% CI: 6.6%, 49.3%) higher serum total PCDDs/PCDFs/coplanar-PCBs. A 10 unit increase in %LF of fruit/vegetables was associated with a 3.8% (95% CI: 0.9%, 6.8%) increase in serum total PCDDs/PCDFs/coplanar-PCBs. %LF of meat, poultry, fish, or dairy food consumption was not associated with higher serum total PCDDs/PCDFs/coplanar-PCBs.
Discussion and Conclusions: In this cohort of Russian boys, consumption of local eggs and produce were predictors of serum PCDDs/PCDFs/coplanar-PCBs levels. The latter finding was unexpected and may be due to confounding by correlates of produce intake and exposure misclassification since local food consumption was not quantified. Future multivariate analyses are planned to better elucidate the potential independent role of diet as a source of exposure to PCDDs/PCDFs/PCBs, expressed as both serum concentrations and total TEQs.
- Table 3 shows the observed proportion of 8- and 9-year old boys who had reached various criteria for puberty onset: Tanner Stage G2 or greater, Tanner Stage P2 or greater, or testicular volume of greater than 3 ml. In addition, the rightmost column of the table presents the predicted proportion with puberty onset based on fitting an interval censored model to the time to puberty onset using Turnbull's method (1976). The interval censored model is used to estimate the age distribution of puberty onset, taking into account that each boy has either had puberty onset at the time they present for their physical examination, or has not had puberty onset but will at some future time point. The exact age at puberty onset is unknown, but each boy's status and age at the time of their study visit is known. Assuming an underlying normal distribution, the full distribution of the age at puberty onset was estimated using interval censored methods. Figure 1 reveals close agreement with the observed data for ages 8 and 9 (almost all boys had their study visit very close to their birthday) and indicates that the predicted median age of puberty onset is approximately 11.1 years.
Table 3 :Observed and predicted puberty onset by age for 8- to 9- year old boys in Chapaevsk (n=348)
Age (yrs)
|
Tanner Stage
≥ G2
|
Tanner Stage
≥ P2
|
Maximum Testicular
Volume > 3ml
|
Predicted Puberty Onset
Based on Testicular Volume
|
8
|
33 (21%)
|
9 (6%)
|
15 (9%)
|
9%
|
9
|
79 (42%)
|
31 (17%)
|
33 (18%)
|
18%
|
Total
|
112 (32%)
|
40 (12%)
|
48 (14%)
|
|
Missing
|
1
|
1
|
5
|
|
Figure 1: Predicted probability of puberty onset among 348 boys in Chapaevsk (the median age of puberty onset is 11.1 years, illustrated by the horizontal line at 0.5 probability).
* Defined as testicular volume >3 ml of either testes
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. Because the study is a longitudinal study, it will take several years to gather the data necessary to explore the timing and tempo of pubertal development.
Human Subjects:
Approval by Harvard School of Public Health Human Subject Committee and local IRB in Chapaevsk:, Russia December 13 , 2006 – December 12, 2007
Future Activities:
During the coming year, annual follow-up on the boys will continue. We recently 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 : 4 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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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
- 2007 Progress Report
- 2005 Progress Report
- 2004 Progress Report
- 2003 Progress Report
- 2002 Progress Report
- Original Abstract
9 journal articles for this project