Grantee Research Project Results
Final Report: Reproductive Health and Dioxin Exposure of Females of Seveso
EPA Grant Number: R824761Title: Reproductive Health and Dioxin Exposure of Females of Seveso
Investigators: Eskenazi, Brenda
Institution: University of California - Berkeley
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1995 through September 1, 1998
Project Amount: $426,554
RFA: Human Health Risk Assessment (1995) RFA Text | Recipients Lists
Research Category: Environmental Justice , Human Health
Objective:
Funding for this study was obtained primarily from the National Institute of Environmental Health Sciences (NIEHS) and the Environmental Protection Agency (EPA). The specific aims of this study were to:
1. Compare the rates of endometriosis in females who were 0 to 30 years old in 1976, who in 1976 resided in Zones A, Bmax, or Bmin, and who had at least one serum specimen collected between 1976 and 1980.
2. Compare the serum TCDD levels among women with endometriosis to those among women without endometriosis in a cohort study design.
3. Determine whether the rates of other adverse reproductive endpoints are dose-dependent. With additional funding from NIEHS Center at UCB, we were able to expand the cohort to interview women who were 31 to 40 years old in 1976. With new funding from the NIH, we will determine whether the rates of other adverse reproductive endpoints including age of menarche, menstrual cycle characteristics, clinical infertility, age of menopause, breast cancer, and birth outcomes of pregnancies conceived after the explosion are related to serum TCDD level.
4. Validate the criteria for assigning probability of endometriosis used for the Seveso Women's Health Study (SWHS) in a hospital-base population undergoing laparoscopy.
Summary/Accomplishments (Outputs/Outcomes):
The following was accomplished in Year 4:
- Of the 1,273 women who were eligible for the SWHS (0-40 years in 1976), a total of 981 (80 percent) agreed to participate. To date, all 981 women (100 percent) have had their serum TCDD analyzed.
- In January 2000, a dataset was prepared from the SWHS data for graduate student, Sherri Lippman, to use for her M.P.H. thesis titled, "The association of uterine fibroids and pelvic pain in a population-based cohort". Ms. Lippman is currently writing it up to submit for publication by the end of 2000.
- In February 2000, data analysis of TCDD exposure data for the full cohort was completed. A summary of serum TCDD levels by select characteristics of study participants is presented in Table 1. We expect to finalize a manuscript summarizing these data in January 2001.
- In March 2000, Paolo Mocarelli traveled to Berkeley to meet with Drs. Eskenazi, Warner, and Samuels. The purpose of his visit was to review a preliminary draft of the endometriosis manuscript. During his visit, a conference call was held with collaborators from CDC and Italy to get their input as well.
- In March 2000, data analysis was initiated to examine the association of TCDD and breast cancer in the SWHS cohort. Originally, this was to be a small sub-analysis conducted by Dr. Warner for presentation purposes at a Scientific Meeting. Despite the small sample size, the findings are rather interesting, thus we withdrew the presentation. We plan to submit a manuscript for publication in January 2001.
- In April 2000, an application was submitted to copyright the Seveso Women's Health Study questionnaire and examination study instruments.
- In April 2000, data sets were prepared to initiate data analysis of specific aims: (1) menstrual cycle characteristics, and (2) birthweight of pregnancies conceived after the explosion in 1976. We expect to complete these analyses and initiate manuscript writing in early 2001.
- In June 2000, the manuscript titled, "Seveso Women's Health Study: Does zone of residence predict individual TCDD exposure", which summarizes the data presented by Dr. Eskenazi at the Dioxin 99 Conference in Venice was accepted for publication in Chemosphere.
- In July 2000, Paolo Mocarelli traveled to Berkeley to meet with Drs. Eskenazi, Warner, and Samuels. The purpose of his visit was to finalize the endometriosis manuscript and discuss possible future grant proposals related to this cohort. During his visit, a conference call was held with collaborators from CDC and Italy to get their input as well.
- In August 2000, Drs. Eskenazi and Warner together attended the Dioxin 2000 Conference in Monterey, California. Drs. Eskenazi and Needham co-chaired the session titled, "Epidemiology-What Have We Learned". While there, Drs. Eskenazi and Warner also met with Drs. Mocarelli, Needham, Patterson and Mr. Turner to make final revisions on the endometriosis manuscript.
- In August 2000, Dr. Eskenazi traveled to Singapore for the International Congress of Occupational Health, where she made an oral presentation titled "Potential associations of TCDD exposure and adverse reproductive outcomes in humans".
- In September 2000, the endometriosis manuscript was submitted for publication and is currently under JAMA peer-review.
- Data collection (begun in May 1998) for the Endometriosis Validation Study, including drawing a blood sample from each woman, was completed in February 2000. Blood samples were sent to CDC and are currently undergoing analysis for the full spectrum of dioxins and furans, PCBs, and organochlorines.
- In May 2000, a poster presentation of preliminary findings from the Endometriosis Validation Study, "Validation Study of non-surgical diagnosis of endometriosis" was made at the Endometriosis 2000 World Congress in London.
- A total of 110 women were recruited and 90 participated. The data analysis for the interview and exam phase of the study, which required the use of CART, Classification and Regression Tree Analysis, was completed in October 2000. We recently submitted a manuscript of the results of this study for publication. In 2001, once the CDC analyses are complete, we will examine the relation of these chemicals with endometriosis as a case-control study.
Conclusions:
There is extensive animal evidence suggesting effects of TCDD exposure on female reproductive endpoints, yet there is a lack of confirmation of these findings in large well-designed studies in humans. The ability to quantify individual level TCDD exposure from sera collected in 1976 for the Seveso cohort affords a unique opportunity to evaluate the potential dose-response relationship between TCDD exposure and a spectrum of reproductive endpoints in humans. To date, we have completed the endometriosis analysis. We found a doubled, non-significant, risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose-response relation. There are a number of reproductive outcomes in the Seveso cohort for which data analysis is almost complete including breast cancer, menstrual cycle characteristics, birthweight of pregnancies conceived after 1976, and age of menarche. We expect next year to be highly productive, with great potential to provide results derived from a large, well-designed study in humans that can either confirm or refute the previously reported animal findings.Journal Articles on this Report : 2 Displayed | Download in RIS Format
Other project views: | All 4 publications | 2 publications in selected types | All 2 journal articles |
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Type | Citation | ||
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Eskenazi B, Mocarelli P, Warner M, Samuels S, Vercellini P, Olive D, Needham L, Patterson D, Brambilla P. Seveso Women's Health Study: a study of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive health. Chemosphere, Volume 40, Issues 9-11, May-June 2000, Pages 1247-1253. |
R824761 (Final) |
not available |
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Eskenazi B, Mocarelli P, Warner M, Samuels S, Needham L, Patterson D, Brambilla P, Gerthoux P, Turner W, Casalini S, Cazzaniga M. Seveso women's health study: does zone of residence predict individual TCDD exposure? Chemosphere, Volume 43, Issues 4-7, May 2001, Pages 937-942. |
R824761 (Final) |
not available |
Supplemental Keywords:
dioxin, furan, PCBs, TCDD, human health, reproductive health., RFA, Health, Scientific Discipline, Geographic Area, Environmental Chemistry, Health Risk Assessment, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Risk Assessments, Children's Health, Biology, Endocrine Disruptors - Human Health, International, Seveso, females, TCDD, endocrine disrupting chemicals, environmental mutagens, human exposure, population-based human data, toxic environmental contaminants, reproductive health, interviews, dioxin exposureProgress 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.