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Project Details
Previous pageSeveso Women's Health Study
Project Summary:
Dioxin (TCDD) is the most toxic member of a group of halogenated hydrocarbons that are widespread environmental contaminants. It is produced by various chemical and industrial processes, and is an extremely stable and water insoluble compound, allowing it to persist in the environment and bioaccumulate up the food chain. Dioxin is a known human carcinogen, a potent endocrine disruptor, and may be most harmful to those exposed during infancy and childhood.
On July 10, 1976, a reactor explosion in a chemical plant in Seveso, Italy deposited over 30 kg of dioxin and other chemicals over an 18 km2 area, resulting in the highest residential human exposure to dioxin that has ever been recorded. High animal mortality was observed almost immediately and over 193 cases of chloracne (an acne-like skin condition specific to dioxin exposure) were reported. The surrounding contaminated area was divided into three exposure zones: A, B and R (most heavily contaminated/exposed to least, respectively), based on surface soil dioxin measurements. Shortly after the accident, as part of an ongoing health assessment, serum samples were collected from the residents of these three zones. Much of the serum was used for clinical chemistry tests, and the remaining portion was stored for future studies.
The Seveso Women’s Health Study (SWHS) is a historical cohort study investigating the effects of dioxin exposure on reproductive health of women exposed during the Seveso accident. It was initiated in 1996 and has the benefit of being a large cohort with a wide range of exposures and a biologic measure of serum dioxin levels from blood samples collected soon after the explosion. SWHS is the only comprehensive study to date to investigate the reproductive health of women exposed to dioxin.
Main Findings:
Age and Dioxin Exposure: Women who were youngest at the time of the accident were the most highly exposed to dioxin.
Menarche, Menstruation, Menopause and Dioxin Exposure: Dioxin exposure is associated with a non-significant increased risk of starting menstruation earlier among women who were less than 5 years old at exposure. Women exposed premenarcheally have an approximate one day increase in menstrual cycle length for every 10-fold increase in dioxin levels. There is a non-monotonic dose-response relationship between dioxin exposure and earlier onset of natural menopause for dioxin levels up to 100 ppt, but not above.
Fertility, Birth Outcomes and Dioxin Exposure: Dioxin exposure is significantly associated with increased risk for infertility and longer time to pregnancy. There is some evidence that dioxin exposure is also associated with lower birth weight (especially among pregnancies that occurred within one dioxin half-life of the explosion), and reduced duration of lactation.
Women’s Health and Dioxin Exposure: Among women highly exposed to dioxin, there is a decreased risk of uterine fibroids, and a non-significant increased risk of endometriosis. Lastly, after 32 years of follow-up, dioxin exposure was associated significantly with an increased risk of all cancer, and non-significantly with an increased risk of breast cancer.
Policy, Practice or Research Impacts:
SWHS is the only comprehensive study to date to investigate the reproductive health of women exposed to dioxin.
Project Type:
Topics:
Populations:
Contact Person:
Marcy Warner
Contact Person's Email Address:
mwarner@berkeley.edu
Department/Center:
Center for Environmental Research and Children's Health
Principal Investigators:
Brenda Eskenazi
Research Publications and Reports:
Warner M, Eskenazi B, Mocarelli P, Samuels S, Needham L, Patterson D, Brambilla P. Serum dioxin concentrations and breast cancer risk in the Seveso women’s health study. Environ Health Perspect, 110(7): 625-8, 2002.
Eskenazi B, Mocarelli P, Warner M, Samuels S, Vercellini P, Olive D, Needham LL, Patterson DG Jr, Brambilla P, Gavoni N, Casalini S, Panazza S, Turner W, Gerthoux PM. Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy. Environ Health Perspect, 110(7):629-34, 2002.
Eskenazi B, Warner M, Mocarelli P, Samuels S, Needham LL, Patterson DG Jr, Lippman S, Vercellini P, Gerthoux PM, Brambilla P, Olive D. Serum dioxin concentrations and menstrual cycle characteristics. Am J Epidemiol, 156(4): 383-92, 2002.
Eskenazi B, Mocarelli P, Warner M, Chee WY, Gerthoux PM, Samuels S, Needham LL, Patterson DG Jr. Maternal serum dioxin levels and birth outcomes in women of Seveso, Italy. Environ Health Perspect, 111(7): 947-53, 2003.
Eskenazi B, Mocarelli P, Warner M, Needham LL, Patterson DG Jr, Samuels S, Turner W, Gerthoux PM, Brambilla P. Relationship of serum TCDD concentrations and age at exposure of female residents of Seveso, Italy. Environ Health Perspect, 112(1): 22-7, 2004.
Warner M, Samuels S, Mocarelli P, Gerthoux, PM, Needham LL, Patterson DG Jr, Eskenazi B. Serum dioxin concentrations and age at menarche. Environ Health Perspect, 112(13): 1289-92, 2004.
Warner M, Eskenazi B, Patterson DG, Clark G, Turner WE, Bonsignore L, Mocarelli P, Gerthoux PM. Dioxin-like TEQ of women from the Seveso, Italy area by ID-HRGC/HRMS and CALUX. Jour Exp Anal Environ Epidem, 15(4): 310-8, 2005.
Eskenazi B, Warner M, Marks AR, Samuels S, Gerthoux PM, Vercellini P, Olive DL, Needham L, Patterson D Jr, Mocarelli P. Serum dioxin concentrations and age at menopause. Environ Health Perspect, 113(7): 858-62, 2005.
Warner M, Eskenazi B, Olive DL, Samuels S, Quick-Miles S, Vercellini P, Gerthoux PM, Needham L, Patterson DG, Mocarelli P. Serum dioxin concentrations and quality of ovarian function in women of Seveso. Environ Health Perspect, 115(3): 336-40, 2007.
Eskenazi B, Warner M, Samuels S, Young J, Gerthoux PM, Needham L, Patterson D, Olive D, Gavoni N, Vercellini P, Mocarelli P. Serum dioxin concentrations and risk of uterine leiomyoma in the Seveso Women’s Health Study. Am J Epidem, 166(1): 79-87, 2007.
Eskenazi B, Warner M, Marks AR, Samuels S, Needham L, Brambilla P, Mocarelli P. Serum dioxin concentrations and time to pregnancy. Epidemiology, 21(2): 224-31, 2010.
Warner M, Mocarelli P, Samuels S, Needham LL, Brambilla P, Eskenazi B. Dioxin exposure and cancer risk in the Seveso Women’s Health Study. Environ Health Perspect, 119(12): 1700-5, 2011.
Website for Project or Program:
Funder/Client:
National Institute for Environmental Health Science (NIEHS); National Institutes of Health (NIH); Endometriosis Association; US Environmental Protection Agency (EPA); Regione Lombardia and Fondazione Lombardia Ambiente, Milan, Italy
Location - States:
USA
Location - Countries:
Italy