Serum levels and other health impacts

PANNA Summary: Consumers of Great Lakes sports fish have had increased levels of DDE in their bodies, and higher chances of developing diabetes than others, according to research published in the July 2009 issue of Environmental Health Perspectives. The study included 471 adults; those with higher levels of DDE in their blood were more likely to develop diabetes. Fortunately, with the banning of DDT by the U.S. and many other countries in the 1970s, and its listing with eleven other pesticides and persistent organic pollutants (POPs) by more than 155 nations for global phaseout under the Stockholm Convention since 2004, levels of DDE in people who consume Great Lakes sports fish have begun to decline significantly.

Abstract: Background: Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs) . Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking.

Objectives: This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers.

Methods: The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status.

Results: DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status.

Conclusions: This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.

Maternal levels of dichlorodiphenyl-dichloroethylene (DDE) may increase weight and body mass index in adult female offspring. Occupational and Environmental Medicine December 2008

Panna Summary: Researchers at Michigan State University have discovered that prenatal exposure to a break-down product of DDT -- an insecticide commonly used in the U.S. until it was banned in 1973 -- may play a role in the obesity epidemic in women. The researchers found that women with intermediate levels of DDE in their bodies gained an average of 13 pounds of excess weight. Women with higher levels of DDE gained more than 20 excess pounds.

Abstract: Objectives: To investigate the effect of prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyl-dichloroethylene (DDE) on weight, height and body mass index (BMI) in adult female offspring of the Michigan fisheater cohort examined between 1973 and 1991.

Methods: 259 mothers from the Michigan fisheater cohort were studied. Prenatal exposure to PCBs and DDE was estimated by extrapolating maternal measurements to the time that the women gave birth. 213 daughters aged 20–50 years in 2000 were identified and 83% of them participated in at least one of two repeated investigations in 2001/02 (n = 151) and 2006/07 (n = 129). To assess the effect of prenatal PCB and DDE exposure on anthropometric measurements, generalised estimating equations nested for repeated measurements (2001/02 and 2006/07) and for sharing the same mother were used. We controlled for maternal height and BMI and for daughters’ age, birth weight, having been breastfed and number of pregnancies.

Results: Maternal height and BMI were significant predictors of the daughters’ height, weight and BMI. Low birth weight (<2500 g) was significantly associated with reduced adult offspring weight and BMI. The weight and BMI of adult offspring were statistically significantly associated with the extrapolated prenatal DDE levels of their mothers. Controlling for confounders and compared to maternal DDE levels of <1.503 µg/l, offspring BMI was increased by 1.65 when prenatal DDE levels were 1.503–2.9 µg/l and by 2.88 if levels were >2.9 µg/l. Prenatal PCB levels showed no effect.

Conclusion:Prenatal exposure to the oestrogenic endocrine-disrupting chemical DDE may contribute to the obesity epidemic in women.

DDT and Breast Cancer in Young Women: New Data on the Significance of Age at Exposure. Environmental Health Perspectives August 2007

PANNA Summary:

Abstract:Previous studies of DDT and breast cancer assessed exposure later in life when the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned.

Objectives: We investigated whether DDT exposure in young women during the period of peak DDT use predicts breast cancer.

Methods: We conducted a prospective, nested case–control study with a median time to diagnosis of 17 years using blood samples obtained from young women during 1959–1967. Subjects were members of the Child Health and Development Studies, Oakland, California, who provided blood samples 1–3 days after giving birth (mean age, 26 years) . Cases (n = 129) developed breast cancer before the age of 50 years. Controls (n = 129) were matched to cases on birth year. Serum was assayed for p,p´-DDT, the active ingredient of DDT ; o,p´-DDT, a low concentration contaminant ; and p,p´-DDE, the most abundant p,p´-DDT metabolite.

Results: High levels of serum p,p´-DDT predicted a statistically significant 5-fold increased risk of breast cancer among women who were born after 1931. These women were under 14 years of age in 1945, when DDT came into widespread use, and mostly under 20 years as DDT use peaked. Women who were not exposed to p,p´-DDT before 14 years of age showed no association between p,p´-DDT and breast cancer (p = 0.02 for difference by age) .

Conclusions: Exposure to p,p´-DDT early in life may increase breast cancer risk. Many U.S. women heavily exposed to DDT in childhood have not yet reached 50 years of age. The public health significance of DDT exposure in early life may be large.

McGlynn, KA, Quraishi, SM, Graubard, BI, Weber, JP, Rubertone MV, Erickson, RL. Persistent Organochlorine Pesticides and Risk of Testicular Germ Cell Tumors. Journal of the National Cancer institute May 2008 100: 603.

PANNA Summary: Exposure to DDT and other organochlorine pesticides has been suggested to cause a risk of testicular germ cell tumors. The authors tested serum and found that an increased exposure to DDE, a breakdown of DDT, may be associated with the risk of developing testicular germ cell tumors, especially during fetal life or from breastmilk.

Abstract: Background: Exposure to endocrine-disrupting chemicals, such as persistent organochlorine pesticides, has been suggested to increase the risk of testicular germ cell tumors (TGCTs).

Methods: To study the relationship of POP exposure to TGCT risk, prediagnostic serum samples from 754 case subjects and 928 control subjects enrolled in the Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study were analyzed for cis-nonachlor, trans-nonachlor, oxychlordane, total chlordanes, β-hexachlorocyclohexane, mirex, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyltrichloroethane. Adjusted odds ratios (ORs) and their associated 95% confidence intervals (CIs) for the risk of TGCT overall and for the histological subgroups, seminoma and nonseminoma, were estimated using multivariable logistic regression. All statistical tests were two-sided.

Results: TGCT risk was statistically significantly associated with higher plasma levels of p,p'-DDE (for highest quartile [Q4] vs lowest quartile [Q1], OR = 1.71, 95% CI = 1.23 to 2.38, Ptrend = .0002) and of two chlordane components, cis-nonachlor (Q4 vs Q1, OR = 1.56, 95% CI = 1.11 to 2.18, Ptrend = .009) and trans-nonachlor (Q4 vs Q1, OR = 1.46, 95% CI = 1.07 to 2.00, Ptrend = .026). Seminoma risk was statistically significantly associated with p,p'-DDE (Q4 vs Q1, OR = 1.91, 95% CI = 1.22 to 2.99, Ptrend = .0008), cis-nonachlor (Q4 vs Q1, OR = 1.93, 95% CI = 1.27 to 2.93, Ptrend = .0045), trans-nonachlor (Q4 vs Q1, OR = 1.72, 95% CI = 1.11 to 2.67, Ptrend = .033), and a chlordane metabolite, oxychlordane (Q4 vs Q1, OR = 1.64, 95% CI = 1.04 to 2.60, Ptrend = .048), whereas nonseminoma risk showed a statistically significant association with p,p'-DDE only (Q4 vs Q1, OR = 1.63, 95% CI = 1.10 to 2.42, Ptrend = .0044).

Conclusions: Increased exposure to p,p'-DDE may be associated with the risk of both seminomatous and nonseminomatous TGCTs, whereas exposure to chlordane compounds and metabolites may be associated with the risk of seminoma. Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these persistent organic pesticides during fetal life or via breast feeding may increase the risk of TGCT in young men.

Julia Green Brody, PhD , Kirsten B. Moysich, PhD, Olivier Humblet,MS, Kathleen R. Attfield, BS, Gregory P. Beehler, MA, Ruthann A. Rudel,MS Environmental pollutants and breast cancer. Cancer 2007 109(S12):2667-2711

PANNA Summary: After analyzing the research already done onenvironmental pollutants and breast cancer, the authors conclude that more research measuring toxicity needs to be done. They also suggest the development of better methods to measure exposure to toxic pollutants. Progress has been made in the last five years.

Abstract: Laboratory research has shown that numerous environmental pollutants cause mammary gland tumors in animals; are hormonally active, specifically mimicking estrogen, which is a breast cancer risk factor; or affect susceptibility of the mammary gland to carcinogenesis. An assessment of epidemiologic research on these pollutants identified in toxicologic studies can guide future research and exposure reduction aimed at prevention. The PubMed database was searched for relevant literature and systematic critical reviews were entered in a database available at URL:www.silentspring.org/sciencereview and URL: www.komen.org/environment(accessed April 10, 2007). Based on a relatively small number of studies, the evidence to date generally supports an association between breast cancer and polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in conjunction with certain genetic polymorphisms involved in carcinogen activation and steroid hormone metabolism. Evidence regarding dioxins and organic solvents is sparse and methodologically limited but suggestive of an association. Methodologic problems include inadequate exposure assessment, a lack ofaccess to highly exposed and unexposed populations, and a lack of preclinical markers to identify associations that may be obscured by disease latency. Among chemicals identified in toxicologic research as relevant to breast cancer, many have not been investigated in humans.The development of better exposure assessment methods is needed to fillthis gap. In the interim, weaknesses in the epidemiologic literature argue for greater reliance on toxicologic studies to develop national policies to reduce chemical exposures that may be associated with breast cancer. Substantial research progress in the last 5 years suggests that the investigation of environmental pollutants will lead to strategies to reduce breast cancer risk. Cancer 2007. © 2007American Cancer Society. 1Silent Spring Institute, Newton,Massachusetts 2 Department of Epidemiology, Roswell Park CancerInstitute, Buffalo, New York email: Julia Green Brodybrody@silentspring.org Correspondence to Julia Green Brody, SilentSpring Institute, 29 Crafts Street, Newton, MA 02458 Fax: (617) 332-4284

Cohn, BA, MS Wolff, PM Cirillo and RI Sholtz. DDT and breast cancerin young women: New data on the significance of age at exposure. Environmental Health Perspectives 2007 115(10): 1406-1414.

PANNA Summary: The authors compared DDT in blood from women in Oakland,California taken between 1959-1967 and breast cancer in the same women years later. Women with high percentages of DDT in their blood were five times more likely to have breast cancer.

Abstract: Background: Prior studies of DDT and breast cancer assessed exposure later in lifewhen the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned.

Objectives: Investigate whether DDT exposure in young women during peak DDT use predicts breast cancer.

Methods: We conducted a prospective, nested case-control study with a mediantime to diagnosis of 17 years using blood samples obtained from young women from 1959-1967. Subjects were members of the Child Health and Development Studies, Oakland, California, who provided blood samples 1to 3 days after giving birth (mean age 26 years). Cases (n=129)developed breast cancer before age 50 years. Controls (n=129) were matched to cases on birth year. Serum was assayed for p,p’-DDT, the active ingredient of DDT, o,p’-DDT a low concentration contaminant, andp,p’-DDE, the most abundant p,p’-DDT metabolite.

Results: High levels of serum p,p’-DDT predicted a statistically significantfive-fold increased risk of breast cancer among women who were born after 1931. These women were under age 14 in 1945, when DDT came into widespread use and mostly under age 20 as DDT use peaked. Women who were not exposed to p,p’-DDT before age 14 showed no association between p,p’-DDT and breast cancer (p=0.02 for difference by age).

Conclusions: Exposure to p,p’-DDT early in life may increase breast cancer risk. Many U.S. women heavily exposed to DDT in childhood have not yet reached age 50. The public health significance of DDT exposure in earlylife may be large.

Full text: http://www.ehponline.org/docs/2007/10260/abstract.html