The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

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EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers.

Health effects of chronic pesticide exposure: cancer and neurotoxicity.

https://www.itqb.unl.pt/~imartins/Czaplicka_2004.pdf

Sources and transformations of chlorophenols in the natural environment.

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: wwwsilentspringorg/sciencereview and URL: wwwkomenorg/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 of access 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 fill this 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

/pdf/environmental-pollutants-and-breast-cancer-epidemiologic-2rx280n6y1.pdf

Environmental pollutants and breast cancer: epidemiologic studies.

This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal...

Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants

The authors examined cancer mortality in a historical cohort study of 21,863 male and female workers in 36 cohorts exposed to phenoxy herbicides, chlorophenols, and dioxins in 12 countries. Subjects in this updated and expanded multinational study coordinated by the International Agency for Research on Cancer were followed from 1939 to 1992. Exposure was reconstructed using job records, company exposure questionnaires, and serum and adipose tissue dioxin levels. Among workers exposed to phenoxy herbicides contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or higher chlorinated dioxins, mortality from soft-tissue sarcoma (6 deaths; standardized mortality ratio (SMR) = 2.03, 95% confidence interval (CI) 0.75-4.43) was higher than expected from national mortality rates. Mortality from all malignant neoplasms (710 deaths; SMR = 1.12, 95% CI 1.04-1.21), non-Hodgkin's lymphoma (24 deaths; SMR = 1.39, 95% CI 0.89-2.06), and lung cancer (225 deaths; SMR = 1.12, 95% CI 0.98-1.28) was slightly elevated. Risks for all neoplasms, for sarcomas, and for lymphomas increased with time since first exposure. In workers exposed to phenoxy herbicides with minimal or no contamination by TCDD and higher chlorinated dioxins, mortality from all neoplasms (398 deaths; SMR = 0.96, 95% CI 0.87-1.06), non-Hodgkin's lymphoma (9 deaths; SMR = 1.00), and lung cancer (148 deaths; SMR = 1.03) was similar to that expected, and mortality from soft-tissue sarcoma was slightly elevated (2 deaths; SMR = 1.35). In a Poisson regression analysis, workers exposed to TCDD or higher chlorinated dioxins had an increased risk for all neoplasms (rate ratio = 1.29, 95% CI 0.94-1.76) compared with workers from the same cohort exposed to phenoxy herbicides and chlorophenols but with minimal or no exposure to TCDD and higher chlorinated dioxins. These findings indicate that exposure to herbicides contaminated with TCDD and higher chlorinated dioxins may be associated with a small increase in overall cancer risk and in risk for specific cancers.

David Coggon

Papers

Cancer Mortality in Workers Exposed to Phenoxy Herbicides, Chlorophenols, and Dioxins An Expanded and Updated International Cohort Study