Predicting health effects of exposures to compounds with estrogenic activity: methodological issues.

Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment approach, some researchers have concluded that exposure to environmental estrogens is not associated with estrogen receptor (ER)-mediated health effects. Their rationale cites the low potency of these compounds in in vitro assays relative to estradiol, and the widespread exposure to pharmaceutical, endogenous, and dietary estrogens. This reasoning relies on two assumptions: that the relative estrogenic potency in in vitro assays is predictive of the relative potency for the most sensitive in vivo estrogenic effect; and that all estrogens act via the same mechanism to produce the most sensitive in vivo estrogenic effect. Experimental data reviewed here suggest that these assumptions may be inappropriate because diversity in both mechanism and effect exists for estrogenic compounds. Examples include variations in ER-ligand binding to estrogen response elements, time course of nuclear ER accumulation, patterns of gene activation, and other mechanistic characteristics that are not reflected in many in vitro assays, but may have significance for ER-mediated in vivo effects. In light of these data, this report identifies emerging methodological issues in risk assessment for estrogenic compounds: the need to address differences in in vivo end points of concern and the associated mechanisms; pharmacokinetics; the crucial role of timing and duration of exposure; interactions; and non-ER-mediated activities of estrogenic compounds

Self-Reported Chemicals Exposure, Beliefs About Disease Causation, and Risk of Breast Cancer in the Cape Cod Breast Cancer and Environment Study: A Case-Control Study

BACKGROUND: Household cleaning and pesticide products may contribute to breast cancer because many contain endocrine disrupting chemicals or mammary gland carcinogens. This population-based case-control study investigated whether use of household cleaners and pesticides increases breast cancer risk. METHODS: Participants were 787 Cape Cod, Massachusetts, women diagnosed with breast cancer between 1988 and 1995 and 721 controls. Telephone interviews asked about product use, beliefs about breast cancer etiology, and established and suspected breast cancer risk factors. To evaluate potential recall bias, we stratified product-use odds ratios by beliefs about whether chemicals and pollutants contribute to breast cancer; we compared these results with odds ratios for family history (which are less subject to recall bias) stratified by beliefs about heredity. RESULTS: Breast cancer risk increased two-fold in the highest compared with lowest quartile of self-reported combined cleaning product use (Adjusted OR = 2.1, 95% CI: 1.4, 3.3) and combined air freshener use (Adjusted OR = 1.9, 95% CI: 1.2, 3.0). Little association was observed with pesticide use. In stratified analyses, cleaning products odds ratios were more elevated among participants who believed pollutants contribute "a lot" to breast cancer and moved towards the null among the other participants. In comparison, the odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot" (OR = 2.6, 95% CI: 1.9, 3.6) and not elevated among others (OR = 0.7, 95% CI: 0.5, 1.1). CONCLUSIONS: Results of this study suggest that cleaning product use contributes to increased breast cancer risk. However, results also highlight the difficulty of distinguishing in retrospective self-report studies between valid associations and the influence of recall bias. Recall bias may influence higher odds ratios for product use among participants who believed that chemicals and pollutants contribute to breast cancer. Alternatively, the influence of experience on beliefs is another explanation, illustrated by the protective odds ratio for family history among women who do not believe heredity contributes "a lot." Because exposure to chemicals from household cleaning products is a biologically plausible cause of breast cancer and avoidable, associations reported here should be further examined prospectively.Massachusetts Legislature; Massachusetts Department of Public Health; Susan S. Bailis Breast Cancer Research Fund at Silent Spring Institute; United States Centers for Disease Control and Prevention (R01 DP000218-01, 1H75EH000377-01

The South Dakota Grain Marketing System

This paper deals with the production and sale of grain, and analyzes the economic structure and cost relationships of South Dakota’s grain marketing system

Wheat Transportation in Perspective

This publication discusses the history of the various types of transportation used to get wheat to market. The historic importance of railways in wheat transportation and railroad regulation, as well as the role of trucks and barges, is also explained

Cell

AbstractPorB of the pathogenic Neisseria species belongs to the large family of pore-forming proteins (porins) produced by gram-negative bacteria. PorB is exceptional in that it is capable of translocating vectorially into membranes of infected target cells and functions in the infection process. Here we report on an unexpected similarity between Neisserial PorB and mitochondrial porins. Both porin classes interact with purine nucleoside triphosphates, which down-regulate pore size and cause a shift in voltage dependence and ion selectivity. Patch-clamp analyses indicate that PorB channel activity is tightly regulated in intact epithelial cells. In light of recent findings on the pivotal role of PorB in virulence and the prevention of phagosome lysosome fusion, these data provide important mechanistic clues on the intracellular pathogen accommodation reminiscent of mitochondrial endosymbiosis

Arriving at Wheat Marketing Decisions

This focus of this bulletin is on various facets of wheat marketing, including historic market information, current market information, and a basic wheat marketing information

Exposure to Perfluoroalkyl Substances in a Cohort of Women Firefighters and Office Workers in San Francisco.

Studies of firefighters have shown increased exposures to carcinogenic compounds and elevated rates of certain cancers compared to the general population, yet this research has focused almost exclusively on men. To address this gap, the Women Firefighters Biomonitoring Collaborative created a biological sample archive and analyzed levels of perfluoroalkyl substances (PFAS) among women firefighters (N = 86) and office workers (N = 84) in San Francisco. Serum samples were collected and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure and compare PFAS levels between firefighters and office workers. 7 of 12 PFAS congeners were detected in the least 70% of the study population, and 4 congeners were detected in 100% of participants. In regression models comparing PFAS levels by occupation and adjusting for potential confounders, firefighters had higher geometric mean concentrations of PFAS compared to office workers PFHxS (2.22 (95% CI = 1.55, 3.18)), PFUnDA (1.83 (95% CI = 0.97, 3.45)), and PFNA (1.26 (95% CI = 1.01, 1.58)). Among firefighters, occupational position predicted exposure-firefighters and officers had higher PFNA, PFOA, PFDA, and PFUnDA levels compared to drivers. Women firefighters are exposed to higher levels of some PFAS compared to office workers, suggesting that some of these exposures may be occupationally related

The precautionary principle in environmental science.

Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy

Integrating Exposure Knowledge and Serum Suspect Screening as a New Approach to Biomonitoring: An Application in Firefighters and Office Workers.

Firefighters (FF) are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns in women FFs, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so, it may not detect relevant, lesser known, exposures. The Women FFs Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap. Using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, we sought to identify candidate chemicals of interest in serum samples from 83 women FFs and 79 women office workers (OW) in San Francisco. We identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 722 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected tentatively identified chemicals for confirmation based on the following criteria: (1) detection frequency or peak area differences between OW and FF; (2) evidence of mammary carcinogenicity, estrogenicity, or genotoxicity; and (3) not currently measured in large biomonitoring studies. We detected 620 chemicals that matched 300 molecular formulas in the WFBC database, including phthalate metabolites, phosphate flame-retardant metabolites, phenols, pesticides, nitro and nitroso compounds, and per- and polyfluoroalkyl substances. Of the 20 suspect chemicals selected for validation, 8 were confirmed-including two alkylphenols, ethyl paraben, BPF, PFOSAA, benzophenone-3, benzyl p-hydroxybenzoate, and triphenyl phosphate-by running a matrix spike of the reference standards and using m/z, retention time, and the confirmation of at least two fragment ions as criteria for matching. GSS provides a powerful high-throughput approach to identify and prioritize novel chemicals for biomonitoring and health studies