Developmental Exposure of Rats to Chlorpyrifos Elicits Sex-Selective Hyperlipidemia and Hyperinsulinemia in Adulthood

Developmental exposure to chlorpyrifos alters cell signaling both in the brain and in peripheral tissues, affecting the responses to a variety of neurotransmitters and hormones. We administered 1 mg/kg/day chlorpyrifos to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, chlorpyrifos-exposed animals displayed elevations in plasma cholesterol and triglycerides, without underlying alterations in nonesterified free fatty acids and glycerol. This effect was restricted to males. Similarly, in the postprandial state, male rats showed hyperinsulinemia in the face of normal circulating glucose levels but demonstrated appropriate reduction of circulating insulin concentrations after fasting. These outcomes and sex selectivity resemble earlier findings at the cellular level, which identified hepatic hyperresponsiveness to gluconeogenic inputs from β-adrenoceptors or glucagon receptors. Our results thus indicate that apparently subtoxic neonatal chlorpyrifos exposure, devoid of effects on viability or growth but within the parameters of human fetal or neonatal exposures, produce a metabolic pattern for plasma lipids and insulin that resembles the major adult risk factors for atherosclerosis and type 2 diabetes mellitus

A High-Level Disinfection Standard for Land-Applied Sewage Sludges (Biosolids)

associated with land-applied sewage sludges primarily involve irritation of the skin, mucous membranes, and the respiratory tract accompanied by opportunistic infections. Volatile emissions and organic dusts appear to be the main source of irritation. Occasionally, chronic gastrointestinal problems are reported by affected residents who have private wells. To prevent acute health effects, we recommend that the current system of classifying sludges based on indicator pathogen levels (Class A and Class B) be replaced with a single high-level disinfection standard and that methods used to treat sludges be improved to reduce levels of irritant chemicals, especially endotoxins. A national opinion survey of individuals impacted by or concerned about the safety of land-application practices indicated that most did not consider the practice inherently unsafe but that they lacked confidence in research supported by federal and state agencie

Global Farm Animal Production and Global Warming: Impacting and Mitigating Climate Change

BACKGROUND: The farm animal sector is the single largest anthropogenic user of land, contributing to many environmental problems, including global warming and climate change. OBJECTIVES: The aim of this study was to synthesize and expand upon existing data on the contribution of farm animal production to climate change. METHODS: We analyzed the scientific literature on farm animal production and documented greenhouse gas (GHG) emissions, as well as various mitigation strategies. DISCUSSIONS: An analysis of meat, egg, and milk production encompasses not only the direct rearing and slaughtering of animals, but also grain and fertilizer production for animal feed, waste storage and disposal, water use, and energy expenditures on farms and in transporting feed and finished animal products, among other key impacts of the production process as a whole. CONCLUSIONS: Immediate and far-reaching changes in current animal agriculture practices and consumption patterns are both critical and timely if GHGs from the farm animal sector are to be mitigated

State-of-the-Science Workshop Report: Issues and Approaches in Low-Dose–Response Extrapolation for Environmental Health Risk Assessment

Low-dose extrapolation model selection for evaluating the health effects of environmental pollutants is a key component of the risk assessment process. At a workshop held in Baltimore, Maryland, on 23–24 April 2007, sponsored by U.S. Environmental Protection Agency and Johns Hopkins Risk Sciences and Public Policy Institute, a multidisciplinary group of experts reviewed the state of the science regarding low-dose extrapolation modeling and its application in environmental health risk assessments. Participants identified discussion topics based on a literature review, which included examples for which human responses to ambient exposures have been extensively characterized for cancer and/or noncancer outcomes. Topics included the need for formalized approaches and criteria to assess the evidence for mode of action (MOA), the use of human versus animal data, the use of MOA information in biologically based models, and the implications of interindividual variability, background disease processes, and background exposures in threshold versus nonthreshold model choice. Participants recommended approaches that differ from current practice for extrapolating high-dose animal data to low-dose human exposures, including categorical approaches for integrating information on MOA, statistical approaches such as model averaging, and inference-based models that explicitly consider uncertainty and interindividual variability

Long-Term Traffic-Related Exposures and Asthma Onset in Schoolchildren in Oslo, Norway

BACKGROUND: Whether there is a causal relation between long-term exposure to traffic and asthma development is so far not clear. This may be explained by inaccurate exposure assessment. OBJECTIVE: We investigated the associations of long-term traffic-related exposures with asthma onset assessed retrospectively and respiratory symptoms in 9- to 10-year-old children. METHODS: We collected information on respiratory outcomes and potential confounding variables by parental questionnaire in 2,871 children in Oslo. Nitrogen dioxide exposure was assessed by the EPISODE dispersion model and assigned at updated individual addresses during lifetime. Distance to major road was assigned at birth address and address by date of questionnaire. Cox proportional hazard regression and logistic regression were used. RESULTS: We did not find positive associations between any long-term traffic-related exposure and onset of doctor-diagnosed asthma. An interquartile range (IQR) increase of NO(2) exposure before asthma onset was associated with an adjusted risk ratio of 0.82 [95% confidence interval (CI), 0.67-1.02]. Handling early asthma cases (children /= 4 years of age) were positive but not statistically significant. For current symptoms, an IQR increase of previous year's NO(2) exposure was associated with adjusted odds ratios of 1.01 (95% CI, 0.83-1.23) for wheeze, 1.10 (95% CI, 0.79-1.51) for severe wheeze, and 1.01 (95% CI, 0.84-1.21) for dry cough. CONCLUSIONS: We were not able to find positive associations of long-term traffic-related exposures with asthma onset or with current respiratory symptoms in 9- to 10-year-old children in Oslo

A Personal Perspective on the Initial Federal Health-Based Regulation to Remove Lead from Gasoline

Objective: This article describes the personal experience and perspective of the authors, who had primary responsibility for drafting the initial health-based regulation limiting lead content of gasoline during the early 1970s while employed by the U.S. Environmental Protection Agency (EPA). Data s o u r c e: Information used by the U.S. EPA in developing the initial health-based regulation limiting lead content of gasoline in December 1973 and studies documenting the impact of that and subsequent actions. Data extraction: Among the lessons learned from this experience is the importance of having input from independent scientists to the regulatory decision-making process. This also demonstrates the critical role of independent peer-reviewed research, such as that supported by the National Institutes of Health, as well as research conducted by scientists from the Centers for Disease Control and Prevention, in delineating the consequences of lead exposure in the population. Data synthesis: Removal of lead from gasoline in the United States has been described as one of the great public health achievements of the 20th century, but it almost did not happen. The experience of the authors in developing this regulation may be helpful to others involved in developing health-based regulatory policy in the future. Co n c l u s i o n: The initial U.S. EPA health-based regulation to remove lead from gasoline is clearly an example where science successfully affected public policy. The leadership of the U.S. EPA at that time deserves much credit for establishing an atmosphere in which this was possible

If Cumulative Risk Assessment Is the Answer, What Is the Question?

Cumulative risk refers to the combined threats from exposure via all relevant routes to multiple stressors including biological, chemical, physical, and psychosocial entities. Cumulative risk assessment is a tool for organizing and analyzing information to examine, characterize, and possibly quantify the combined adverse effects on human health or ecologic resources from multiple environmental stressors. The U.S. Environmental Protection Agency (EPA) has initiated a long-term effort to develop future guidelines for cumulative risk assessment, including publication in 2003 of a framework that describes important features of the process and discusses theoretical issues, technical matters, and key definitions. The framework divides the process of cumulative risk assessment into three interrelated phases: a) planning, scoping, and problem formulation; b) analysis; and c) interpretation and risk characterization. It also discusses the additional complexities introduced by attempts to analyze cumulative risks from multiple stressors and describes some of the theoretical approaches that can be used. The development of guidelines for cumulative risk assessment is an essential element in the transition of the U.S. EPA risk assessment methodology from a narrow focus on a single stressor, end point, source, pathway, and exposure route to a broader, more holistic approach involving analysis of combined effects of cumulative exposure to multiple stressors via all relevant sources, pathways, and routes