Abstract  The results of dermal absorption experiments are routinely and often exclusively reported in terms of fractional absorption. However, fractional absorption is not generally independent of skin loading conditions. As a consequence, experimental outcomes are commonly misinterpreted. This can lead in turn to poor estimation of exposures under field conditions and inadequate threat assessment. To aid interpretation of dermal absorption-related phenomena, a dimensionless group representing the ratio of mass delivery to plausible absorptive flux under experimental or environmental conditions is proposed. High values of the dimensionless dermal number (N(DERM)) connote surplus supply (i.e., flux-limited) conditions. Under such conditions, fractional absorption will generally depend on load and should not be assumed transferable to other conditions. At low values of N(DERM), dermal absorption will be delivery-limited. Under those conditions, high fractional absorption is feasible barring maldistribution or depletion due to volatilization, washing, mechanical abrasion or other means. Similar logic also applies to skin sampling and dermal toxicity testing. Skin surface sampling at low N(DERM) is unlikely to provide an appropriate measure of potential dermal dose due to depletion, whereas dermal toxicity testing at high N(DERM) is unlikely to show dose dependence due to saturation.

Abstract  The Guidelines for Exposure Assessment describe the general concepts of exposure assessment including definitions and associated units, and by providing guidance on the planning and conducting of an exposure assessment. Guidance is also provided on presenting the results of the exposure assessment and characterizing uncertainty. Although these Guidelines focus on exposures of humans to chemical substances, much of the guidance also pertains to assessing wildlife exposure to chemicals, or human exposures to biological, noise, or radiological agents. The Guidelines include a glossary which helps standardize terminology used by the Agency in exposure assessment. They emphasize that exposure assessments done as part of a risk assessment need to consider the hazard identification and dose-response parts of the risk assessment in the planning stages of the exposure assessment so that these three parts can be smoothly integrated into the risk characterization. The Guidelines discuss and reference a number of approaches and tools for exposure assessment, along with discussion of their appropriate use. The Guidelines also stress that exposure estimates along with supporting information will be fully presented in Agency risk assessment documents, and that Agency scientists will identify the strengths and weaknesses of each assessment by describing uncertainties, assumptions, and limitations, as well as the scientific basis and rationale for each assessment.

Abstract  This report is one of a series of publications, The Quality of Our Nation’s Waters, that describe major findings of the National Water-Quality Assessment (NAWQA) Program on water-quality issues of national and regional concern. This report is on volatile organic compounds (VOCs) in ground water and drinking-water supply wells. It is a synthesis of NAWQA and other investigations. Fifty-five VOCs are emphasized in NAWQA’s field studies, and these compounds are the focus of this report. During NAWQA’s first decade of Study-Unit investigations, samples from more than 2,500 wells were analyzed for VOCs. In addition, carefully selected VOC data from more than 1,700 well samples were compiled from other agencies or collected in other USGS studies. Collectively, these VOC analyses are the basis for this report’s assessment, which is (1) the first national assessment of a large number of VOCs in the Nation’s aquifers and (2) the most recent national characterization of VOCs in samples from domestic and public wells used for drinking water.

Abstract  EPA has released a final report entitled, A Framework for Assessing Health Risk of Environmental Exposures to Children, which examines the impact of potential exposures during developmental lifestages and subsequent lifestages, while emphasizing the iterative nature of the analysis phase with a multidisciplinary team. Major findings and conclusions: This report outlines the framework in which mode of action(s) (MOA) can be considered across life stages. The framework is based upon existing approaches adopted in the Framework on Cumulative Risk Assessment and identifies existing guidance, guidelines and policy papers that relate to children's health risk assessment. It emphasizes the importance of an iterative approach between hazard, dose response, and exposure analyses. In addition, it includes discussion of principles for weight of evidence consideration across life stages for the hazard characterization database. Key science/assessment issues:This framework addresses the questions of why and how an improved children's health risk assessment will strengthen the overall risk assessment process across the Agency. This approach improves the scientific explanation of children's risk and will add value by: 1) providing for a more complete evaluation of the potential for vulnerability at different life stages, including a focus on the underlying biological events and critical developmental periods for incorporating MOA considerations; 2) evaluating of the potential for toxicity after exposure during all developmental life stages; and 3) integrating of adverse health effects and exposure information across life stages.

Abstract  This volume covers the solubilities of halogenated ethanes and ethenes with water, heavy water, seawater, and aqueous electrolyte solutions. All data were critically examined for their reliability and best value estimates were selected on the basis of such evaluations. Referenced works are presented in the standard IUPAC-NIST Solubility Data Series format. Reported and best value data are presented in tabular form and, where justified, data correlation equations and graphical illustrations are provided. Throughout the volume, SI conventions have been employed as the customary units. The importance of these data arises from the fact that halogenated ethanes and ethenes have commercial uses as industrial chemicals, propellants, solvents, and the like. In such applications, often from spillage, leakage, or mishandling, they contact water and are exposed to the atmosphere. The data are essential for concentration estimates for the halogenated ethanes and ethenes in drinking and ground water, foodstuffs, human tissue, marine organisms, and the atmosphere. The halogenated aliphatics are of particular interest to health scientists, engineers, environmentalists, and atmospheric chemists in that they represent a class of chemical materials which has many significant industrial applications. However, at the same time, these substances have been shown, in some cases, to be carcinogenic and also to be especially damaging to the earth’s atmospheric composition through their chemical reactivity which results in atmospheric ozone depletion. The high ozone depletion potentials of this class of chemical substances emphasizes the importance of having available complete, accurate, and reliable data for mutual solubilities with water. The availability of such data is essential for estimates of halogenated hydrocarbon levels in both natural waters and aqueous industrial liquids which result from industrial fabrication, industrial waste removal processes, and the like. The data also provide significant solubility values for studies concerning the health of human and other biological systems.

Abstract  Although epidemiology studies have associated maternal trichloroethylene (TCE) exposure with decreased birth weight and preterm birth, mechanistic explanations for these associations are currently lacking. We hypothesized that TCE targets the placenta with adverse consequences for pregnancy outcomes. Pregnant Wistar rats were exposed orally to vehicle or 480 mg TCE/kg body weight from gestational days (gd) 6-16, and tissues were collected on gd 16. Exposure to TCE significantly decreased average fetal weight without reducing maternal weight. In placenta, TCE significantly increased 8-hydroxy-deoxyguanosine, global 5-hydroxymethylcytosine, and mRNA expression of Tet3, which codes for an enzyme involved in 5-hydroxymethylcytosine formation. Furthermore, glutathione S-transferase activity and immunohistochemical staining were increased in placentas of TCE-exposed rats. The present study provides the first evidence that TCE increases markers of oxidative stress in placenta in a fetal growth restriction rat model, providing new insight into the placenta as a potentially relevant target for TCE-induced adverse pregnancy outcomes.

Abstract  There is substantial potential for human exposure to trichloroethylene (TCE), as it has a widespread presence in ambient air, indoor air, soil, and groundwater. At the same time, humans are likely to be exposed to a variety of compounds that are either metabolites of TCE or which have common metabolites or targets of toxicity. Once exposed, humans, as well as laboratory animal species, rapidly absorb TCE, which is then distributed to tissues via systemic circulation, extensively metabolized, and then excreted primarily in breath as unchanged TCE or carbon dioxide, or in urine as metabolites. The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to trichloroethylene. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of trichloroethylene