RESUMO
An expert panel was assembled to evaluate reproductive toxicology study data and their application to health risk assessment to provide input on the data quality, interpretation, and application of data from three multi-generation reproductive toxicity studies of N-methylpyrrolidone (NMP). Panelists were engaged using a double-blinded, modified Delphi format that consisted of three rounds. Key studies were scored using the U.S. Environmental Protection Agency's (EPA) questions and general considerations to guide the evaluation of experimental animal studies for systematic review. The primary conclusions of the panel are that one of the studies (Exxon, 1991) is not a high-quality study due to several design flaws that includes: (1) exceedance of the maximum tolerable dose in the high dose group; (2) failure to adjust feed concentrations of NMP during the lactation period, resulting in NMP doses that were 2- to 3-fold higher than nominal levels; and/or (3) underlying reproductive performance problems in the strain of rats used. For these reasons, the panel recommended that this study should not be considered for quantitative risk assessment of NMP. Exclusion of this study, and its corresponding data for male fertility and female fecundity, from the quantitative risk assessment results in a change in the identification of the most sensitive endpoint. Instead, changes in rat fetal/pup body weight, an endpoint previously selected by EPA, was identified as an appropriate basis for human health risk assessment based on a consideration of the best available science and weight of scientific evidence supported by the NMP toxicity database.
Assuntos
Pirrolidinonas , Reprodução , Humanos , Ratos , Masculino , Animais , Feminino , Pirrolidinonas/toxicidade , Peso Fetal , Medição de RiscoRESUMO
An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.
Assuntos
Ácidos Alcanossulfônicos , Água Potável , Fluorocarbonos , Água Potável/análise , Fluorocarbonos/análise , Fluorocarbonos/toxicidade , Humanos , Medição de Risco , IncertezaRESUMO
This review is intended to provide risk assessors and risk managers with a better understanding of issues associated with total exposures of human populations to ethylene oxide from endogenous and exogenous pathways. Biomonitoring of human populations and lab animals exposed to ethylene oxide has relied upon the detection of hemoglobin adducts such as 2-hydroxyethylvaline (HEV), which provides a useful measure of total exposure to ethylene oxide from all pathways. Recent biomonitoring data from CDC provide an excellent characterization of total exposure to ethylene oxide to the general U.S. population by demographic factors such as age, gender, and race as well as smoking habit, which might be comparable to previous measurements reported for humans and lab animals. The biochemical pathways including gastrointestinal (production by bacteria) and systemic (enzymatic production) pathways by which endogenous ethylene is generated and converted to ethylene oxide are described. The relative importance of endogenous pathways and exogenous pathways via ambient air or tobacco smoke was quantified based upon available data to characterize their relative importance to total exposure. Considerable variation was noted for HEV measurements in human populations, and important sources of variation for all pathways are discussed. Issues related to risk assessment and risk management of human populations exposed to ethylene oxide are provided within the context of characterizing total exposure, and data needs for supporting future risk assessment identified.
Assuntos
Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Óxido de Etileno/análise , Animais , Exposição Ambiental/efeitos adversos , Óxido de Etileno/efeitos adversos , Feminino , Humanos , Masculino , Medição de Risco/métodos , Fatores de Risco , Gestão de Riscos/métodos , Valina/análogos & derivados , Valina/análiseRESUMO
An approach is presented for ethylene oxide (EO) to derive endogenous equivalent (EE) values, which are endogenous levels normally found within the body expressed in terms of exogenous exposures. EE values can be used to support risk assessment and risk management decisions for chemicals such as EO that have both endogenous and exogenous exposure pathways. EE values were derived using a meta-analysis of data from the published literature characterizing the distribution for an EO biomarker of exposure, hemoglobin N-(2-hydroxyethyl)-valine (HEV), in unexposed populations. These levels are compared to the those reported in exposed populations (smokers, workers). Correlation between the biomarker of exposure and external exposures of EO were applied to this distribution to determine corresponding EE values, which range from 0.13 to 6.9 ppb for EO in air. These values are orders of magnitude higher than risk-based concentration values derived for EO using default methods, and are provided as a pragmatic, data-driven alternative approach to managing the potential risks from exogenous exposures to EO.
Assuntos
Carcinógenos/metabolismo , Carcinógenos/toxicidade , Óxido de Etileno/metabolismo , Óxido de Etileno/toxicidade , Animais , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Humanos , Exposição Ocupacional/efeitos adversos , Medição de Risco/métodos , Gestão de Riscos/métodos , Valina/metabolismo , Valina/toxicidadeRESUMO
A systematic program of sampling and analysis of blood serum for dioxins, furans, and dioxinlike polychlorinated biphenyls (PCBs) has been initiated in the United States through the National Health and Nutrition Examination Survey (NHANES) program. While such data could potentially be used to estimate population-level changes in human milk lipid concentrations of chemicals, such estimates would depend on understanding the relationship between human blood lipid and milk lipid concentrations of the compounds of interest. For dioxins and furans, extremely limited data in humans currently exist for paired blood/milk samples. These data reviewed in this article, support the hypothesis that, over a population and across time, human milk lipid levels of these compounds generally reflect blood lipid levels. However, these data also suggest that significant variations in these ratios are possible among individuals and at various times.
Assuntos
Dioxinas/análise , Furanos/análise , Leite Humano/química , Resíduos de Praguicidas/análise , Bifenilos Policlorados/análise , Dioxinas/sangue , Feminino , Furanos/sangue , Humanos , Lactente , Recém-Nascido , Inquéritos Nutricionais , Bifenilos Policlorados/sangue , Estados UnidosRESUMO
The National Academy of Sciences and many others have noted the need for quantitative health risk assessment methodology that goes beyond a simple screening analysis based on upper bounds on risk. The Academy recommended adoption of methodologies which provide a higher-tier analysis based on realistic estimates of risk which reflect more of the available biological information. In recent years, scientists have challenged the assumption of low-dose linearity and other default assumptions in cancer risk assessment. These challenges have stimulated the continued evolution of quantitative risk assessment methodologies, because effective risk management requires accurate characterizations of uncertainty and greater utilization of cost-benefit analyses for decision making. "Comprehensive Realism" is an emerging quantitative weight-of-evidence based risk assessment methodology for both cancer and noncancer health effects which utilizes probability distributions and decision analysis techniques to reflect more of the available human and animal dose-response data. The current state of knowledge about the relative plausibility of alternative dose-response analyses is also addressed in this approach. The framework discussed here should lead to a higher-tier assessment of butadiene.
Assuntos
Butadienos/toxicidade , Carcinógenos/toxicidade , Medição de Risco , Butadienos/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Modelos BiológicosRESUMO
Geographical theory suggests that consumers will travel to the centre nearest to their residence which offers a particular service. This is a weak indicator of surgery attendance patterns in Gisborne, New Zealand. Nearby surgeries were attended, rather than the nearest available. Various attributes of the practices and the patients were examined to discover their influence on attendance patterns. The distribution of the practices themselves had a significant effect upon relative surgery attendance. Prior knowledge of services was particularly important in determining surgery selection and continued attendance. This accounted for the spatially unconstrained attendance of many Maori. Greater personal mobility enabled higher income households to travel further to attend. Conversely, the less mobile were spatially bounded.