Search

The purpose of this article is to review and interpret the scientific literature on the mammalian toxicity of ethylene glycol (EG) and propylene glycol (PG), with the goal of comparing the toxicity of the two chemicals. This type of review may serve as the basis for risk management decision-making. Because EG is not a GRAS (generally recognized as safe) chemical, its uses are restricted when compared with PG; thus, certain routes of exposure are not relevant here for toxicological comparison (e.g., subcutaneous, intramuscular, and intravenous). Therefore, this review is focused on the oral, inhalation, and dermalroutes of exposure. However, where toxicological data derived from an alternative route of exposure serve to eludicate mechanisms of toxicity, data from these routes are considered. Based on the review provided herein, the following conclusions can be drawn. From the standpoint of lethality, acute effects, and reproductive, developmental, andkidney toxicity, the toxicity of EG exceeds that of PG. Further, localized dermal effects from EG and PG are both mild, with data suggesting that PG may have a skin contact sensitization potential. Finally,PG exposure in laboratory animals has been associated with reversible hematological changes; no data were located for EG from which to draw a toxicological comparison. [ABSTRACT FROM AUTHOR]

Traditionally, regulatory approaches to the bioaccumulation of hydrophobic organic chemicals (HOCs) have emphasized the direct accumulation of these chemicals from solution across biological membranes, leading to the development of the bioconcentration factor as a measure ofdirect uptake of freely dissolved HOCs. However, an often larger fraction of the total amount of many HOCs in the water column is not freely dissolved, but is partitioned among suspended sediments and particulate matter in the water column. Partitioned HOCs are available foraccumulation by organisms ingesting the contaminated particulate matter. The net accumulation of HOCs from water through consumption and direct uptake of dissolved HOC is termed bioaccumulation, quantified using a bioaccumulation factor. In order to develop recommendations designed to close the gap between current knowledge concerning bioaccumulation and regulations, the Institute of Evaluating Health Risks organized a working conference, 'The Bioaccumulation of Hydrophobic Organic Chemicals by Aquatic Organisms'. This paper reflects the view ofworkshop participants that the bioaccumulation paradigm can be used in a number of practical applications. [ABSTRACT FROM AUTHOR]

Air pollution accountability studies examine the relationship(s) between an intervention, regulation, or event and the resulting downstream impacts, if any, on emissions, exposure, and/or health. The sequence of events has been schematically described as an accountability chain. Here, we update the existing framework to capture real-life complexities and to highlight important factors that fall outside the linear chain. This new "accountability web" is intended to convey the intricacies associated with conducting an accountability study to various audiences, including researchers, policy makers, and stakeholders. We also identify data considerations for planning and completing a robust accountability study, including those relevant to novel and innovative air pollution and exposure data. Finally, we present a series of recommendations for the accountability research community that can serve as a guide for the next generation of accountability studies., Competing Interests: Support for the Workshop was provided by the 10.13039/100011253American Petroleum Institute (API). API was not involved in the Workshop deliberations nor in the preparation or approval of the manuscript. The authors retain sole responsibility for the writing and content of this paper, which represent the professional opinions of the authors and not necessarily those of API or its member companies. As Workshop facilitators, CJB, JEG, and JSL received compensation and travel support from 10.13039/100011253API. Travel support was also provided to all authors except AMR, HSE, and SL. Honoraria were provided to SE, LRFH, MN, AGR, and JWH. JSL, JEG, JWH, and CJB consult to governmental and private organizations, including API, on issues related to air pollution epidemiology. The views expressed in this manuscript are those of the authors and do not necessarily represent the views or policies of EPA, API (or its member companies), or co-authors' employers., (© 2023 The Authors. Published by Elsevier Inc.)

Objectives: The objective of the study is to present the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) conceptual approach to the assessment of certainty of evidence from modeling studies (i.e., certainty associated with model outputs)., Study Design and Setting: Expert consultations and an international multidisciplinary workshop informed development of a conceptual approach to assessing the certainty of evidence from models within the context of systematic reviews, health technology assessments, and health care decisions. The discussions also clarified selected concepts and terminology used in the GRADE approach and by the modeling community. Feedback from experts in a broad range of modeling and health care disciplines addressed the content validity of the approach., Results: Workshop participants agreed that the domains determining the certainty of evidence previously identified in the GRADE approach (risk of bias, indirectness, inconsistency, imprecision, reporting bias, magnitude of an effect, dose-response relation, and the direction of residual confounding) also apply when assessing the certainty of evidence from models. The assessment depends on the nature of model inputs and the model itself and on whether one is evaluating evidence from a single model or multiple models. We propose a framework for selecting the best available evidence from models: 1) developing de novo, a model specific to the situation of interest, 2) identifying an existing model, the outputs of which provide the highest certainty evidence for the situation of interest, either "off-the-shelf" or after adaptation, and 3) using outputs from multiple models. We also present a summary of preferred terminology to facilitate communication among modeling and health care disciplines., Conclusion: This conceptual GRADE approach provides a framework for using evidence from models in health decision-making and the assessment of certainty of evidence from a model or models. The GRADE Working Group and the modeling community are currently developing the detailed methods and related guidance for assessing specific domains determining the certainty of evidence from models across health care-related disciplines (e.g., therapeutic decision-making, toxicology, environmental health, and health economics)., (Copyright © 2020. Published by Elsevier Inc.)

A clear picture of ranges of doses of breast-milk contaminants experienced by nursing infants in North America has not yet been described, resulting in a significant gap in our understanding of potential health risks to infants from those contaminants. While point estimates of incremental dose have appeared in the published literature, these do not account for the wide variability in exposures experienced by nursing infants. This research expands on the current state of understanding of breast-milk contaminant exposure by characterizing distributions, rather than point estimates, of dose. Distributions of milk intake by nursing infants were characterized to examine intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and dichlorodiphenyl dichloroethane (DDE). The results indicate that, despite the uncertainties inherent in modeling incremental body burdens of chemicals from nursing, estimating incremental infant body burdens of lipophilic chemicals from breastfeeding using point estimates may result in overly conservative estimates of the contribution of breastfeeding to long-term body burdens of those chemicals in children. To develop reliable estimates of incremental body burden from nursing, depuration via lactation and half-life in the infant should be considered. Further, incremental infant body burdens of lipophilic chemicals increase rapidly at the start of lactation, but decrease after approximately 5 to 6 mo; by 2 yr postpartum, incremental body burdens have decreased substantially. Given the benefits afforded to infants who breastfeed, and because breastfeeding does not necessarily lead to significantly increased long-term body burdens in infants, breastfeeding should be encouraged and promoted.

The 16-City Study analyzed for gas-phase environmental tobacco smoke (ETS) constituents (nicotine, 3-ethenyl pyridine [3-EP], and myosmine) and for particulate-phase constituents (respirable particulate matter [RSP], ultraviolet-absorbing particulate matter [UVPM], fluorescing particulate matter [FPM], scopoletin, and solanesol). In this second of three articles, we discuss the merits of each constituent as a marker for ETS and report pair-wise comparisons of the markers. Neither nicotine nor UVPM were good predictors for RSP. However, nicotine and UVPM were good qualitative predictors of each other. Nicotine was correlated with other gas-phase constituents. Comparisons between UVPM and other particulate-phase constituents were performed. Its relation with FPM was excellent, with UVPM approximately 1 1/2 times FPM. The correlation between UVPM and solanesol was good, but the relationship between the two was not linear. The relation between UVPM and scopoletin was not good, largely because of noise in the scopoletin measures around its limit of detection. We considered the relation between nicotine and saliva continine, a metabolite of nicotine. The two were highly correlated on the group level. That is, for each cell (smoking home and work, smoking home but nonsmoking work, and so forth), there was high correlation between average continine and 24-hour time-weighted average (TWA) nicotine concentrations. However, on the individual level, the correlations, although significant, were not biologically meaningful. A consideration of cotinine and nicotine or 3-EP on a subset of the study whose only exposure to ETS was exclusively at work or exclusively at home showed that home exposure was a more important source of ETS than work exposure.

The ultimate goal of the research reported in this series of three articles is to derive distributions of doses of selected environmental tobacco smoke (ETS)-related chemicals for nonsmoking workers. This analysis uses data from the 16-City Study collected with personal monitors over the course of one workday in workplaces where smoking occurred. In this article, we describe distributions of ETS chemical concentrations and the characteristics of those distributions (e.g., whether the distribution was log normal for a given constituent) for the workplace exposure. Next, we present population parameters relevant for estimating dose distributions and the methods used for estimating those dose distributions. Finally, we derive distributions of doses of selected ETS-related constituents obtained in the workplace for people in smoking work environments. Estimating dose distributions provided information beyond the usual point estimate of dose and showed that the preponderance of individuals exposed to ETS in the workplace were exposed at the low end of the dose distribution curve. The results of this analysis include estimations of hourly maxima and time-weighted average (TWA) doses of nicotine from workplace exposures to ETS (extrapolated from 1 day to 1 week) and doses derived from modeled lung burdens of ultraviolet-absorbing particulate matter (UVPM) and solanesol resulting from workplace exposures to ETS (extrapolated from 1 day to 1 year).

Concentrating on exposure in workplaces where smoking occurs, we examined environmental tobacco smoke (ETS)-related concentration data from the 16-City Study. This study involved a large population of nonsmokers, used personal monitors, and encompassed a wide selection of ETS-related constituents. This first article in a series of three describes the 16-City Study, considers the impact of demographic variables, and concludes that these variables did not explain differences in exposure to ETS. We compared 16-City Study concentrations obtained in the workplace to previously reported workplace concentrations and determined that data from this study were representative of current ETS exposure in nonmanufacturing workplaces where smoking occurs. Considering factors other than demographic factors, we found that, not surprisingly, the number of cigarettes observed in the workplace had an impact on exposure concentrations. Finally, we compared people from homes where smoking occurs with people from nonsmoking homes and found that people from smoking homes observed more smoking in the workplace and experienced higher concentrations of ETS-related compounds in the workplace, even when they observed the same number of cigarettes being smoked in the workplace. In two subsequent articles in this series, we discuss relationships between various ETS markers and provide estimates of distributions of doses to nonsmoking workers employed in workplaces where smoking occurs.

A threshold blood lead level in children below which no adverse effects occur has not been identified (CDC, 1991), Therefore, the traditional risk assessment method of relating dose to a reference dose (RfD) for noncancer effects is not applicable to lead. To assess whether environmental lead concentrations may result in adverse health effects, predicted blood lead levels are compared to a blood lead level of 10 micrograms/dL, the current Centers for Disease Control and Prevention level of concern. Children's blood lead levels may be predicted with one of at least three models: USEPA'S Integrated Exposure Uptake Biokinetic Model (IEUBK), and models by O'Flaherty (1993) and Carlisle and Wade (1992). This paper explores the utility of these models for predicting blood lead levels in children, and discusses areas of uncertainty associated with the use of these models in evaluating episodic exposures. It is hoped that this discussion will stimulate interest further researching exposure and health effects from episodic contact with lead contaminated media.

Human exposure to many pollutants occurs primarily through the ingestion of contaminated fish. In order to protect human health, regulatory agencies set limits on the levels of pollutants entering water bodies from point sources, thereby limiting the amount of pollutants that may be accumulated by fish. The limits, in the form of water quality criteria, are designed to correlate the concentration of a pollutant in a water body (and therefore the concentration accumulated by a fish) to the risks to humans. This type of model provides a reasonable way of controlling pollutants from point sources if the assumptions used in the model are realistic. However, the risk assessment formula currently used for developing water quality criteria only considers those pollutants in the water column available to fish through bioconcentration across the gills (freely dissolved pollutants). For strongly hydrophobic pollutants like dioxin, an extremely small fraction of the total amount is freely dissolved; most dioxin is sorbed to organic matter and is ingested by fish. A new model for developing criteria is presented here that takes into account the environmental fate of dioxin (predominantly in the sorbed state in the environment) and that fish accumulate dioxin by ingestion, rather than bioconcentration.