The development of acute exposure guideline levels for hazardous substances.
ABSTRACT The National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL) was created to develop guideline levels for short-term exposures to airborne concentrations for approximately 400-500 high priority, acutely hazardous substances. The program should be completed within the next 10 years. These Acute Exposure Guideline Levels (AEGLs) are being applied to a wide range of planning, response, and prevention applications both within the United States and abroad. The NAC/AEGL Committee seeks to develop the most scientifically credible, acute (short-term) exposure guideline levels possible within the constraints of data availability, resources and time. The program begins with comprehensive data gathering, data evaluation and data summarization. The resulting Technical Support Documents (TSD) are first reviewed by a small review committee; (chemical manager, two chemical reviewers and the author), then by the full AEGL committee. After that review, a summary is published in the Federal Register for Public comment. When these comments have been addressed, the TSDs are sent to the National Research Council's (NRC) Subcommittee on AEGLs for a peer review. Following acceptance by the NRC, they are published by the Academy. The NAC/AEGL Committee currently comprises representatives of federal, state, and local agencies and representatives from France, Germany, and the Netherlands, private industry, medicine, academia and other organizations in the private sector that will derive programmatic or operational benefits from the existence of the AEGL values. AEGL values are determined for three different health effect end-points. These values are intended for the general public where they are applicable to emergency (accidental) situations. Threshold exposure values are developed for five exposure periods (10 and 30 min, 1 h, 4 h, 8 h). Each threshold value is distinguished by varying degrees of severity of toxic effects, as initially conceived by the American Industrial Hygiene Association's Emergency Response Planning Committee, subsequently defined in the NAS' National Research Council publication of the Guideline for Developing Community Emergency Exposure Levels for Hazardous Substances and further categorized in the Standing Operating Procedures of the NAC/AEGL Committee. To date, the committee has reviewed almost 100 chemicals.
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ABSTRACT: Emergency preparedness personnel at U. S. Department of Energy (DOE) facilities use the chemical mixture methodology (CMM) to estimate the potential health impacts to workers and the public from the unintended airborne release of chemical mixtures. The CMM uses a Hazard Index (HI) for each chemical in a mixture to compare a chemical's concentration at a receptor location to an appropriate concentration limit for that chemical. This limit is typically based on Protection Action Criteria (PAC) values developed and published by the DOE. As a first cut, the CMM sums the HIs for all the chemicals in a mixture to conservatively estimate their combined health impact. A cumulative HI>1.0 represents a concentration exceeding the concentration limit and indicates the potential for adverse health effects. Next, Health Code Numbers (HCNs) are used to identify the target organ systems that may be impacted by exposure to each chemical in a mixture. The sum of the HIs for the maximally impacted target organ system is used to provide a refined, though still conservative, estimate of the potential for adverse health effects from exposure to the chemical mixture. This paper explores approaches to enhance the effectiveness of the CMM by using HCN weighting factors. A series of 24 case studies have been defined to evaluate both the existing CMM and three new approaches for improving the CMM. The first approach uses a set of HCN weighting factors that are applied based on the priority ranking of the HCNs for each chemical. The second approach uses weighting factors based on the priority rankings of the HCNs established for a given type of concentration limit. The third approach uses weighting factors that are based on the exposure route used to derive PAC values and a priority ranking of the HCNs (the same ranking as used in the second approach). Initial testing indicates that applying weighting factors increases the effectiveness of the CMM chemical mixtures in general, though care must be taken to avoid introducing non-conservative results. In the near future, additional testing and analysis will be conducted that may lead to the adoption of one of the tested approaches into the CMM.Toxicology 11/2012; · 3.75 Impact Factor
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ABSTRACT: The kinetics of sorption of micromolecular swelling agents by polymeric media often deviates from normal Fickian behavior in various ways, which have to be understood and interpreted, with the aid of appropriate models, in terms of the underlying physics. One difficulty which arises in this respect is that salient aspects of the observed kinetic behavior can be mimicked by extraneous effects, in the form of significant deviation from a boundary condition or of imperfect macroscopic homogeneity of the polymer film (modeled in both cases as a surface resistance to penetrant transport). Such effects have, in fact, been invoked (notably by Hansen (2010) ) to question the significance of conclusions drawn from modeling approaches based on the effect of intrinsic bulk polymer properties, leading to delayed (viscous) swelling and to build-up and decay of differential swelling stresses. We present here a brief critical account (following the mainstream modeling line initiated by Crank) of typical results concerning various salient aspects of observed non-Fickian sorption kinetics and of the comparative possibility of achieving satisfactory general interpretation thereof, in terms of approaches based on the aforementioned extraneous, versus intrinsic bulk property, effects. We find that the latter approach has been successful so far, both computationally and physically, by establishing a close physically significant analogy between non-Fickian sorption, and (both linear and non-linear) viscoelastic mechanical deformation, behavior. The former approach, on the other hand, proves weak on both counts.European Polymer Journal 11/2011; 47(11):2053-2062. · 3.24 Impact Factor
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ABSTRACT: A simple method is presented for estimating a non-lethal level for inhalation toxicity studies. By reviewing 209 LC50 studies representing 96 chemicals that also reported a non-lethal level, it has been shown that taking 1/3 of the LC50 is a conservative estimate for a non-lethal exposure level. This approach was also compared to studies with LC01 and BMCL05 calculations. In the 38 studies that reported either of these values, again taking 1/3 of the LC50 provided a more conservation estimate for the non-lethal threshold. The studies included time intervals from 5 min out to 8 h and utilized multiple species such as the rat, mouse, hamster, guinea pig and dog. In all but 13 cases, taking 1/3 of the LC50 provided a more conservative estimate for a non-lethal exposure level compared to the experimentally observed value. In all but one of the 13 cases, the higher values were consequences of the selection of the exposure levels.Regulatory Toxicology and Pharmacology 08/2009; · 2.14 Impact Factor