The Use of Hematological Effects in the Development of Minimal Risk Levels
ABSTRACT The Agency for Toxic Substances and Disease Registry (ATSDR) derives minimal risk levels (MRLs) to assist in evaluating risk of adverse health effects in individuals exposed to hazardous substances. MRLs are derived from published values identifying no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) in animal or human studies. The most sensitive end points are used. To date, 4 inhalation MRLs and 13 oral MRLs have been derived from hematological end points for 12 substances. This paper provides a brief overview of the hematological system, examples of hematological end points, and the MRL for substances with hematological end points.
Full-textDOI: · Available from: Henry Abadin, Dec 17, 2013
- SourceAvailable from: Mark Nicolich
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- "Regulatory guidance documents suggest a significant decrease in platelet count would likely be considered an adverse effect (Abadin et al., 1998; ATSDR, 1996, 2006). "
ABSTRACT: A study was undertaken within the context of the U.S. EPA HPV Chemical Challenge Program to 1) characterize relationships between PAC content and repeat-dose toxicities of high-boiling petroleum substances (HBPS) and 2) develop statistical models that could be used to predict the repeat-dose toxicity of similar untested substances. The study evaluated 47 repeat-dose dermal toxicity and 157 chemical compositional studies. The four most sensitive endpoints of repeat-dose toxicity were platelet count, hemoglobin concentration, relative liver weight and thymus weight. Predictive models were developed for the dose-response relationships between the weight percent concentration of each of seven ring classes of aromatic compounds (the "ARC profile") and specific effects, with high correlations (r = 0.91-0.94) between the observed and model-predicted data. The development of the mathematical models used to generate the results reported in this study is described by Nicolich et al. (2013). Model-generated dose-response curves permit the prediction of either the effect at a given dose or the dose that causes a given effect. The models generate values that are consistent with other standard measures. The models, using compositional data, can be used for predicting the repeat-dose toxicity of untested HBPS.Regulatory Toxicology and Pharmacology 06/2013; 67(2). DOI:10.1016/j.yrtph.2013.05.010 · 2.14 Impact Factor
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- "So far, the guidance has served as an internal document. However, parts of the guidance related to neurological, developmental, hematological, and respiratory eVects and the respective MRLs were previously published (Abadin et al., 1998; Chou and Williams-Johnson , 1998; Pohl et al., 1998; Wilbur, 1998). "
ABSTRACT: The Agency for Toxic Substances and Disease Registry (ATSDR) derives health based guidance values called minimal risk levels (MRLs) to assist with assessment of risks posed by exposures to hazardous chemicals. Current MRLs are posted on ATSDR's web site (www.atsdr.cdc.gov). From the total 326 MRLs currently posted, 79 MRLs are based on hepatic endpoints. The paper reports on endpoints used for the derivation of these MRLs and the use of uncertainty factors. It also describes the ranking of effects into less serious and serious categories as described in ATSDR's Guidance for Developing Toxicological Profiles.Regulatory Toxicology and Pharmacology 08/2005; 42(2):161-71. DOI:10.1016/j.yrtph.2005.03.002 · 2.14 Impact Factor
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ABSTRACT: The Agency for Toxic Substances and Disease Registry (ATSDR) derives minimal risk levels (MRLs) for priority hazardous substances. MRLs are health guidance values intended to serve as screening levels for health assessors to select contaminants of concern and to assess potential health effects at hazardous waste sites and areas affected by unplanned releases. Current MRLs are published in ATSDR toxicological profiles and are listed at the ATSDR website at . To date, ATSDR has derived 125 inhalation MRLs, 207 oral MRLs, and eight external radiation MRLs; 19 MRLs are based on renal effects. This article reports on endpoints used to derive the MRLs. It also presents the ranking of effects into less serious and serious categories as described in ATSDR's Guidance for Developing Toxicological Profiles.Regulatory Toxicology and Pharmacology 08/2005; 42(2):202-8. DOI:10.1016/j.yrtph.2005.04.003 · 2.14 Impact Factor