Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2592311 | Regulatory Toxicology and Pharmacology | 2013 | 16 Pages |
•Modeled thymus weight, liver weight, hemoglobin concentration and platelet count.•Models based on data from 18 dermal repeat-dose toxicity studies in rats of HBPS.•Associations between wt.% of aromatic-ring classes 1–7 and endpoint effects.•High correlation between model-predicted and observed responses.•High agreement between modeled values and values determined using existing methods.
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 wt.% 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.