Journal
REGULATORY TOXICOLOGY AND PHARMACOLOGY
Volume 67, Issue 2, Pages S46-S59Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yrtph.2013.05.003
Keywords
Biological models; Dermal; Developmental toxicity; High-boiling petroleum substances; HPV Challenge Program; Mixtures toxicity; Polycyclic aromatic compounds; QCAR modeling; Rat; UVCB
Categories
Funding
- Petroleum High Production Volume Testing Group
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In response to the US EPA HPV Challenge Program, this study was conducted to: (1) evaluate the relationship between PAC content and the developmental toxicity of high-boiling petroleum substances (HBPS) and (2) develop mathematical models to predict the developmental toxicity of similar untested substances based on their aromatic ring class (ARC) profiles. For this investigation, 68 developmental toxicity studies were reviewed. The ARC models relied on data from 21 rat dermal developmental toxicity studies conducted with similar experimental designs to ensure a consistent data set for comparison. The most sensitive general endpoints of developmental toxicity (i.e., decreased fetal survival and growth) were chosen for modeling. The ARC models demonstrated a strong correlation between the predicted vs. observed values for specific sensitive endpoints of these developmental toxicities (percent resorptions, r = 0.99; live fetuses per litter, r = 0.98; fetal body weight, r = 0.94). Such associations provide a promising approach for predicting the developmental toxicity of untested HBPS. Efforts to corroborate the ARC models using test substances that were not used to build the ARC models produced mixed results, and further development and refinement of the ARC models is recommended before they can be reliably applied to all HBPS. (C) 2013 Elsevier Inc. All rights reserved.
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