The development of statistical models to determine the relationship between aromatic-ring class profile and repeat-dose and developmental toxicities of high-boiling petroleum substances

Autor: Mark J. Nicolich, F. Jay Murray, Thomas M. Gray, Randy N. Roth, Barry J. Simpson
Rok vydání: 2013
Předmět:
Zdroj: Regulatory Toxicology and Pharmacology. 67:S10-S29
ISSN: 0273-2300
Popis: The repeat-dose and developmental toxicities of certain petroleum refinery streams are related to their polycyclic aromatic compound (PAC) content ( Feuston et al., 1994 ). Building on this foundation, and working within the context of the US EPA High Production Volume (HPV) Chemical Challenge Program, we: (1) characterized relationships between PAC content and repeat-dose and developmental toxicities of high boiling petroleum substances (HBPS), and (2) developed statistical models that can be used to predict critical effects of similar untested substances. Data from 39 dermal toxicity studies of HBPS were used to develop statistical models to predict the dose–response relationships between the weight percent concentration of each of their 1–7 aromatic ring classes and 4 repeat-dose and 3 developmental endpoints (absolute thymus weight, hemoglobin count, platelet count, liver to body weight, live fetus count, fetal weight, and percent resorptions). The correlations between the observed and model-predicted values are >0.90. The predictive ability of the models was tested via a series of evaluation or corroboration methods. As is shown in the paper, using only compositional data of untested HBPS, the models can be used to predict the effect at a given dose or the dose that causes an effect of a stipulated magnitude.
Databáze: OpenAIRE