title: The relationship between repeat-dose toxicity and aromatic-ring class profile of high-boiling petroleum substances.
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 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.
authors.affiliation: Roth Toxicology Consulting, P.O. Box 6023, Thousand Oaks, CA 91359, USA. Electronic address: rroth@rothtox.com.
authors.forename: Randy N
authors.initials: RN
authors.lastname: Roth
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Simpson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Nicolich
authors.forename: F Jay
authors.initials: FJ
authors.lastname: Murray
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Gray
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015233:Models, Statistical; D010578:Petroleum / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000633:toxicity*; D036401:Toxicity Tests, Chronic; D059551:Toxicity Tests, Subacute; D044366:Transition Temperature
chemical_list: D010578:Petroleum; D011084:Polycyclic Aromatic Hydrocarbons
keywords: Biological models; Dermal; HPV chemical challenge program; High-boiling petroleum substances; Mixtures toxicity; Polycyclic aromatic compounds; QCAR modeling; Rat; Repeat-dose toxicity