As part of the HPV challenge, a project was undertaken to investigate the potential relationship(s) between the polycyclic aromatic compounds (PAC) content of classes of petroleum substances with final boiling points greater than approximately 650 °F and their mammalian toxicity. This investigation focused on the repeated-dose, developmental, reproductive and genetic toxicity endpoints. A secondary objective of the project was to determine whether an association, if it existed, could be used to predict the toxicity of untested petroleum substances. This project specifically evaluated prior work that examined the correlation between the weight percentage of various chemical classes of compounds in thirteen refinery streams and the magnitude of various effects produced in rats treated dermally with these substances in repeat-dose and developmental toxicity studies (Feuston et al. 1994). This 1994 study was evaluated in conjunction with other published literature on the toxicity of individual PAC containing materials, studies sponsored by the American Petroleum Institute (API) and unpublished company laboratory reports.
It was found that there are indeed associations between some repeat-dose and developmental toxicity endpoints and the PAC content of selected petroleum substances. In the repeat-dose toxicity studies, associations were found between the PAC profile and effects on thymus weight, liver weight, hemoglobin concentration and platelet count. In the developmental toxicity studies, associations were found for effects on fetal weight, number of live fetuses/litter and percent resorptions. For each of the endpoints of mammalian toxicity for which an association with PAC content was observed, mathematical models were developed that could be used to make toxicity predictions on the basis of the PAC profile. It should be noted, the models were developed based on observed statistical relationships.
The results of the PAC project showed that predictive models for effects on selected repeat-dose and developmental toxicity endpoints can be developed using the weight percent of each of the 1- through 7-aromatic ring compounds in the test substance, or the “PAC profile”. The effects found to be associated with the PAC profile are consistent with those reported for a number of individual polyaromatic hydrocarbons (PAHs) and PAC-containing materials.
Further information on this PAC project is available in the following documents:
- The peer-reviewed PAC publications that describe the findings of the PAC Project
- A calculator that uses the statistical models to estimate effective dose concentrations of untested petroleum substances
- Instructions for the use of the calculator
- Repeat Dose toxicity data used to build the statistical models
- Developmental toxicity data used to build the statistical models
- Genetic toxicity data used to build model (no calculator for this model)
The primary objective of the Polycyclic Aromatic Compounds (PAC) Project was to investigate the potential relationship(s) between the PAC content of classes of petroleum substances and their human health toxicity. The PAC Analysis Task Group found that predictive models could be developed for selected biological repeat-dose and developmental toxicity endpoints by utilizing the weight percent concentration of each of 7 separate ring classes of aromatic compounds (the ARC profile). The PAC Calculator (containing the underlying equations/predictive models) was developed to calculate the dose associated with a specified change from the control group mean for eight repeated dose and developmental toxicity endpoints in the rat after the dermal application of high boiling petroleum products. The resulting calculated dose is referred to as the Predicted Dose for a Response.
Repeat Dose toxicity data used to build the statistical model can be found here.
Developmental data used to build the statistical models can be found here.
Gene Tox model data can be found here. (No calculator for this model.)
PAC profiles for many HPV Substances can be found here.