Superfund Research Program
PAHs in Humans at Environmental Levels: Pharmacokinetics, Metabolism and Susceptible Individuals
Project Leader: David E. Williams
Grant Number: P42ES016465
Funding Period: 2013-2020
In order to conduct the first pharmacokinetic study of benzo[a]pyrene (BaP) in humans, the research team established a rigorous UHPLC system to separate BaP metabolites from the parent compound. The team was then able to follow the uptake and elimination rates of each metabolite with the UHPLC-AMS instrument. This represents the first dataset of the metabolic profile of BaP in humans at ultra-low dose and can be used for more accurate risk assessment from common dietary exposures. The research team also conducted the first evaluation of the Relative Potency Factor (RPF) approach to risk assessment for PAHs in human studies. Volunteers consuming smoked salmon containing 10 times the BaPeq , as determined by the RPF, exhibited a marked alteration in the degree of BaP metabolism, metabolic profile, and elimination rates. This data will be useful to the Environmental Protection Agency (EPA) as the move forward with risk assessment models for consumption of PAHs in the diet, such as fish from the Gulf of Mexico. In addition, the research team conducted the first assessment of gene-environment interactions in humans at environmentally relevant levels of exposure to PAHs. BaP is bioactivated to the ultimate carcinogenic metabolite by cytochrome P450 (CYP) 1B1. Om genotyping individuals, the research team demonstrated that, compared to wild-type CYP1B1, the common CYP1B1*3/*3 variant resulted in a significant change in the metabolic profile of BaP. This data, though limited, if studied further could establish the most susceptible individuals in the population.