Pharmacokinetic studies, isolation and identification of metabolites of benz(a)acridine in rats

Benz(a)acridine (BaAc) is a nitrogen-containing polyaromatic compound (N-PAC) present in coal-derived complex mixtures (CDCM) that are formed during the process of coal liquefaction in the production of synthetic fuels. Occupational exposure of synfuel workers causes concern about potential carcinogenicity of this class of chemicals, and animal experimental data on their pharmacokinetics and metabolic fate are needed for risk evaluation.;;Rats excreted 63-66% of the dose in feces; 90% of the fecal radioactivity was in form of unconjugated metabolites, and 10% was conjugated. A diphenol, a triol epoxide and a tetrol were identified in addition to the metabolites obtained from incubation in vitro. 34-37% of the dose was excreted in urine, predominantly as conjugates. Glucuronides ranged from 33-36% and sulfates from 18-29% of the urinary metabolites. Two pentaols were identified as unconjugated urinary metabolites. The results of these studies show that BaAc is absorbed through the skin, metabolized to a variety of hydroxylated products and eliminated as free or conjugated metabolites by urinary and fecal excretion. Coadministration of other N-PAC compounds as complex mixture slows both the absorption and the metabolisation of BaAc. It is therefore to be expected that under conditions of occupational exposure the biological effects of BaAc and other components of coal-derived complex mixtures will be less than additive.