BIOCHEMICAL EFFECTS OF MANUFACTURED-GAS PLANT RESIDUE FOLLOWING INGESTION BY B6C3F1 MICE

The toxic potential of manufactured gas plant residue (MGP) given in t he diet to male and female B6C3F1 mice was evaluated. In addition, the bioavailability of chemical components of MGP were also investigated by monitoring polycylic aromatic hydrocarbon (PAH) metabolites in urin e and DNA adduct formation in forestomach and lung tissue. Basal gel d iets containing 0.05, 0.25, 0.50% MGP or 0.005% benzo[a]pyrene (BaP) w ere fed to animals for 94 and 185 d. Mice readily consumed adulterated diets without any evidence of acute toxicity. The total amount of MGP and BaP consumed by mice ranged from 118 to 2604 mg and from 12 to 29 mg, respectively. Male mice fed a control or BaP diet and female mice fed a 0.05% MGP diet had the highest body weight gains. Male and fema le mice fed a 0.50% MGP diet had the lowest body weight gains. The bio availability of chemical components of MGP was evaluated by monitoring the urinary excretion of PAH metabolites by male mice fed a 0.25% MGP diet. 1-Hydroxypyrene was determined by high-performance liquid chrom atography analysis to be the major fluorescent metabolite excreted by mice throughout the 185 d of diet administration. At necropsy, no chem ical-related gross lesions were detected. In addition, no treatment-re lated microscopic lesions were evident in tissues obtained from animal s fed a 0.50% MGP- or BaP-adulterated diet: The P-32-postlabeling assa y was used to evaluate MGP- and BaP-induced DNA adduct formation in lu ng and forestomach tissue. The level of DNA adducts formed from the ch emical components of MGP paralleled the amount of material ingested by animals. Lung DNA adduct levels were considerably higher than foresto mach levels when mice ingested a 0.25% or 0.50% MGP diet. These studie s demonstrate that the continuous ingestion of MGP or BaP for 185 d do es not result in acute toxicity or chemical-related lesions at doses u p to 0.50% MGP or 0.005% BaP.