Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice

Abstract

The toxic potential of manufactured gas plant residue (MGP) given in the diet to male and female B6C3F1 mice was evaluated. In addition, the bioavailability of chemical components of MGP were also investigated by monitoring polycyclic aromatic hydrocarbon (PAH) metabolites in urine and DNA adduct formation in forestomach and lung tissue. Basal gel diets containing 0.05, 0.25, 0.50% MGP or 0.005% benzo[a]pyrene (BaP) were 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 female mice fed a 0.50% MGP diet had the lowest body weight gains. The bioavailability 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 chromatography analysis to be the major fluorescent metabolite excreted by mice throughout the 185 d of diet administration. At necropsy, no chemical-related gross lesions were detected. In addition, no treatment-related microscopic lesions were evident in tissues obtained from animals fed a 0.50% MGP- or BaP-adulterated diet. The 32P-postlabeling assay was used to evaluate MGP- and BaP-induced DNA adduct formation in lung and forestomach tissue. The level of DNA adducts formed from the chemical components of MGP paralleled the amount of material ingested by animals. Lung DNA adduct levels were considerably higher than forestomach levels when mice ingested a 0.25% or 0.50% MGP diet. These studies demonstrate that the continuous ingestion of MGP or BaP for 185 d does not result in acute toxicity or chemical-related lesions at doses up to 0.50% MGP or 0.005% BaP.

Evaluation of PAH: DNA Adduct Formation in Rats Fed Coal Tar-Contaminated Diets

“…The slight aversion to tar and extract diets is notably different than that observed with mice and may be associated with the odor associated with these diets. Previous studies demonstrated that mice would easily accommodate up to 0.5% coal tar in diets for 185 days of feeding (13). Thus, rats appear to be less tolerant to neat coal tar material when compared with mice, which could reduce the amount that can be administered to rats in short-and long-term studies.…”

“…A comparison of values observed with "tar" and "extract" diets indicates a PAH relative bioavailability of 65% (13).…”

“…The dose-adjusted excretion values (amount of 1-OH pyrene excreted/amount of pyrene ingested over 24 hr) were determined to be 1.29, 1.63, and 1.85. Values obtained with animals fed soil and extract can be further compared (soil/ extract; 1.63/1.85) to estimate a PAH relative bioavailability value of 88% (13).…”

Diesel Exhaust Affects the Abnormal Delivery in Pregnant Mice and the Growth of Their Young

“…Therefore, the changes in body weight in young mice may be a result of the complex effects of differences in milk composition, nursing behavior, and individual growth characteristics resulting from DE exposure of dams. Weyand et al (1994) reported that PAH metabolites affect body weight gains. We observed decreases in body weight in young of dams exposed to DE at the highest concentration.…”

00/02209 Tumors and DNA adducts in mice exposed to benzo[a]pyrene and coal tars: implications for risk assessment

“…The risk posed to human health by these tars is determined through the This paper is based on a presentation at the Conference on Current Issues on Chemical Mixtures held [11][12][13] August 1997 in Fort Collins, Colorado. Manuscript received at EHP 17 …”