Weyand E H, Wu Y, Patel S, Goldstein L
College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855-0789.
J Toxicol Environ Health. 1994 May;42(1):89-107. doi: 10.1080/15287399409531865.
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.
评估了饮食中添加人造煤气厂残渣（MGP）对雄性和雌性B6C3F1小鼠的潜在毒性。此外，还通过监测尿液中的多环芳烃（PAH）代谢物以及前胃和肺组织中的DNA加合物形成情况，研究了MGP化学成分的生物利用度。将含有0.05%、0.25%、0.50% MGP或0.005%苯并[a]芘（BaP）的基础凝胶饲料喂养动物94天和185天。小鼠很容易食用掺假饲料，没有任何急性毒性的迹象。小鼠摄入的MGP和BaP总量分别为118至2604毫克和12至29毫克。喂食对照或BaP饲料的雄性小鼠以及喂食0.05% MGP饲料的雌性小鼠体重增加最多。喂食0.50% MGP饲料的雄性和雌性小鼠体重增加最少。通过监测喂食0.25% MGP饲料的雄性小鼠尿液中PAH代谢物的排泄情况，评估了MGP化学成分的生物利用度。通过高效液相色谱分析确定，1-羟基芘是在整个185天的饲料投喂期间小鼠排泄的主要荧光代谢物。尸检时，未检测到与化学物质相关的肉眼可见病变。此外，在喂食0.50% MGP或BaP掺假饲料的动物所取组织中，也未发现与处理相关的微观病变。采用32P后标记分析法评估MGP和BaP诱导的肺和前胃组织中的DNA加合物形成情况。由MGP化学成分形成的DNA加合物水平与动物摄入的物质数量平行。当小鼠摄入0.25%或0.50% MGP饲料时，肺中的DNA加合物水平明显高于前胃中的水平。这些研究表明，连续185天摄入MGP或BaP，在剂量高达0.50% MGP或0.005% BaP时，不会导致急性毒性或与化学物质相关的病变。
