Oil gavage test-compound administration effects in NTP carcinogenesis-toxicity testing.
Consulting toxicologists began in 1982 to question the use and potential involvement of oil gavage test-compound administration in unexpected NTP carcinogenesis responses. Investigations have focused on corn oil gavage alternatives, vehicle type and volume, alteration of MTD, teratogenic effects, disposition of test compounds, and target tissues. Micoencapsulation will require considerable development research to make it a suitable alternative. Vehicle type and volume appear to have different effects on the apparent MTD, teratogenicity and disposition of very similar compounds. Only two tissue effects have been observed in the NTP oil gavage bioassay data. First, there is a sporadic and weak association with exocrine pancreatic acinar cell proliferative lesions; these lesions are highly correlated with overweight male Fischer 344/N rats. Second, leukemia is reduced about 50 percent in the male Fischer 344/N rats; this is a strong association which results in an 8-10 percent increase in survival. The protective effect of corn oil gavage is remarkable and there is no significant enhancement of tumor development. Corn oil gavage under the conditions of the NTP carcinogenesis bioassay does contribute to overnutrition and undesirable increased body weight, especially in male Fischer 344/N rats. The NTP and NCTR research programs include research plans to address critical oil gavage, diet composition feeding regimen, exercise and hormonal status questions. Results of these studies will point the way to improving long-term carcinogenesis and toxicity testing.
D000818:Animals; D001681:Biological Assay; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002725:Chloroform / Q000633:toxicity; D004750:Enteral Nutrition; D007928:Lethal Dose 50; D008722:Methods; D009152:Mutagenicity Tests; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009821:Oils
D009821:Oils; D002725:Chloroform; D002251:Carbon Tetrachloride