Oncogenicity study of trifluralin in B6C3F1 mice.
B6C3F1 mice were maintained for 24 months on diets containing 0, 563, 2250 or 4500 ppm trifluralin. These dietary concentrations corresponded to daily doses of approximately 70, 285 or 570 mg/kg body weight, respectively. The control group contained 120 mice/sex and treated groups consisted of 80 mice/sex. There were no treatment-related effects on the survival, appearance or behaviour of the mice. Survival at test termination was at least 67% in each group. Compared with controls, mean body weight was significantly reduced in a dose-related manner in mice of both sexes given the 2250 and 4500 ppm diets. At 21 months, the reduction in body weight was greater than or equal to 15 and greater than or equal to 30%, respectively. At study termination, dose-related decreases in erythrocytic and leucocytic values were also observed at dietary levels of 2250 and 4500 ppm. In clinical chemistry evaluations, blood urea nitrogen levels and alkaline phosphatase activity in mice of both sexes were significantly increased at trifluralin levels of 2250 and 4500 ppm. Blood urea nitrogen also showed a marginal increase in females given the low dose of trifluralin. Alanine aminotransferase activity was significantly increased in males at all treatment levels. Although there were a number of absolute and relative organ weight changes in all three treatment groups that were significantly different from the control values, the reduced relative kidney weights in males and the increased relative liver weights in both sexes at dietary levels of 2250 and 4500 ppm were the only changes that could be correlated with altered clinical chemistry values.(ABSTRACT TRUNCATED AT 250 WORDS)
Francis
P C
PC
Toxicology Research Laboratories, Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, IN 46140.
Emmerson
J L
JL
Adams
E R
ER
Owen
N V
NV
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced* / Q000473:pathology; D009602:Nitrosamines / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D012737:Sex Factors; D014274:Trifluralin / Q000008:administration & dosage / Q000592:standards / Q000633:toxicity*
D002273:Carcinogens; D009602:Nitrosamines; D014274:Trifluralin