Dose and time relationships for tumor induction in the liver and esophagus of 4080 inbred rats by chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine.

摘要: A Weibull analysis is presented of the dose and time relationships for effects on 4080 inbred rats chronic ingestion in drinking water 16 different doses N-nitrosodimethylamine (NDMA) or N-nitrosodiethylamine (NDEA). The sites chiefly affected were liver (by both agents) esophagus NDEA only). Since experiment continued into extreme old age, became measurable at only 0.01 to 0.02 mg/kg/day, which an order magnitude lower than previously achieved. (After 2 years treatment, however, TD50 needed halve proportion tumorless survivors would have been about 0.06 mg/kg/day NDEA, 0.12 NDMA.) general pattern response was that natural logarithm probability remaining given by product two terms, first (the "Weibull b value") depending rate but not duration exposure second all duration. For types tumor dependence fairly similar (and each term taken be -t7, where t = treatment), quite different. esophageal tumors, value" approximately proportional cube (males 21 d3, females 11 d mg/kg adult body weight/day), background incidence unmeasurably low. tumors induced value fourth power + 0.04 [males, 19 (d 0.04)4; females, 32 0.04)4], although somewhat cell tumor. This one formula implies approximate linearity low cubic relationship within higher range studied. NDMA, sixth 0.1 37 0.1)6; 51 0.1)6], again with some variation between types, implying doses. These algebraic formulae should, course, trusted they derived, particularly above it.(ABSTRACT TRUNCATED AT 400 WORDS)