Opinion ID: 510618
Heading Depth: 3
Heading Rank: 3

Heading: Magnitude of the effects in adult rats

Text: 27 Petitioners argue that, even conceding that the data from the CCMA study are relevant to whether two percent is the MTD in rats for Blue No. 2, the data do not show the degree of effect on parameters that would indicate the MTD was achieved. With respect to liver, spleen, and blood glucose observations, petitioners first argue that the differences supposedly observed between control groups and groups treated for various periods with the highest dose of Blue No. 2 are illusory. In making their elaborate and highly technical argument, petitioners rely on non-statistical comparisons of organ and glucose measurements on particular animals. Petitioners' contentions are directly contradicted by the evidence on the record, which incontrovertibly shows statistically significant differences in these parameters between groups of control animals and some groups of animals at the highest dose after various periods of exposure. As the government explains in its brief, statistical significance cannot be discerned by the comparison that petitioners make among individual animals, but only by a comparison of averages according to accepted statistical methods. We must defer to the FDA's explication of the proper method for evaluating statistical significance, which, in any event, accords with well-known principles of statistical analysis. 28 Petitioners also point to the fact that only some groups of animals fed the highest dose of dye showed the organ effects, that the effects appeared only after several months, and that some of the effects were equivocal. We are aware of no evidence on the record that objectively buttresses these claims that the data are inadequate. Petitioners presented no authority for a rigid requirement that differences be shown in all groups of animals after the shortest period of exposure. At least one FDA expert testified otherwise. Hence, the FDA was entitled to conclude that the magnitude and pattern of the effects reported were sufficient to indicate the MTD. 29 Moreover, it is clear from the record that it is impossible to measure precisely the dosage level at which a color additive begins to exert a toxic effect. The OSTP Report, in both draft and final versions, states that the current methodology does not permit determination of the MTD with exactitude. See 49 Fed.Reg. at 21,633; 50 Fed.Reg. at 10,413. The NTP Report repeats the observation that the MTD is an approximation. See Draft Report, Ad Hoc Panel on Chemical Carcinogenesis Testing and Evaluation of the National Toxicology Program, Board of Scientific Counselors 180 (Feb. 15, 1984), J.A. at 167. Thus, the record does not require us to conclude that more clear-cut data are necessary to determine the MTD. We therefore defer to the FDA's decision to rely on the organ weight and glucose data.