The preceding paper described our numerical index of carcinogenic potency, the TD54, and the statistical procedures adopted for estimating it from experimental data. This paper presents the Carcinogenic Potency Database, which includes results of about 3000 long-term, chronic experiments of 770 test compounds. Part II is a discussion of the sources of our data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Part III is a guide to the plot of results presented in Part IV. A number of appendices are provided to facilitate use of the database. The plot includes information about chronic cancer tests in mammals, such as dose and other aspects of experimental protocol, histopathology and tumor incidence, TD5o and its statistical significance, dose response, author's opinion and literature reference. The plot readily permits comparisons of carcinogenic potency and many other aspects of cancer tests; it also provides quantitative information about negative tests. The range of carcinogenic potency is over 10 million-fold. Part 1: IntroductionThis paper presents the Carcinogenic Potency Database, which includes data on approximately 3000 longterm, chronic animal experiments with about 770 chemicals. The preceding paper (1) described our numerical index of carcinogenic potency, the TD50, and the statistical procedures adopted for estimating it from experimental data. weight/day) which, if administered chronically for the standard lifespan of the species, will halve the probability of remaining tumorless throughout that period. A TD50 can be computed for any particular type of neoplasm, for any particular tissue, or for any combination of these.Part II of this paper discusses the sources of bioassay results and the rationale for including particular experiments and particular target sites in the database. The conventions adopted in summarizing and standardizing the literature are also described. In Part IV we present a plot of the database. In

Values of klsO/k18,, have been measured for several reactions of methyl formate-methoxyl-l8O. The ratios for acid-catalyzed hydrolysis, alkaline hydrolysis, and general base catalyzed hydrolysis in succinate buffer are 1.0009 + 0.0004, 1.0091 + 0.0002, and 1.0115 i . 0.0002, respectively. The maximum expected effect, 1.052, for ratedetermining scission of the acyl carbon-methoxyl oxygen bond was calculated from the observed difference in the stretching frequencies between l60 and l*O ester. The observed isotope effect for hydrazinolysis under conditions of rate-determining breakdown of the tetrahedral intermediate at low pH is 1.0621 =t 0.0008, while at high pH, where attack of hydrazine on the ester or a proton transport step is rate determining, it is only 1.0048 i . 0.0006. The values of the ratios of the rates of hydrolysis to carbonyl oxygen exchange for methyl formate are 11.4 f 0.1 in acid and 18.3 f 0.4 in alkaline solution. The extremely small kinetic isotope effect observed for acid-catalyzed hydrolysis suggests a mechanism in which equilibrium protonation of the ester is counterbalanced by the normal kinetic isotope effect for the attack of water on the oxocarbonium ion. The small but significant isotope effects observed for alkaline hydrolysis, general base catalyzed hydrolysis, and hydrazinolysis at high pH suggest a transition state in which the order of the acyl carbon-methoxyl oxygen bond of 1.1 5 in the ester is only slightly reduced in the transition state. xtreme transition-state geometries for acyl transfer E reactions of esters are represented by that reached very early along the reaction coordinate in alkaline hydrolysis, perhaps en route to a tetrahedral intermediate (I), and by the late transition state in which the breakdown of a tetrahedral intermediate is rate determining (II).2 The transition states for other simple 6-0

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The reaction of butyraldoxime with nitrous acid without excess mineral acid must follow, in part, a different pathway because the major off-gas is NO (67%). As in the excess mineral acid catalyzed reaction, both the N2 and N20 show a 50% enrichment in 1 . Thus these gases come equally from nitrous acid and oxime. The fact that so much NO is produced and that it all comes from the nitrous acid forms the basis for our considerations in this case. It should be emphasized that this NO does indeed come from a reaction of nitrous acid with the oxime. Under the same conditions of solvents, concentration, and temperature, nitrous acid does not react in a self-decomposition to give NO as an off-gas. Only when the oxime is added is NO produced. ime, 557-30-2. Acknowledgment.-We should like to thank Dr. . P. Doyle for his help in formulating some of the mechanisms described herein.A Simple High Yield Synthesis of Methanol-18#) and Ethanol-18#)1

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