On the Relationship Between Carcinogenicity and Acute Toxicity

Abstract

Parodi et al. and Zeise et al. found a surprising statistical correlation (or association) between acute toxicity and carcinogenic potency. In order to shed light on the questions of whether or not it is a causal correlation, and whether or not it is a statistical or tautological artifact, we have compared the correlations for the NCI/NTP data set with those for chemicals not in this set. Carcinogenic potencies were taken from the Gold et al. database. We find a weak correlation with an average value of TD50/LD50 = 0.04 for the non-NCI data set, compared with TD50/LD50 = 0.15 for the NCI data set. We conclude that it is not easy to distinguish types of carcinogens on the basis of whether or not they are acutely toxic.

Assessing Human Health Response in Life Cycle Assessment Using ED10s and DALYs: Part 1—Cancer Effects

“…In the absence of alternatives, some authors (Zeise, Crouch, & Wilson, 1984; Zeise, Wilson, & Crouch, 1986; Metzger, Crouch, & Wilson, 1989; Gold & Zeiger, 1997) suggest the notion that readily available acute lethal measures might be used to provide an initial idea of cancer risk. This proposal is briefly examined here for the ED 10 from a statistical perspective for the 44 chemicals addressed with bioassay data.…”

Limitations to Empirical Extrapolation Studies: The Case of BMD Ratios

“…Indeed, the roots of the problem (measurement error and censoring) are fundamental and likely to have broader implications. They are likely to a®ect most other empirical extrapolation approaches, including`non-linear' analyses of ratios [38], regression studies extending beyond pair-wise comparisons [39,40], and other studies exploring relationships between alternative toxicity estimates [41,42,43,44,45]. They also have implications for studies of optimal design and studies comparing the relative merits of alternative toxicity measures (e.g., BMD versus NOAEL).…”

“…Several papers have debated whether the correlation observed between mouse and rat cancer potency's, is merely an artifact of a coordinated choice of test doses [48,49,50,38,51,52,53].…”

Estimation of Maximum Tolerated Dose for Long‐Term Bioassays from Acute Lethal Dose and Structure by QSAR

“…(') It has recently been suggested,(*-') however, that a significant relationship may, in fact, exist, and possible explanations have been suggested. (2)(3)(4)(5)(6)(7)(8) Two dose which can be administered to he animals without chemicals only rarely increased tumor incidence. (g) Zeise causing an unacceptable number of premature deaths or et and Bernstein er have that the serious adverse effects which would jeopardize the conmaximum dose and potency are evidently related.…”

“…(') It has recently been suggested,(*-') however, that a significant relationship may, in fact, exist, and possible explanations have been suggested. (2)(3)(4)(5)(6)(7)(8) Two findings have become evident in the NCUNTP To insure that there is adequate survival of experimental animals to their nominal lifetime on the one hand, and development of a sufficient number of tumors at acceptable cost on the other, oncogene& studies gen-bioassays: (a) of the tested induced tuerally employ the maximum tolerated dose (m), the in all of the treated and (b) dose which can be administered to he animals without chemicals only rarely increased tumor incidence. (g) Zeise causing an unacceptable number of premature deaths or et and Bernstein er have that the serious adverse effects which would jeopardize the con-maximum dose and potency are evidently related.…”