Speculations on the rodent carcinogenicity of 30 chemicals currently under evaluation in rat and mouse bioassays organised by the U.S. National Toxicology Program

Abstract

As a contribution to the second round of rodent carcinogenesis prediction organised by the U.S. National Institute of Environmental Health Sciences (NIEHS), speculative predictions for 30 chemicals currently under evaluation in U.S. National Toxicology Program (NTP) rodent bioassays are presented. Core chemical data received from NIEHS were supplemented by relevant information from commercially available scientific databases to provide input for reasoned assessment. For each chemical, carcinogenesis by a genotoxic or nongenotoxic mechanism or noncarcinogenesis is predicted; species-and target organ-specific predictions are also presented, together with arbitrary indices of confidence in each such prediction. In all or nearly all cases, an element of informed speculation was a necessary part of the prediction process, but the rationale for each decision is briefly described. It is predicted that ten chemicals will prove noncarcinogenic, five will be carcinogenic to mice only, and 15 will induce tumours in both species.

Oxymetholone: III. Evaluation in the p53+/- Transgenic Mouse Model

“…The results of these studies, along with the lack of mutagenicity (4), indicate that oxymetholone exerted its carcinogenic action in Tg.AC mice through a tumor-promoter mechanism rather than a tumor-initiator mechanism. This conclusion is consistent with the known hormonal characteristics of oxymetholone and its positive response predicted by Bootman (1) in a National Toxicology Program (NTP) 2-yr rat bioassay (9). The present study was initiated and completed prior to public disclosure of the results from the NTP bioassay.…”

Oxymetholone: II. Evaluation in the Tg.AC Transgenic Mouse Model for Detection of Carcinogens

“…The incidence by week of papillomas is shown in Fig. 3. Although less striking in magnitude, skin tumor multiplicity (expressed as either number of tumors per affected animal or number of tumors per dosed animal) was also increased by repeated applications of oxymetholone.…”

“…The NTP rat bioassay and evaluation were conducted concurrently with the present study. Bootman (3) predicted that oxymetholone would exhibit hepatocarcinogenic activity in that assay.…”

Gallium

“…9 1996). Gallium arsenide dissociation leads to arsenic release in vivo, and arsenic can be mutagenic and carcinogenic; thus, the arsenic moiety of GaAs may be responsible for any mutagenic or carcinogenic activity (Bootman 1996). Gallium arsenide was not mutagenic in several strains of Salmonella, in either the presence or absence of metabolic activation enzymes (NTP 2000).…”