In addition to publishing updated tumor rates in control Fischer 344 rats and B6C3F1 mice, we compared the results of a number of chemicals evaluated both in NTP rodent carcinogenicity studies and in genetically altered mice. Preliminary results indicated that genetically altered mice have the potential to serve as more rapid and less expensive test systems to identify carcinogens. Twelve chemicals in the NTP database were identified that produced nasal cavity tumors. We found that most of the nasal carcinogens (1) produced tumor increases in both sexes, (2) produced tumors at other sites as well, (3) had significantly reduced survival at doses that were carcinogenic, and (4) were genotoxic. Finally, we found a striking inverse correlation between the incidences of pituitary gland tumors and testis adenoma in control male F344 rats. In dermal and inhalation studies, the control group incidences of both tumor types average approximately 65%. In contrast, in feeding and gavage studies, control groups consistently have lower incidences of pituitary gland neoplasms (averaging 32%), and higher incidences of testis tumors (averaging nearly 90%). One hypothesis that could account for this inverse correlation is stress associated with individual housing, a protocol that is used in dermal and inhalation studies, but not in feeding and gavage studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES045004-02
Application #
6106656
Study Section
Special Emphasis Panel (BB)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Kissling, Grace E; Haseman, Joseph K; Zeiger, Errol (2015) Proper interpretation of chronic toxicity studies and their statistics: A critique of ""Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example"". Toxicol Lett 237:161-4
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Auerbach, Scott S; Shah, Ruchir R; Mav, Deepak et al. (2010) Predicting the hepatocarcinogenic potential of alkenylbenzene flavoring agents using toxicogenomics and machine learning. Toxicol Appl Pharmacol 243:300-14
Cunningham, Michael L; Collins, Bradley J; Hejtmancik, Milton R et al. (2010) Effects of the PPAR? Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism. PPAR Res 2010:
Singh, B P; Nyska, A; Kissling, G E et al. (2010) Urethral carcinoma and hyperplasia in male and female B6C3F1 mice treated with 3,3',4,4'-tetrachloroazobenzene (TCAB). Toxicol Pathol 38:372-81
Stout, Matthew D; Herbert, Ronald A; Kissling, Grace E et al. (2009) Hexavalent chromium is carcinogenic to F344/N rats and B6C3F1 mice after chronic oral exposure. Environ Health Perspect 117:716-22
Knudsen, G A; Cheng, Y; Kuester, R K et al. (2009) Effects of dose and route on the disposition and kinetics of 1-butyl-1-methylpyrrolidinium chloride in male F-344 rats. Drug Metab Dispos 37:2171-7
Cheng, Y; Wright, S H; Hooth, M J et al. (2009) Characterization of the disposition and toxicokinetics of N-butylpyridinium chloride in male F-344 rats and female B6C3F1 mice and its transport by organic cation transporter 2. Drug Metab Dispos 37:909-16

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