The goal of this project is to identify and evaluate factors that may influence tumor incidence in laboratory rodents. We continued to investigate the impact of body weight differences on tumor incidence. We found that food restricting dosed and control animals to achieve idealized body weights in both groups may produce false positive outcomes if substantially more food restriction is required for control groups than for dosed animals. We also found that equal food restriction to dosed and control animals may produce false negative outcomes if the resulting body weights are substantially different in dosed and control groups. We also investigated the association between the severity of chronic progressive nephropathy (CPN) and the incidence of adrenal pheochromocytoma in male F344 rats. In control animals the incidence of pheochromocytoma was consistently higher in those animals with the more severe CPN. However, this correlation was not consistently observed in dosed groups. For example, among 28 NTP studies reporting a chemically-related increased severity of CPN, only three had a significant increase in pheochromocytoma. On the other hand, 5/6 NTP studies with increased incidence of pheochromocytoma had some degree of increased CPN severity. We concluded that this association may be a factor in the interpretation of some NTP studies. - Variability; tumor incidence; rodent carcinogenicity bioassays; body weight; dietary restriction. nephropathy, adrenal pheochromocytoma

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES045003-03
Application #
6289959
Study Section
Special Emphasis Panel (BB)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1999
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
Ferguson, Sherry A; Law, Charles Delbert; Kissling, Grace E (2014) Developmental treatment with ethinyl estradiol, but not bisphenol A, causes alterations in sexually dimorphic behaviors in male and female Sprague Dawley rats. Toxicol Sci 140:374-92
Thigpen, Julius E; Setchell, Kenneth D R; Padilla-Banks, Elizabeth et al. (2007) Variations in phytoestrogen content between different mill dates of the same diet produces significant differences in the time of vaginal opening in CD-1 mice and F344 rats but not in CD Sprague-Dawley rats. Environ Health Perspect 115:1717-26
Kissling, Grace E; Dertinger, Stephen D; Hayashi, Makoto et al. (2007) Sensitivity of the erythrocyte micronucleus assay: dependence on number of cells scored and inter-animal variability. Mutat Res 634:235-40
Ghanayem, B I; Witt, K L; El-Hadri, L et al. (2005) Comparison of germ cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect. Biol Reprod 72:157-63
Nwosu, Veronica C; Kissling, Grace E; Trempus, Carol S et al. (2004) Exposure of Tg.AC transgenic mice to benzene suppresses hematopoietic progenitor cells and alters gene expression in critical signaling pathways. Toxicol Appl Pharmacol 196:37-46
Kanno, Jun; Onyon, Lesley; Peddada, Shyamal et al. (2003) The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies. Environ Health Perspect 111:1530-49
Kanno, Jun; Onyon, Lesley; Peddada, Shyamal et al. (2003) The OECD program to validate the rat uterotrophic bioassay. Phase 2: coded single-dose studies. Environ Health Perspect 111:1550-8
Ozaki, Keisuke; Haseman, Joseph K; Hailey, James R et al. (2002) Association of adrenal pheochromocytoma and lung pathology in inhalation studies with particulate compounds in the male F344 rat--the National Toxicology Program experience. Toxicol Pathol 30:263-70
Eastin, W C; Mennear, J H; Tennant, R W et al. (2001) Tg.AC genetically altered mouse: assay working group overview of available data. Toxicol Pathol 29 Suppl:60-80

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