Rodent bedding, diet, and drinking water may contain compounds that affect the same endpoints that are the target of NTP's testing program, such as reproduction and development. For example, endotoxins (a byproduct of mold) can mask responses to exposure to asthma-causing agents. Likewise, phytoestrogens in the rodent diet can mask responses to exposure to estrogenic compounds. We are working with the NIEHS Quality Assurance Laboratory to quantify these effects and develop guidelines for limits on contaminants in bedding, diet and drinking water of rodent studies. We contributed to the study design of a multi-strain mouse study in which different strains are exposed to ionizing radiation then followed up for development of tumors. These strains were selected to represent a broad range of genetic variation. Although the data are not yet complete, the early indications are that different strains have a range of susceptibility to radiation and show varying locations and rates of tumors. Some compounds cause kidney tumors in rats exposed for two years. Two-year studies, however, are expensive and time-consuming. We have identified early onset kidney lesions that may predict later kidney tumors in rats. By evaluating data from a number of previous NTP studies, we confirmed the association between early onset lesions and kidney tumors, and showed that the association is not affected by type of diet or route of compound exposure. This finding suggests that short-term, less expensive studies may be useful in identifying kidney carcinogens.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2011
Total Cost
$83,667
Indirect Cost
City
State
Country
Zip Code
Stanko, Jason P; Kissling, Grace E; Chappell, Vesna A et al. (2016) Differences in the Rate of in Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure. Toxicol Pathol 44:1021-33
Churchill, Sheba R; Morgan, Daniel L; Kissling, Grace E et al. (2016) Impact of Environmental Enrichment Devices on NTP In Vivo Studies. Toxicol Pathol 44:233-45
French, John E; Gatti, Daniel M; Morgan, Daniel L et al. (2015) Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity. Environ Health Perspect 123:237-45
Filgo, Adam J; Quist, Erin M; Hoenerhoff, Mark J et al. (2015) Perfluorooctanoic Acid (PFOA)-induced Liver Lesions in Two Strains of Mice Following Developmental Exposures: PPAR? Is Not Required. Toxicol Pathol 43:558-68
Quist, Erin M; Filgo, Adam J; Cummings, Connie A et al. (2015) Hepatic Mitochondrial Alteration in CD-1 Mice Associated with Prenatal Exposures to Low Doses of Perfluorooctanoic Acid (PFOA). Toxicol Pathol 43:546-57
Ramot, Yuval; Kodavanti, Urmila P; Kissling, Grace E et al. (2015) Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure. Inhal Toxicol 27 Suppl 1:26-38
Ray, Mitas; Shockley, Keith; Kissling, Grace (2014) Minimizing Systematic Errors in Quantitative High Throughput Screening Data Using Standardization, Background Subtraction, and Non-Parametric Regression. J Exp Second Sci 3:
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
Jayes, Friederike L; Burns, Katherine A; Rodriguez, Karina F et al. (2014) The naturally occurring luteinizing hormone surge is diminished in mice lacking estrogen receptor Beta in the ovary. Biol Reprod 90:24
Cora, Michelle C; Neel, Jennifer A; Grindem, Carol B et al. (2013) Comparison of automated versus manual neutrophil counts for the detection of cellular abnormalities in dogs receiving chemotherapy: 50 cases (May to June 2008). J Am Vet Med Assoc 242:1539-43

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