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 a mouse study of the role of genetic diversity in responding to ionizing radiation. Known as the "Diversity Outcross", eight strains of mice were interbred to generate genetic heterogeneity approximating the degree of heterogeneity seen in humans. Mice were exposed to ionizing radiation (or control) then assessed for formation of micronucleated cells in blood and bone marrow;micronucleated cells are indicators of chromosome damage. Preliminary data show that there is a wide range of responses to radiation among the strains. We have identified two areas, located within chromosome 2 and chromosome 10, that may explain differences in susceptibility. The NTP often collects a large number of tissue samples in a single study and it may not be feasible to immediately assay all samples;samples may need to be stored for later analysis. To ensure that the data collected from stored tissue samples remains of high quality, we collaborated on the design and statistical analysis of several studies to examine the stability of hematology, clinical chemistry and genetic toxicity measurements made on tissues having differing storage conditions, i.e., length of time stored and storage temperature. So far, we have established that comet assay results remain stable when tissue is frozen for up to 8 weeks.

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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
Thigpen, Julius E; Setchell, Kenneth D R; Kissling, Grace E et al. (2013) The estrogenic content of rodent diets, bedding, cages, and water bottles and its effect on bisphenol a studies. J Am Assoc Lab Anim Sci 52:130-41
Boyd, Windy A; Smith, Marjolein V; Kissling, Grace E et al. (2010) Medium- and high-throughput screening of neurotoxicants using C. elegans. Neurotoxicol Teratol 32:68-73
Stout, Matthew D; Kissling, Grace E; Suarez, Fernando A et al. (2008) Influence of Helicobacter hepaticus infection on the chronic toxicity and carcinogenicity of triethanolamine in B6C3F1 mice. Toxicol Pathol 36:783-94
Kissling, Grace E; Portier, Christopher J; Huff, James (2008) MtBE and cancer in animals: statistical issues with poly-3 survival adjustments for lifetime studies. Regul Toxicol Pharmacol 50:428-9
Hard, Gordon C; Seely, John Curtis; Kissling, Grace E et al. (2008) Spontaneous occurrence of a distinctive renal tubule tumor phenotype in rat carcinogenicity studies conducted by the national toxicology program. Toxicol Pathol 36:388-96