We contributed to NTP Technical Reports on two-year rodent carcinogenicity studies of beta-myrcene, 3,3',4,4'-tetrachloroazobenzene, 2,3',4,4',5-pentachlorobiphenyl (PCB 118), androstenedione, tetralin and goldenseal root powder. These reports were reviewed and approved by the NTP Technical Reports Subcommittee in February, 2009. We contributed to several smaller studies focused on the effects of methylphenidate (Ritalin). These studies included examination of genetic damage in the heart and brain of rats, as well as genetic damage in blood cells of children prescribed the drug. We found no evidence of genetic damage in either the rats or the children. An important approach to evaluating and interpreting NTP data is to make comparisons across multiple studies. This year, we continued two such investigations. 1) We described the occurrence of lung tumors in NTP's long-term rodent studies. 2) We characterized a spontaneous kidney tumor in rats. Lung tumors are one of the most common tumors in NTP mouse studies, so understanding how they vary across different factors in control animals, such as route of exposure, diet, and housing density, is crucial to interpreting the effects of environmental exposures on lung tumors. In our second study, we describe the morphology and prevalence of a kidney tumor that apparently occurs spontaneously in rats. Currently, the NTP does not distinguish this tumor from chemically-induced kidney tumors;however, separating the spontaneous tumor from the chemically-induced tumors should improve the NTP's ability to detect chemical effects on the kidney. The NTP is interested in reducing, replacing and refining the use of rodents in laboratory studies. We continued to provide advice on experimental design and statistical methods for evaluating alternative methods for NTP's toxicity and carcinogenicity testing. These include: 1) evaluating electrocardiogram data from a dog model for testing whether drugs prolong the QT wave in the heart beat which may ultimately lead to lethal arrhythmias, and 2) continuing our evaluation of the usefulness of growth, reproduction, feeding, and movement of C. elegans for assessing toxicity. We are also involved in 3) analyzing high throughput data from cell-based assays of chemicals selected by the NTP, that were generated by the NIH Chemical Genomics Center.
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