NTP Database Summarization And Evaluation

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

We contributed to NTP Technical Reports on two-year rodent carcinogenicity studies of 5-(hydroxymethyl)-2-furfural, 1,2-dibromo-2,4-dicyanobutane, chromium picolinate monohydrate, isoeugenol, dibromoactonitrile and bromochloroacetic acid. We also contributed to an NTP Toxicity report on short-term rodent studies of estragole. These reports were reviewed and approved by the NTP Technical Reports Subcommittee in February, 2008. [unreadable] [unreadable] We contributed to several smaller studies focused on heart damage resulting from exposure to cardiac toxins, such as AZT, 3TC, ephedrine, caffeine, ma huang, and bis(2-chloroethoxy) methane. We identified several early indicators of heart damage that will prove useful in future studies. Furthermore, we provided the first evidence of a dose-response relationship between ephedrine and heart damage in rodents. The response was exacerbated by concomitant exposure to caffeine. We observed a similar response when ma huang, a 'natural' form of ephedrine, was used in conjunction with caffeine. This information is useful to regulatory agencies because some diet pills contain ephedrine or ma huang and caffeine.[unreadable] [unreadable] An important approach to evaluating and interpreting NTP data is to make comparisons across multiple studies. This year, we undertook two such investigations. 1) We contributed to a summary and characterization of the chemical-induced lung tumors found within the 545 NTP peer-reviewed two-year rodent studies. 2) We investigated the association, in NTP rats, between kidney lesions in short-term studies and chemical-induced kidney tumors in long-term studies.[unreadable] [unreadable] The NTP is interested in reducing, replacing and refining the use of rodents in laboratory studies. We provided advice to the NTP on experimental design and statistical methods for evaluating alternative methods for 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.