National Toxicology Program

Table of Contents

Background on Concept Reviews
Rodent Disease Diagnostic Laboratory: Dr. Ghanta N. Rao
Genetic Monitoring of Rodents: Dr. Ghanta N. Rao

BACKGROUND ON CONCEPT REVIEWS

NTP contracts, interagency agreements, and grants support a variety of activities ¿ toxicologic characterization, testing, methods development, and program resources (i.e., chemistry, occupational health and safety, animal production, pathology, quality assurance, archives, etc.).

Prior to issuance of a Request for Proposal (RFP) or a Request for Application (RFA), a project concept review is required. These project concepts in many instances may consist of more than one contract, interagency agreement, or grant. Concept reviews are needed for new projects, recompetitions with changes in statements of work, and projects ongoing for five years or more since the last concept review.

The project concept reviews are conducted by the NTP Board of Scientific Counselors and are open to the public so long as discussions are limited to review of the general project purposes, scopes, goals, and various optional approaches to pursue the overall program objectives. The meeting will be closed to the public, however, if the concept discussions turn to the development or selection of details of the projects or RFPs/RFAs, such as specific technical approaches, protocols, statements of work, data formats, or product specifications. Closing the session is intended to protect the free exchange of the advisory group members¿ opinions and to avoid premature release of details of proposed contract projects or RFPs/RFAs.

The Board members are asked to review the project concepts for overall value and scientific relevance as well as for fulfilling the program goal of protecting public health. Specific areas should include:

1. scientific, technical or program significance of the proposed activity;
2. availability of the technology and other resources necessary to achieve required goals;
3. extent to which there are identified, practical scientific or clinical uses for the anticipated results; and
4. where pertinent, adequacy of the methodology to be used in performing the activity.

CONTRACT TITLE: Rodent Disease Diagnostic Laboratory

PROJECT OFFICER: Ghanta N. Rao, (919) 541-7899

OBJECTIVE: To continue to provide rodent disease diagnostic services to the rodent production colonies and the toxicity and carcinogenicity studies. This Project/Contract is necessary 1) to maintain the microbial quality of animals supplied for the studies, 2) to document the infection and disease status of the animals during the course of the studies, and 3) to implement procedures to control and prevent infections and diseases in the production colonies and the toxicity and carcinogenicity studies.

CONCEPT STATEMENT: Centralized colonies of rodents with homogeneous genetic properties and defined health profiles ensure an adequate and continuous supply of defined quality animals for the toxicity and carcinogenicity studies. It is necessary to perform rodent disease diagnostic procedures to characterize infection and disease status of animals prior to and during the toxicity and carcinogenicity studies. Infection and disease status information is necessary for interpretation of studies and to implement control and preventive measures for future studies.

This contract/project will provide rodent disease diagnostic laboratory services for monitoring the microbial status and health status of the animals and for investigating any disease conditions that might appear. Animals from the production colonies are examined for pathogenic microorganisms and parasites These evaluations include pathologic examination of selected tissues for microbial and parasitic lesions. Serum samples from sentinel animals in the toxicology studies are evaluated for viral antibody profiles. In addition, sentinel animals and tissues from animals on studies are evaluated for microbial or parasitic disease conditions. This program is necessary to ensure the production of disease-and-infection free rodents and to maintain the toxicity and carcinogenicity studies free of infections and diseases.

PROPOSED CHANGES TO THE CURRENT STATEMENT OF WORK: There are no substantial changes to the Statement of Work. However, the Statement of Work is revised to update the pathogenic agents and diagnostic procedures for some agents.

CONTRACT TITLE: Genetic Monitoring of Rodents

PROJECT OFFICER: Ghanta N. Rao, (919) 541-7899

OBJECTIVE: To continue to provide genetic monitoring of inbred stocks at the rodent production centers. This contract is necessary to maintain the genetic integrity of the rodent production colonies as well as the animals supplied for toxicity and carcinogenicity studies.

CONCEPT STATEMENT: This project provides genetic monitoring to assure the genetic integrity of inbred F344/N rats, B6C3F1 hybrid mice and other strains of rodents produced for the NTP studies. Genetic loci are being monitored by electrophoresis of erythrocyte Iysates, kidney homogenates and serum proteins to detect contamination, back-crossing and mutations. The genetic integrity of inbred rodents is also being evaluated by skin grafting to detect genetic drift due to fixed mutations. In addition, kidneys from B6C3F1 hybrid mice received at the study laboratories are being evaluated for biochemical markers by electrophoresis to assure that the mice used for the NTP studies are B6C3F1 hybrid. Constant monitoring for biochemical genetic variants and fixed mutations of foundation and production stock and test animals will ensure that data from NTP animal studies are collected from genetically homogeneous rats and mice.

PROPOSED CHANGES TO THE CURRENT STATEMENT OF WORK: None. However, when procedures are established to monitor a large number of DNA based markers by RFLP, SSLP, etc..., such procedures may be added instead of or in addition to biochemical markers and skin grafting procedure to detect fixed mutations.