The training program in cellular and molecular mechanisms of toxicity involves 26 trainers from the Molecular and Environmental Toxicology Center (METC), which also provides central administration. Participating faculty have outstanding training records and well-funded programs, covering a variety of research areas such as developmental toxicology, carcinogenesis, targetorgan toxicity and the roles of inflammation and immunosuppression in disease susceptibility. Graduate students in trainers'labs from METC and other Ph.D. graduate programs (M.D./Ph.D., Cancer Biology, Cellular and Molecular Pathology, Molecular and Cellular Pharmacology, Biomolecular Chemistry, and Pharmaceutical Sciences) will be considered for support for a period of two to three years. Postdoctoral trainees will be supported for two years, but will be required to submit an Individual NRSA application in the first six months. The selection of trainees and oversight of the grant will be carried out by the Program Director and a seven-member Training Grant Committee selected from the 26 trainers for three-year terms. . The Center and training program were reviewed in 2003 by an External Advisory Board, and will be reviewed again by a Board composed of nationally recognized toxicologists at the midpoint of the next funding cycle. This proposal seeks support for eight predoctoral and four postdoctoral positions. All predoctoral trainees take a 12-credit Training Grant core curriculum comprised of courses in basic mechanistic toxicology, the environment and human disease, research ethics and career development, and toxicology research seminar, in addition to courses required by their graduate programs. Pre- and postdoctoral trainees will also be mentored in grant writing and supervision of undergraduate students working in the trainers'labs. A preliminary examination qualifies predoctoral trainees for the final research phase and thesis examination, although laboratory research is continuous from the first semester. Predoctoral trainee progress is monitored by Research Advisory Committees for each trainee (five faculty mentors including at least three trainers) and by the Training Grant Committee. Postdoctoral training is facilitated by appointment of a Postdoctoral Career Advisory Committee (two faculty mentors in addition to a trainer) that will recommend selected didactic courses and collaborations. The recruitment of minorities to the Program is given high priority and is facilitated by a NIEHS-funded Summer Minority Research Program for undergraduates. The University provides two-year special fellowships for minority and disadvantaged students. Upon completion of the training program, graduates usually undertake a period of postdoctoral training, after which they are well qualified to assume responsible career positions in toxicology in academic, governmental, or other public or private research institutions, or industrial laboratories. BACKGROUND This is a competing continuation application for years 31 - 35 of support that requests 8 pre-doctoral students and 4 postdoctoral fellows. During the last funding period, the number of mentors has increased from 19 to 26 with the number of physician-scientist increasing from one to four and the number of veterinarian-scientists increasing from two to three. The focus of the research of the training faculty is in the areas of carcinogenesis, teratogenesis, target-organ toxicity and the roles of environmental exposures on the development of toxicity and/or disease. During the last funding period, the administrative infrastructure was moved so that it is now administered out of the School of Medicine and Public Health instead of the College of Agriculture and Life Sciences. In order to improve the quality of the candidate pool for traineeships, students from other graduate programs will be considered for support as long as they are working in the laboratories of one of the training faculty and are working on a project that is in accordance with the research focus outline by this application.