As part of the National Toxicology Program one of our mandates is to determine the reproductive toxicity of industrial and environmental chemicals/agents/conditions in order to protect the public from reproductive health hazards. In order to accomplish this goal we have devised a test for reproductive toxicity called Reproductive Assessment by Continuous Breeding (RACB). It is similar enough to conventional multigeneration studies to be useful to regulatory agencies but also has additional endpoints which will identify a toxicant which does not specifically alter fertility. It also provides an indication of the site of action to aid in the design of follow-up experiments on the site and mechanism of action of toxicants. This RACB protocol improved over the conventional fertility tests by dosing breeding pairs over 98 days (mice) which resulted in up to five litters being produced thereby significantly increasing the sensitivity of the test. In addition, it contains histological assessment of the testis and epididymis, measurement of epididymal sperm number, motility and morphology, and weight of the testis, epididymis, seminal vesicles, and prostate in order to assess any change in spermatogenesis. A crossover mating trial is used to determine the sex affected. An assessment of the second generation with a complete necropsy including histology, sperm assessment and reproductive organ weights also improves the sensitivity of the test. This RACB protocol will be used in this contract to identify chemicals/agents/conditions of environmental and industrial origin which are reproductive toxicants. This information will then be used by government regulatory agencies to aid in their decision making process and by the NTP as a starting point for continued studies on the site and mechanism of action of these toxicants.
