Research on the Radiotoxicology of Plutonium Using Animals: Consideration of the 3Rs-Replace, Reduce, Refine.

To characterize the health effects of incorporated plutonium, many experiments have been conducted using different animal models. These range from (1) applied (tissue uptake/retention determination, decorporation therapy efficacy), (2) fundamental (gene expression, cancer induction), and (3) dosimetry models. In recent years, the use of animals for scientific purposes has become a public concern. The application of the 3Rs - Replace (use of alternative methods or animals not considered capable of experiencing pain, suffering, and distress), Reduce (reduction in animal numbers), and Refine (better animal welfare and minimization of suffering, pain and distress) - has increased to address ethical concerns and legislative requirements. The introduction of novel non-animal technologies is also an important factor as complementary options to animal experimentation. In radiotoxicology research, it seems there is a natural tendency to Replace given the possibility of data reuse obtained from contamination cases in man and animal studies. The creation of "registries" and "repositories" for nuclear industry workers (civil and military) is now a rich legacy for radiotoxicological measurements. Similarly, Reduction in animal numbers can be achieved by good experimental planning with prior statistical analyses of animal numbers required to obtain robust data. Multiple measurements in the same animal over time (external body counting, excreta collection) with appropriate detection instruments also allow Reduction. In terms of Refinement, this has become "de rigueur" and a necessity given the societal and legal concerns for animal welfare. For research in radiotoxicology, particularly long-term studies, better housing conditions within the constraints of radiation protection issues for research workers are an important concern. These are all pertinent considerations for the 3Rs remit and future research in radiotoxicology.