Chronic toxicity studies can require that animal subjects be exposed to varying doses of test agents over an extended period of time. There is an increase in the incidence of health problems over time, due to both aging and the toxicity of the test agent, raising concerns about the welfare of the animals. At the HSUS workshop, Dr. Fentener van Vlissingen addressed these health and welfare implications by presenting a retrospective evaluation of a chronic study, and the potential use of clinical signs for the determination of humane endpoints. In addition, she emphasized that the determination of criteria for humane endpoints, with the goal of minimization of discomfort, should be harmonized internationally.
Fentener van Vlissingen assessed various factors in the 507 rats used in chronic studies, including clinical signs (both specific and non-specific), body weight, development of masses and postmortem pathology. "Related discomfort" was determined retrospectively, based on both clinical and pathological observations. It was concluded that humane endpoints should include both specific and non-specific (e.g., poor general appearance) clinical signs. For example, a significant decrease or increase in body weight was found in those animals categorized as exhibiting "serious discomfort." It was also found that many of the animals categorized as exhibiting "serious discomfort" had only non-specific clinical signs.
To view the full text of Fentener van Vlissingen's paper, "Retrospective evaluation of clinical signs, pathology, and related discomfort in chronic studies," download the PDF.
 | Get Adobe Acrobat Reader |
