In silico evaluation of correlations between clinical signs and pathological findings in toxicity studies with rats
Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
In 2011 approximately 1 million animals were used in toxicity testing within EU. The use of animals is criticized and to minimize both the use and the suffering of research animals there are several laws, regulations and guidelines to consider. Even if all of them take the 3Rs (Replacement, Reduction and Refinement) into consideration, there are always improvements that can be made as new scientific practices and knowledge develops. Clinical observations and body weight loss are indicators of severe pain, distress or suffering, as well as signs of general toxicity, and are used in toxicity studies in combination with toxicokinetics, blood parameters, immune cells and pathological findings to assess the safety of a drug candidate. The aim of the present study was to study possible correlations between clinical signs and pathological findings. Data from two in vivo studies with rats was compiled and analyzed with the multivariate analysis method Partial Least Squares regression. The results showed that there were correlations between some clinical signs of toxicity and pathological findings in thymus, bone marrow, intestines and liver. In addition in vitro results from human immune cell function analysis correlated well with the in vivo results as well as with pathological findings in the thymus. The conclusion is that correlations between some clinical signs and pathological findings might be used as early markers in toxicity studies, which would develop the study design of toxicity studies that embrace the 3Rs.
Place, publisher, year, edition, pages
2016. , 48 p.
3Rs, Toxicity studies, Clinical signs, Pathological findings
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-274396OAI: oai:DiVA.org:uu-274396DiVA: diva2:896415
Subject / course
Master of Science Programme in Pharmacy
Hellman, Björn, Professor