NON-NEOPLASTIC LESIONS IN RODENT BIOASSAYS

Abstract

Non-neoplastic findings obtained by detailed pathological examination of treated rodents utilized in subchronic studies up to 13 weeks in duration can contribute in determining the toxicity of chemicals and evaluate organ-specific injury. Pharmacokinetic and metabolic data on test chemicals are essential in elucidating organ specificity, the significance of the adverse effects on vital cellular functions in target organs, and in differentiating between effects which are “pathological”, “pharmacological” or “adaptive” in nature.
Non-neoplastic lesions including proliferative changes observed in short- and mid-term studies (up to 26 weeks) may also provide a provisional basis for predicting tumor induction produced by prolonged exposure to test chemicals. Recent extensive work on the role of persistent, non-genotoxic tissue damage in rodents revealed that the carcinogenic potential of non-genotoxic chemicals might be considered to be conditional and the results of dose levels high enough to produce cell proliferation.
The complexity of the non-neoplastic findings in rodents is known to increase with age, especially after one year. For proper evaluation of these data, analysis of causative effects, morphogenesis of each non-neoplastic change, and factors influencing the occurrence of these lesions are useful. General aspects of the pathological significance of these organ-specific, systemic lesions as age-associated background findings could contribute to understanding the susceptibility to chemicals as influenced by age-related alterations including the neoplastic process, in terms of bio-mechanistic and pharmacokinetic parameters.