Analysis of fighting-associated wounds causing death of young male CD-1 mice in carcinogenicity studies

Abstract

Early death of CD-1 mice due to fighting-associated wounds was analysed using information gathered from the control groups of twenty mouse carcinogenicity studies, all deaths occurring within the first 50 weeks of the studies being reviewed. Of the 1453 mice in each sex, 101 (6.95 %) male and 69 (4.75%) female decedents with a statistical significance (p=0.016), in favour of females, were recorded during the first 50 weeks of study. The hazard ratio for gender was found to be 1.45. Analysis of factors contributing to death revealed that 26 (25.7%) males had integumentary wounds, 27 (26.7%), males exhibited neoplastic lesions, and 48 (47.5%) males had other changes. In females, the figures were 11 (15.9%), 28 (40.6%), and 30 (43.4%), respectively. A high proportion of the observed lesions such as ulceration, abscess-formation and granulomatous inflammation of the skin, subcutaneous tissues or muscle, were considered to be fighting-associated wounds. Of the neoplastic causes of death, haematopoietic tumours were the most common, followed by osteosarcoma, and some skin or mammary tumours. One of the most common nontumour factors contributing to death was kidney diseases (nephropathy and glomerulonephritis), followed by urinary obstruction of males. Some animals died from trauma/fracture, dosing accidents, unknown reasons or were also sacrificed due to poor clinical condition. From the mortality analysis of fighting-associated factors contributing to death, there was no significant statistical difference (p values, males=0.55, females=0.94) between single and multiple housed animals. In the hazard ratio analysis between single and multiple housing, multiple housed males have 1.32 times the risk of death when compared with single housed males, whereas this figure in females were found to be 1.05. In conclusion, housing density, especially in males, had an impact on survival; however, it could not be attributed solely to fighting-associated integumentary lesions.