Batch safety tests (BSTs) of veterinary vaccines are conducted using small laboratory
animals to assure the safety of vaccines according to several criteria, including clinical
signs and change in body weight. Although the latter is used as an evaluation index in
BSTs, there have been no reports on the internal changes that affect body weight during
the test period. Therefore, we analyzed BST via pathological examination of the tested
animals. Here, BSTs were performed for 176 batches using mice and 126 batches using of
guinea pigs. Most of the gross findings could be classified into four lesion types
(nodules, adhesions, ascites, no apparent signs), with only one vaccine inducing lesions
that could not be classified into any of these four types. Histopathological examination
revealed that the reactions caused by BST were pyogenic and/or granulomatous inflammation.
Nodular or adhesive lesions comprised more severe pyogenic granulomatous inflammation than
ascites or cases with no apparent gross lesions. These nodular or adhesive lesions were
more frequently induced by vaccines that contained an adjuvant than by vaccines that did
not contain an adjuvant. The cases with “exceptional” gross findings histologically
presented severe necrosis of the hematopoietic system. Additional testing showed that
these “exceptional” lesions were induced when a specific type of light liquid paraffin was
injected along with other vaccine additives. Our results show that body weight loss and/or
lesions during BST were induced by proinflammatory properties of the tested vaccines and
that BST is a sensitive method for detecting unexpected effects of vaccine components.