Detection of hepatocarcinogens by combination of liver micronucleus assay and histopathological examination in 2-week or 4-week repeated dose studies.

Background: Currently, revisions to the ICH S1 guidance on rodent carcinogenicity testing are being proposed. Application of this approach would reduce the use of animals in accordance with the 3Rs principles (reduce/refine/replace). The method would also shift resources to focus on more scientific mechanism-based carcinogenicity assessments and promote safe and ethical development of new small molecule pharmaceuticals.

Vascular smooth muscle lipofuscinosis occurring predominantly in veins of a cynomolgus monkey (Macaca fascicularis).

A 6-year-old male cynomolgus monkey showed chronic wasting. No gross abnormalities were observed in necropsy except for changes secondary to wasting. Microscopic examination revealed pigment granules deposition in systemic smooth muscles.

Needle-shaped amyloid deposition in rat mammary gland: evidence of a novel amyloid fibril protein.

Amyloidosis is an extremely rare event in rats. In this study, we report that lipopolysaccharide binding protein (LBP) is the most likely amyloidogenic protein in rat mammary amyloidosis. Histologically, corpora amylacea (CA) and stromal amyloid (SA) were observed in rat mammary glands, and needle-shaped amyloid (NA) was also observed on the surface or gap of CA and SA.

Jejunal fibroplasia in a rat.

A jejunal nodular mass was identified in an aging rat. Histologically, the boundaries between the lesion and surrounding normal tissue as well as between the inner circular muscle and outer longitudinal muscle were indistinct. The lesion consisted of abundant eosinophilic matrix and cells with a large round to oval nucleus and indistinct cytoplasm.

Lymphocytic adrenal medullitis and lymphocytic thyroiditis in a laboratory beagle dog.

Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the medulla of the bilateral adrenal glands was observed in an 18-month-old male laboratory beagle dog. It might be that the present lymphocytic adrenal medullitis is an autoimmune-mediated disease as the histological characteristics are consistent with an autoimmune pathogenesis. However, the actual cause remains unclear as the existence of serum autoantibodies against the adrenal medulla could not be confirmed.