抄録
Background: In nonhuman primate pre- and postnatal development (PPND or ePPND) studies, evaluation of morphological development in infants provides crucial data to assess potential test article effects following in utero exposure.
Method: Macroscopic (external, skeletal [by radiography] and visceral) and histopathology data in control infant cynomolgus monkeys (Macaca fascicularis) obtained from PPND studies were summarized.
Results: No major external or visceral malformations were observed in any infant. The most common minor external and visceral findings were abrasion of eyelids (4.3%) and atelectasis (9.1%, only seen in stillborn infants), respectively. Frequently observed skeletal findings included metaphyseal sclerosis (10.2%), delayed/incomplete bone mineralization/ossification (9.0%), stair step to the cranial suture (3.0%), and skull malalignment (1.8%). Frequently observed histopathology findings (≥10%) at scheduled sacrifice included mononuclear cell infiltration in several tissue; extramedullary hematopoiesis in liver and lymph nodes (LN); mineralization in adrenal and ovary; increased lymphocytes/lymphoid follicle in LN and spleen; brown pigment/hemosiderin in LN; secondly follicle in ovary. Frequently observed findings in infants that were stillborn or euthanized because of declining health, or died included decreased cellularity in follicle/paracortex of LN and spleen; hemorrhage or mononuclear cell infiltration in several tissues; extramedullary hematopoiesis of liver and spleen; atelectasis, edema, eosinophil infiltration, and eosinophilic material in lung alveoli; hepatocellular vacuolization; congestion in lung and liver.
Conclusions: Incidence of major external or visceral malformations or significant radiographic findings was low in infant cynomolgus monkey. In general, common spontaneous histopathology findings in infants are comparable with that of the adult monkeys (Chamanza et al. 2010).
