Six Week Study of Santicizer 160 Plasticizer Administered in the Feed to Sprague Dawley Rats: Neuropathological Study (final Report)

摘要

Subchronic neurotoxic effects were evaluated in groups of 10 Sprague-Dawley rats (5 male and 5 female) which had ingested butyl benzyl phthalate at nominal concentrations of 500,1500 or 3000 mg/kg in the diet for 6 weeks in a previous subchronic study. Signs of neurological impairment were not found in any of the animals received for evaluation. Body weights of males in the 500 mg/kg dose group were reduced by 7.5% when compared to control animals; body weight reductions were 8.5% for males in the 1500 mg/kg dose group, and 37% for males in the 3000 mg/kg dose group. Body weights of females in the 1500 mg/kg dose group were reduced by 8.5% when compared to control animals; body weight reduction was 12% for females in the 3000 mg/kg dose group. Microscopic histopathological evaluation was performed in tissue samples taken from the following areas: tibial nerve at the ankle, tibial nerve branches to the calf musculature (teased fiber), tibial nerve at the branching site, two levels of sciatic nerve (at mid-thigh and sciatic notch), selected lumbar dorsal root ganglion, selected lumbar dorsal and ventral roots, lumbar spinal cord at swelling, mid-thoracic spinal cord, cervical spinal cord at swelling, medulla oblongata, cerebellar vermis, lateral geniculate,and optic nerve at the chiasm. No remarkable change was observed in tissues taken from the peripheral nervous system in any animal at any dose level. One male animal treated at 1500 mg/kg displayed axonal swellings in the gracile nucleus of the medulla oblongata to a significant degree, although this effect was also observed in a control animal. A hamartoma-like lesion with associated pathological changes in the cerebellar vermis was observed in one male in the 500 mg/kg dose group, and scattered nerve fiber abnormalities were observed in the thoracic region of the spinal cord taken from another male in the 3000 mg/kg dose group;however, the investigators did not attribute these changes to the effect of the test article.