Neurotoxicity of manganese chloride in neonatal and adult CD rats following subchronic (21-day) high-dose oral exposure

The purpose of this study was to evaluate the relative sensitivity of neona tal and adult CD rats to manganese-induced neurotoxicity, Identical oral ma nganese chloride (MnCl2) doses (0, 25, or 50 mg kg(-1) body wt. day(-1)) we re given to neonatal rats throughout lactation (i.e. from postnatal day (PN D) 1 through 21) and to adult male rats for 21 consecutive days. The MnCl2 doses administered to neonates were ca, 100-fold higher than those resultin g from the consumption of an equivalent volume of rat's milk. Rats were ass essed using similar behavioral and neurochemical evaluations. Several stati stically significant changes occurred in Mn-exposed rats relative to contro l animals. Neonates given the high dose of MnCl2 had reduced body weight ga in. An increased pulse-elicited acoustic startle response amplitude was obs erved in neonates from both MnCl2 treatment groups on PND 21. Increased str iatal, hippocampal, hindbrain and cortical Mn concentrations were observed in all Mn-exposed neonates on PND 21. Increased hypothalamic and cerebellar Mn concentrations were also observed on PND 21 in neonates from the high-d ose group only. Increased striatal, cerebellar and brain residue Mn concent rations were observed in adult rats from the high-dose group. Increased str iatal dopamine and 3,4-dihydroxyphenylacetic acid levels were observed only in PND 21 neonates from the high-dose group, No treatment-related changes were observed in clinical signs, motor activity (assessed in neonates on PN D 13, 17, 21 +/- 1 and in adults), passive avoidance (assessed in neonates on PND 20 +/- 1 and in adults) or neuropathology (assessed in PND 21 neonat es only). The results of our experiment suggest that neonates may be at gre ater risk for Mn-induced neurotoxicity when compared to adults receiving si milar high oral levels of Mn. Copyright (C) 2000 John Wiley & Sons, Ltd.