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 neonatal and adult CD rats to manganese-induced neurotoxicity. Identical oral manganese chloride (MnCl(2)) doses (0, 25, or 50 mg kg(-1) body wt. day(-1)) were given to neonatal rats throughout lactation (i.e. from postnatal day (PND) 1 through 21) and to adult male rats for 21 consecutive days. The MnCl(2) doses administered to neonates were ca. 100-fold higher than those resulting from the consumption of an equivalent volume of rat's milk. Rats were assessed using similar behavioral and neurochemical evaluations. Several statistically significant changes occurred in Mn-exposed rats relative to control animals. Neonates given the high dose of MnCl(2) had reduced body weight gain. An increased pulse-elicited acoustic startle response amplitude was observed in neonates from both MnCl(2) treatment groups on PND 21. Increased striatal, 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-dose group only. Increased striatal, cerebellar and brain residue Mn concentrations were observed in adult rats from the high-dose group. Increased striatal 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 PND 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 neonates only). The results of our experiment suggest that neonates may be at greater risk for Mn-induced neurotoxicity when compared to adults receiving similar high oral levels of Mn.
Dorman
D C
DC
Chemical Industry Institute of Toxicology, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA.
Struve
M F
MF
Vitarella
D
D
Byerly
F L
FL
Goetz
J
J
Miller
R
R
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002712:Chlorides / Q000009:adverse effects* / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics; D017895:Manganese Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics; D020149:Manganese Poisoning / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects
D002395:Catecholamines; D002712:Chlorides; D017895:Manganese Compounds; D008345:Manganese; C025340:manganese chloride; D004298:Dopamine