Comparison of in vivo cholinesterase inhibition in neonatal and adult rats by three organophosphorothioate insecticides.
Developing mammals are more sensitive than adults to a variety of organophosphorothioate insecticides (OPs), compounds which act in vivo by inhibition of cholinesterase (ChE). Little is known, however, regarding age-related differences in biochemical responses to these toxicants. The time course of ChE inhibition and recovery in whole brain was compared in neonatal (7 days of age) and adult (80-100 days of age) rats after treatment with maximal tolerated doses (MTDs) of either methyl parathion (MPS), parathion (PS) or chlorpyrifos (CPF). Neonatal rats were more sensitive than adults in all cases (MTDs for MPS, PS and CPF; neonates = 7.8, 2.1 and 45 mg/kg, s.c.; adults = 18, 18, and 279 mg/kg, s.c., respectively). In general, maximal brain ChE inhibition was similar (greater than 78%) in both age groups but ChE activity recovered faster in neonates. Plasma and erythrocyte ChE activities correlated relatively well (r = 0.794-0.943) with brain ChE activity in neonatal rats at all time points between 4 h and 7 days after treatment but similar correlations between circulating and brain ChE activities in adults were more variable (r = 0.211-0.917). The results indicate that neonatal rats are more sensitive to acute lethality from these compounds and that MTD exposures produce extensive brain ChE inhibition in both age groups. Significant inhibitor-related and age-related differences in the duration of ChE inhibition can ensue, however, following such OP exposures.
Pope
C N
CN
Department of Pharmacology and Toxicology, School of Pharmacy, Northeast Louisiana University, Monroe 71209.
Chakraborti
T K
TK
Chapman
M L
ML
Farrar
J D
JD
Arthun
D
D
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000032:analysis / Q000097:blood; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D008297:Male; D008743:Methyl Parathion / Q000633:toxicity*; D010278:Parathion / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D002800:Cholinesterase Inhibitors; D008743:Methyl Parathion; D010278:Parathion; D002802:Cholinesterases; D004390:Chlorpyrifos