Time-course, dose-response, and age comparative sensitivity of N-methyl carbamates in rats

N-Methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterase (ChE). Despite their widespread use, there are few studies of neurotoxicity in young animals. To study potential age-related differences, we evaluated seven carbamates (carbaryl, carbofuran, formetanate, methiocarb, methomyl, oxamyl, and propoxur) in preweanling (17 days old or postnatal day [PND] 17) male rats. Motor activity was monitored, and ChE inhibition was measured in brain and red blood cells (RBCs) using a radiometric assay that minimized reactivation of ChE. First, we conducted time-course studies in PND17 Long-Evans male rats, using a single oral dose of each carbamate. Almost all carbamates showed maximal ChE inhibition at a 45-min time point; only methomyl showed an earlier peak effect (15 min). At 24 h, most inhibition had recovered. Next, dose-response data were collected for each carbamate, using four doses and control, with motor activity testing beginning 15 min after dosing and tissue collection at 40-45 min. RBC ChE was generally inhibited to a greater degree than brain. Motor activity was not as sensitive a measure for some of the carbamates, with some differences across carbamates in the shapes of the dose-response curves. Additional studies documented age-related differences by comparing ChE inhibition in PND11, PND17, and adult rats following administration of carbaryl or carbofuran. Only the youngest (PND11) rats were more sensitive than adults to carbaryl, but both younger ages showed more effects than adults with carbofuran. Comparisons of the other carbamates to previous studies in adult rats suggest similar age-related sensitivity. Thus, these data show the time-course and dose-response characteristics for each carbamate and document greater sensitivity of the young for carbofuran and carbaryl.