Comparison of aldicarb and methamidophos neurotoxicity at different ages in the rat: Behavioral and biochemical parameters

Young organisms are often more sensitive to the toxic effects of pesticides , and this finding has spurred research on further characterization of this susceptibility. The neurotoxic effects of cholinesterase (ChE)-inhibiting pesticides are of particular concern for human health risk assessment due t o the widespread exposure potential in children. This study evaluated age-r elated differences in susceptibility for a carbamate (aldicarb) and an orga nophosphorus pesticide (methamidophos). Comparisons were made between prewe anling (Postnatal Day 17, PND17), postweanling (PND27), and adult (similar to PND70) male and female rats. All were acute studies using oral administr ation. Sensitivity was quantified by (1) determination of maximally-tolerat ed doses (MTDs); (2) measurement of brain and blood ChE inhibition; and (3) neurobehavioral evaluation using end points known to be sensitive indicato rs of exposure to anticholinesterases. MTD data showed that preweanling rat s were twice as sensitive as adults to aldicarb, but there was no different ial sensitivity to methamidophos. The dose- response data for brain ChE inh ibition followed a similar pattern of age-related differences, and similar levels of inhibition were measured at the MTD regardless of age. Dose-respo nse and time course studies of neurobehavioral end points indicated that di fferential effects due to age depend on the behavioral end point examined. Following aldicarb administration, the dose-response curves for a few end p oints overlapped; however, the young rats otherwise showed fewer signs of t oxicity than did the adults despite similar levels of brain ChE inhibition. Motor activity assessment showed that aldicarb did not produce any activit y depression in PND17 rats, whereas the data for the PND27 and adult rats o verlapped. With methamidophos, the dose-response curves for most end points for preweanling and adult rats were quite similar. Aldicarb-induced ChE in hibition was readily reversible in all age groups, whereas with methamidoph os, enzyme activity recovered more rapidly in the young. Most behavioral al terations had recovered by 24 h with either pesticide. The results of these studies indicate that (1) ChE-inhibiting pesticides are not all the same r egarding relative sensitivity of the young; (2) age-related differences wer e reflected in both the MTDs and degree of ChE inhibition; and (3) age-rela ted differences in neurobehavioral measures depended on the pesticide and o n the end points examined.