Carboxylesterase and A-esterase activities during maturation and aging: Relationship to the toxicity of chlorpyrifos and parathion in rats

Chlorpyrifos (CPF) and parathion (PS), two common organophosphorus (OP) pes ticides, exhibit higher acute toxicity in younger animals compared to adult s. Maturational differences in detoxification via carboxylesterases (CEs) a nd A-esterases (AEs) have been suggested as contributors to the higher sens itivity of younger animals to OP toxicants. AEs (e.g., chlorpyrifos oxonase and paraoxonase) catalytically inactivate while CEs stoichiometrically eli minate OP anticholinesterases. While earlier studies have reported a relati onship between the toxicity of some OP pesticides and the maturational prof ile of AEs and CEs, little information exists on the relative OP-toxicant s ensitivity and detoxification capacities of aged animals. In the present st udy, we investigated the relationship between toxicity of CPF and PS and th e activity of CEs and AEs in liver, plasma, and lung of neonatal (7 day), j uvenile (21-day), adult (3-month), and aged (24-month) Sprague Dawley rats. CE sensitivity in vitro to chlopyrifos oxonase and paraoxon was also evalu ated across age groups. Neonatal and juvenile rats were more sensitive than adults to the acute lethality of both CPF and PS. Aged rats exhibited simi lar sensitivity to CPF but were markedly more sensitive than adults to PS. Levels of CEs and AEs in neonatal and juvenile rats were significantly lowe r than in adult tissues. Aged rats showed similar levels of AEs in all tiss ues and CEs in liver and lung, but plasma CE levels were significantly lowe r (50%) when compared to the adult rats. There were no significant age-rela ted differences in in vitro sensitivity of CEs to either chlorpyrifos oxon or paraoxon in any tissues. In general, acute sensitivity (MTD) was highly correlated with age-related differences in both esterase activities across all 3 tissues with CPF, but only plasma carboxylesterase activity was highl y correlated with sensitivity to parathion. The results suggest that both c arboxylesterase and A-esterase activities can be correlated with acute sens itivity to CPF and PS, but that age-related differences in CE activity are probably more important in differential toxicity. Furthermore, plasma carbo xylesterase activity may play a more pivotal role in the differential sensi tivity to PS.