Noncatalytic detoxication of six organophosphorus compounds by rat liver homogenates

Tissue-Specific Effects of Chlorpyrifos on Carboxylesterase and Cholinesterase Activity in Adult Rats: An in Vitro and in Vivo Comparison

“…Since that time, many groups have investigated the possible role of CaE in antiChE toxicity. It is now clear that CaE is capable of altering the toxicity profile of many nerve agents (Clement, 1984a,b;Fonnum et al, 1985;Gupta and Dettbarn, 1987;Jimmerson et al, 1989;Purshottam and Srivastava, 1989;Clement and Erhardt, 1990;Maxwell, 1992aMaxwell, , 1987a and some anticholinesterase pesticides (e.g., Gupta and Kadel, 1989;Chambers et al, 1990;Gupta and Dettbarn, 1993).…”

“…The literature proposes two main hypotheses: (1) the effectiveness of the CaE in any given tissue is primarily due to the number of CaE molecules relative to the number of pesticide molecules, i.e., what proportion of the dose can be removed by binding to CaEs (Junge and Krisch, 1975;Maxwell, 1992a) or (2) the effectiveness is determined by the affinity of the CaE for a given pesticide (Chambers et al, 1990;Chambers and Carr, 1993). In their 1993 study comparing the toxicity profiles of three organophosphate pesticides in whole organisms, Chambers and Carr concluded that the in vitro enzyme sensitivities can predict the patterns of in vivo enzyme inhibition after exposure to these organophosphorus compounds.…”

Acute toxicity and effect of fenitrothion on liver esterase of fish

“…Other studies similarly concluded that AliE (eserin insensitive Besterases) are an important alternate phosphorylation site for OPs and reduce the concentration inhibition of acetylcholinesterase (AchE) (Funnum and Sterri, 1981;Maxwell et al, 1988). Chambers et al (1990) investigated detoxification of the oxons of six phosphorothionate insecticides (methyl parathion, parathion, chlorpyrifos-methyl, chlorpyrifos, EPN and leptophos) in rats and arrived at a similar conclusion. In addition, they stated that the presence of AliE in the liver, in close proximity to where much oxon would be generated by mixed function oxidase (MFO) (cytochrome P-450) -mediated desulfuration reaction, would allow them the opportunity to be readily phosphorylate and prevent much of the hepatically generated oxon from entering the circulation.…”

“…Chambers et al (1990) stated that, inhibition of LEs is mainly due to phosphorylation of aliesterases by OP compounds. Moreover, liver aliesterases occupy an alternative phosphorylation site for OPs and are capable of appreciably reducing the concentration of OPs required to inhibit the AchE.…”

“…This toxicity difference observed between the two species may be caused by several factors combined together. According to Chambers et al (1990), the acute toxicity of any poison is governed by its inherent potency at the target site and the effective concentration reaching that target. Moreover, factors such as the ability of noncatalytic detoxification, AchE sensitivity, rate of phosphorothionate activation, and the rate of catalytic detoxification can determine the phosphorothionate's acute toxicity level.…”