Inhibitor Report for: Tolclofos-methyl

Biomimetic oxidation mediated by three types of iron porphyrins was examined for five organophosphrus pesticides, fenitrothion (I), cyanophos (II), tolclofos-methyl (III), butamifos (IV) and fenthion (V). The major products from I-IV were the corresponding phenols and each oxon formed via a phosphoxathiirane intermediate by oxidation at the P=S moiety similarly as reported for their mammalian metabolism by cytochrome P450 enzymes. Stepwise oxidation of the methylthio sulfur via sulfoxide to sulfone, and ester cleavage and oxidative desulfuration primarily proceeded for V. Both the electron distribution of the highest occupied molecular orbital and its energy level of the pesticides calculated by MNDO-PM3 were shown to control the reaction site and rate of oxidation at sulfur atoms.

This research evaluated exposure pathways across work tasks for three organophosphate pesticides in a group of greenhouse workers. During reentry in ornamental plant greenhouses, five male workers were monitored for five consecutive days. Skin contamination (excluding hands) was evaluated with nine pads of filter paper placed on the skin. Hand contamination was assessed by washing with 95% ethanol. Respiratory exposure was evaluated by personal air sampling. The respiratory dose was based on a lung ventilation of 20 L/min. The doses absorbed were estimated assuming 10% skin penetration and 100% lung retention. Urinary alkylphosphates were assayed in the 24-hour urine samples of the days on which exposure was evaluated. Respiratory exposure was usually less than skin contamination, being 4.5 +/- 8.4%, 9.9 +/- 10.0%, and 49.5 +/- 26.6% (mean +/- standard deviation) of total exposure for omethoate, tolclofos-methyl, and fenitrothion, respectively. Multiple regression analysis showed that urinary alkylphosphate (nmol/24 hours) (y) was significantly correlated (r = 0.716, p < 0.001) with the respiratory doses of the three active ingredients absorbed the same day (x1) and with the cutaneous dose absorbed the previous day (x2). The relationship was expressed by the equation y = 0.592x2 + 0.117x, + 156.364. The doses of omethoate absorbed by one worker were more than 45 times the acceptable daily intake (ADI) of 1.41 nmol/kg body weight (b.w.) The ADI for fenitrothion and tolclofos-methyl (10.8 and 212.6 nmol/kg body weight, respectively) were never exceeded. High absorption by one worker underlines the importance of correct use of protective clothing. In this study the hands were always a source of contact with the pesticides. Greater precautions should be taken to reduce contamination (clean gloves, constant use of gloves).

We investigated the spontaneous reactivation of mouse plasma cholinesterase (ChE) after inhibition by various organophosphorus compounds. The remarkable spontaneous reactivations during storage at 24 degrees C were observed in plasma ChE prepared 30 min after oral administration of three O,O-dimethyl organophosphorus compounds, i.e. malathion, methylparathion and cyanox; while the spontaneous reactivation did not occur after inhibition by tolclofos-methyl, one of O,O-dimethyl organophosphorus compounds. The plasma ChEs inhibited by surecide, salithion and leptophos, which contain no O,O-dimethyl moiety, were not reactivated or only slightly so. These results suggest that a more sufficient attention should be paid in the determination of activity of plasma ChE inhibited by O,O-dimethyl organophosphorus compounds than that of plasma ChE inhibited by organophosphorus compounds without O,O-dimethyl moiety, since plasma ChE inhibited by the organophosphorus compounds with O,O-dimethyl moiety, except for tolclofos-methyl, was more easily reactivated, and the correct activity of inhibited plasma ChE can not be obtained without attention to the spontaneous reactivation. Furthermore, these spontaneous reactivations were examined by using butyrylthiocholine as well as acetylthiocholine as a substrate, and results showed that there was little difference between the spontaneous reactivations observed in using acetylthiocholine and butyrylthiocholine. So, it is concluded that these spontaneous reactivations take place only in pseudo ChE.