Carbaryl cholinesterase inhibition

Rosenfeld and Kilsheimer (1974) prepared several 2,2,2-trifluoroacetophenone oxime methylcarbamates substituted on the ring. Among these, o-methoxy-2,2,2-trifluoroacetophenone oxime N-methylcarbamate (54) and o-fluoro-2,2,2-tri-fluoroacetophenone oxime N-methylcarbamate (55) are the most efficient. Their insecticidal action is nearly identical to that of carbaryl (3), white their cholinesterase-inhibiting effect surpasses substantially that of carbaryl. 

Dermal dose-ChE response and percutaneous absorption studies were conducted with parathion, carbaryl, and thiodicarb in the rat. Parathion and thiodicarb inhibited 50% of the red cell cholinesterase activity at dose levels of 3.2 and 33 mg/kg of bw. Carbaryl at the highest dose level tested (417 mg/kg of bw) produced no detectable red cell cholinesterase Inhibition. 

The use of carbaryl has not resulted in illnesses among workers mixing-loading or applying the pesticide and no reentry interval has been established for this pesticide in California. Cholinesterase inhibition is considered to be the major toxic effect of carbaryl. Carbaryl (500 mg/kg) topically applied to the back of the rabbit inhibited 50% of the red cell ChE activity 24 hr after application and activity returned to pretreatment values after 72 hr (21). In the rat study reviewed in this paper, a topical dose of 417 mg/kg did not produce ChE inhibition 24 hr after application indicating that the rate of absorption was low or carbaryl was metabolized in the skin to non-OiE inhibiting products. 

The design and implementation of a portable fiber-optic cholinesterase biosensor for the detection and determination of pesticides carbaryl and dichlorvos was presented by Andreou81. The sensing bioactive material was a three-layer sandwich. The enzyme cholinesterase was immobilized on the outer layer, consisting of hydrophilic modified polyvinylidenefluoride membrane. The membrane was in contact with an intermediate sol-gel layer that incorporated bromocresol purple, deposited on an inner disk. The sensor operated in a static mode at room temperature and the rate of the inhibited reaction served as an analytical signal. This method was successfully applied to the direct analysis of natural water samples (detection and determination of these pesticides), without sample pretreatment, and since the biosensor setup is fully portable (in a small case), it is suitable for in-field use. 

The general chemical structure of N-methyl carbamate is shown in Fig. 4.4. Common N-methyl carbamates in use today include aldicarb, carbofuran, methiocarb, oxamyl, and carbaryl. N-methyl carbamates share with organophosphates the capacity to inhibit cholinesterase enzymes and, therefore, share similar symptomology during acute and chronic exposure. 

Carbamates, first synthesized in the 1930s and commercialized in the 1960s, constitute the most recently developed class of anticholinesterase insecticides. Developed to replace the more dangerous CH and OP insecticides, their toxic principle derived from the effects on humans of the Calabar bean used in the West African trial by ordeal (Ecobichon 1997). Carbamates inhibit nervous tissue cholinesterases, but less irreversibly than OP insecticides, resulting in reduced toxicity (Ecobichon 1997). Common carbamate names include carbaryl, methomyl, and maneb. 

The effect of a topically applied dose of parathion, carbaryl, and thiodicarb on red blood cell cholinesterase activity in the rat was reviewed along with pharmacokinectic data developed on their percutaneous absorption. Parathion and thiodicarb inhibited 50% of the red cell cholinesterase activity at dose levels of 3.2 and 33 mg/kg of bw, while no inhibition was detected with carbaryl at dose levels as high as 417 mg/kg of w. Parathion and carbaryl were absorbed at 0.33 and 0.18 ug/hr/cm, while thiodicarb was absorbed at rates varying from 0.27 to 0.042 ug/hr/cm of skin. Skin loss and plasma elimination data were used to calculate the values. The topically applied pesticides slowly penetrated skin and were available for absorption into blood and redistribution to other tissues. Recovery data suggested that evaporative losses occurred during the course of the 5-day study. The pesticides may be removed from skin by washing, thus reducing the amount available for absorption. 

Various pharmaceuticals and biocides are derived from benzo[b]thiophene, being bioisosteric with naphthalene and indole. Mobam (16, 4-(N-methylcarbamoyl)benzo[b]-thiophene) is an insecticide which is as effective as carbaryl (17). Both compounds inhibit the enzyme acetyl cholinesterase. 

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