Figure 3.2. The insecticidal carbamates were synthesized as analogues of physostigmine, the first carbamate, a toxic anticholinesterase alkaloid extracted from the calabar bean, the seed of the plant Physostigma venenosum.
Carbamates are absorbed dermally and from the gastrointestinal tract. They are also readily absorbed after inhalation at temperatures at which vapors are formed. The rate and extent of absorption depend on the vehicle; oil vehicles virtually double oral toxicity (Goncharova, 1968). LD50 values are far lower with parenteral than with oral administration (Rybakova, 1966; Yakim, 1967). Once absorbed, the carbamates are distributed rapidly to tissues. The rate of elimination differs by route of exposure, but labeled compound or metabolite can be detected in blood, urine, and feces.
Biotransformation of carbaryl has been reported to be similar in humans, rats, guinea pigs, monkeys, and sheep, with the major difference being the extent to which carbaryl is hydrolyzed to yield 1-naphthol. It appears to be the primary metabolite (Baron, 1991). Other water-soluble metabolites, including unidentified conjugates that could be hydrolyzed by acid to thioethers, have been identified in the urine and bile of rats that received intravenous or intraperitoneal ring- or carbonyl-labeled carbaryl. In a study of rats, those metabolites accounted for up to 32% of the dose secreted in bile. Some evidence also suggests that carbaryl is oxidized to CO2 in rats, guinea pigs, and humans. Small quantities of some intermediate metabolites of carbaryl are excreted in cows’ milk.
Carbamate metabolism and excretion is relatively rapid. Mammals given naphthyl-labeled carbaryl, for example, excreted 68–74% of the label in urine and 2–11% in feces within 24 h of administration. Rats dosed with N-methyl[14C]carbaryl eliminated 12–24% of the label in exhaled air and 53–54% in urine within 48 h. In another experiment, rats given carbonyl-labeled carbaryl eliminated 34–45% of the label in urine and 8% in feces within 24 h of administration; 30% was exhaled as 14CO2 (see Baron, 1991 for review). Intratracheal instillation of radioactive carbaryl as an aerosol produced peak activity in blood within 2–5 min in rats; 90% of the radioactivity was recovered in urine and 2–5% in feces within 3 days. In a gavage study in mice, 69% of a dose of carbaryl was absorbed within 60 min, with a half-life (t1/2) for absorption of 17 min. Peak blood concentrations occurred within 35–40 min after administration. By 60 min after administration, 16.9% of the dose appeared in urine and 8.6% in exhaled CO2. In rats that received [14C]carbaryl by gavage, the percentage of the administered dose recovered per gram of tissue ranged from less than 0.1% to 0.4% after 11 h; the highest concentrations were in liver, kidneys, and fat. Following an acute oral exposure of rats to carbaryl, it could be detected in the liver, brain, and heart 48 h after exposure.