Toxicokinetics - trdoer40207

conduction across myoneural junctions in skeletal muscle, and interference of

CNS synaptic transmission. The signs and symptoms of poisoning, which are the

same as those for the organophosphate insecticides, are typically cholinergic

with lacrimation, salivation, miosis, convulsion, and death. The associated

symptoms mimic the muscarinic, nicotinic, and CNS actions of acetylcholine and

the severity of the effects is dose-dependent.

Acute toxicities, represented by the oral LD50 in male rats, ranged from

0.8 mg/kg for aldicarb to 850 mg/kg for carbaryl (Klaassen, Amdur, and Doull

1986). Carbaryl is considered one of the least acutely toxic carbamate

insecticides. Long-term dietary exposures to carbaryl in rats resulted in kidney

and liver toxicity levels similar to those observed for rat cholinesterase inhibition

in a separate chronic study (IRIS 1997).

Carbaryl is teratogenic in several experimental animals with widely varying

no-observed effect levels. However, in most species, the doses for effects on

fetuses were near the maternal toxic doses. Although the lowest effect levels

were observed for dogs (a tenth of the toxic dose to the mother), these studies

were judged inappropriate for human health risk assessment because of

differences in the metabolism of carbaryl between dogs and humans (IRIS 1997).

Chronic toxicity test results indicate carbaryl as a potential carcinogen and

mutagen, while aldicarb has been indicated as a suspect mutagen (Briggs and

Council 1992). Carbaryl has not been evaluated by the USEPA for its human

carcinogenic potential.

Toxicokinetics

Organophosphates are absorbed by the respiratory tract, mucous membranes,

skin, and gastrointestinal tract. The carbamate insecticides are direct inhibitors

of acetylcholinesterase and do not require metabolic activation (Klaassen,

Amdur, and Doull 1986). Hydrolytic reactions result in metabolites that lack

anticholinesterase activity. Various oxidation steps are catalyzed by mixed

function oxidases. The products formed by these reactions are not always less

toxic than the parent compound (Klaassen, Amdur, and Doull 1986). Unlike the

organophosphates, the organocarbamates are reversible inhibitors of

cholinesterase, and their duration of action is relatively short. Atropine alone is

the recommended antidote for organocarbamate poisoning.

Ecological effects

Bees are extremely sensitive to the organocarbamate insecticides, which can

also disrupt schooling behavior of fish, and are considered teratogens in fish

(Briggs and Council 1992). Certain organocarbamates are toxic to earthworms

and invertebrate populations. Aldicarb is reported to be highly toxic to birds,

fish, and aquatic insects, while carbaryl is highly toxic to fish, crustaceans,

earthworms, aquatic worms, and aquatic insects (Briggs and Council 1992).

Neither aldicarb nor carbaryl are expected to bioconcentrate significantly in

aquatic organisms.

D55

Appendix D Toxicological Profiles