The Toxicologic Effects of the Carbamate Insecticide Aldicarb in Mammals: A Review

Risher, John F; Mink, Franklin L.; Stara, Jerry F.

doi:10.2307/3430304

Cited by 21 publications

(33 citation statements)

References 19 publications

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“…Methiocarb and carbaryl showed PXR, CAR and PPARα activities in reporter gene assays. It was reported that the inhibitory effects of aldicarb sulfoxide and sulfone against acetylcholinesterase were similar with those of aldicarb (Risher et al, 1987). We also observed in our study that the nuclear receptor activities of methiocarb were almost abrogated owing to conversion to its sulfoxide and sulfone metabolites.…”

Section: Discussionsupporting

confidence: 85%

“…Aldicarb is easily oxidized to aldicarb sulfoxide but the formation of aldicarb sulfone by rat and pig liver microsomes was found to be negligible or very low (Pelekis and Krishnan, 1997;Montesissa et al, 1994). However, aldicarb sulfone was also detected as a minor in vivo metabolite of aldicarb in rats and pigs (Risher et al, 1987;Montesissa et al, 1994). In plants, ethiofencarb is hydrolyzed to its phenol derivative, converted to the sulfoxide, and then slowly to the sulfone (Cabras et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…Carbamates are hydrolyzed in plasma. The oxidation of sulfur-containing carbamates such as ethiofencarb, methiocarb, and aldicarb to sulfoxide derivatives is a well-known pathway (Montesissa et al, 1994;Pelekis and Krishnan, 1997;Risher et al, 1987), reportedly catalyzed by cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) (Buronfosse et al, 1995;Furnes and Schlenk, 2005;Schlenk et al, 2002;Usmani et al, 2004;Hajjar and Hodgson, 1980). However, the metabolic fate of the sulfoxide formed has not been extensively investigated.…”

Section: Introductionmentioning

confidence: 99%

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Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

et al. 2016

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-The oxidative, reductive, and hydrolytic metabolism of methiocarb and the hydrolytic metabolism of carbaryl by liver microsomes and plasma of rats or humans were examined. The effects of the metabolism of methiocarb and carbaryl on their nuclear receptor activities were also examined. When methiocarb was incubated with rat liver microsomes in the presence of NADPH, methiocarb sulfoxide, and a novel metabolite, methiocarb sulfone were detected. Methiocarb sulfoxide was oxidized to the sulfone by liver microsomes and reduced back to methiocarb by liver cytosol. Thus, the interconversion between methiocarb and the sulfoxide was found to be a new metabolic pathway for methiocarb by liver microsomes. The product of methiocarb hydrolysis, which is methylthio-3,5-xylenol (MX), was also oxidized to sulfoxide form by rat liver microsomes. The oxidations were catalyzed by human flavincontaining monooxygenase isoform (FMO1). CYP2C19, which is a human cytochrome P450 (CYP) isoform, catalyzed the sulfoxidations of methiocarb and MX, while CYP1A2 also exhibited oxidase activity toward MX. Methiocarb and carbaryl were not enzymatically hydrolyzed by the liver microsomes, but they were mainly hydrolyzed by plasma and albumin to MX and 1-naphthol, respectively. Both methiocarb and carbaryl exhibited PXR and PPARα agonistic activities; however, methiocarb sulfoxide and sulfone showed markedly reduced activities. In fact, when methiocarb was incubated with liver microsomes, the receptor activities were decreased. In contrast, MX and 1-naphthol showed nuclear receptor activities equivalent to those of their parent carbamates. Thus, the hydrolysis of methiocarb and carbaryl and the oxidation of methiocarb markedly modified their nuclear receptor activities.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

et al. 2016

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“…Their widespread and indiscriminate application poses serious health hazard to humans and animals (1). Carbamates have been reported to have high mammalian toxicity, and the main target organs are brain, liver, skeletal muscles, and heart (2,3). Their primary mechanism of toxicity is the reversible inhibition of serine group of acetylcholinesterase via carbamoylation at the nerve terminals (4).…”

Section: Introductionmentioning

confidence: 99%

Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats

Kumar

Gupta

et al. 2009

Indian J Clin Biochem

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“…Studies on chronic exposure to carbamate insecticides and case reports of long-term exposure give equivocal results. Some show no effects after chronic exposure (Risher et al, 1987), whereas others describe memory impairment (Dési et al, 1974;Ruppert et al, 1983;Ecobichon, 2001), degenerative polyneuropathy (Umehara et al, 1991), neurobehavioral effects (Moser, 1999), and other neurological disorders (Dési et al, 1974;Dickoff et al, 1987). An extensive survey of the toxicology of the common insecticide carbaryl reports a variety of reversible neurobehavioral and neurotoxic effects in vertebrates, all associated with acute poisoning symptoms (Cranmer, 1986).…”

Section: Introductionmentioning

confidence: 99%

Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain acetylcholinesterase

Smulders

Bueters²,

Kleef

et al. 2003

Toxicology and Applied Pharmacology

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Effects of commonly used carbamate pesticides on rat neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique. The potencies of these effects have been compared to the potencies of the carbamates to inhibit rat brain acetylcholinesterase. The potency order of six carbamates to inhibit ␣4␤4 nicotinic receptors is fenoxycarb Ͼ EPTC Ͼ carbaryl, bendiocarb Ͼ propoxur Ͼ aldicarb with IC50 values ranging from 3 M for fenoxycarb to 165 M for propoxur and Ͼ1 mM for aldicarb. Conversely, the potency order of these carbamates to inhibit rat brain acetylcholinesterase is bendiocarb Ͼ propoxur, aldicarb Ͼ carbaryl Ͼ Ͼ EPTC, fenoxycarb with IC50 values ranging from 1 M for bendiocarb to 17 M for carbaryl and Ͼ Ͼ1 mM for EPTC and fenoxycarb. The ␣4␤2, ␣3␤4, and ␣3␤2 nicotinic acetylcholine receptors are inhibited by fenoxycarb, EPTC, and carbaryl with potency orders similar to that for ␣4␤4 receptors. Comparing the potencies of inhibition of the distinct subtypes of nicotinic acetylcholine receptors shows that the ␣3␤2 receptor is less sensitive to inhibition by fenoxycarb and EPTC. The potency of inhibition depends on the carbamate as well as on a combination of ␣ and ␤ subunit properties. It is concluded that carbamate pesticides affect different subtypes of neuronal nicotinic receptors independently of acetylcholinesterase inhibition. This implicates that neuronal nicotinic receptors are additional targets for some carbamate pesticides and that these receptors may contribute to carbamate pesticide toxicology, especially after long-term exposure.

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The Toxicologic Effects of the Carbamate Insecticide Aldicarb in Mammals: A Review

Cited by 21 publications

References 19 publications

Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats

Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain acetylcholinesterase

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