Absorption, Distribution and Excretion
This study used rat and human skin for in vitro skin permeability tests. Results showed that rat skin permeable to carbaryl was 2.8 times greater than human skin. Excretion—48 hours after intraperitoneal injection of carbaryl labeled at three different locations in rats, its retention in vivo was investigated. 65% of the carbonyl-14C in carbaryl was excreted in urine, 25% in exhaled air, 2% in feces, and 10% remained in the body. The highest concentrations of 14C were found in the liver, kidneys, heart, and blood cells (red and white blood cells). 58% of the (14)C in N-methyl-(14)C-carbaryl is excreted in urine, 12% in exhaled air, 4% in feces, and 13% is retained… The highest concentrations of (14)C are found in organs with high blood flow, such as the liver, kidneys, heart, lungs, and spleen. 77% of the (14)C in naphthyl-(14)C-carbaryl is excreted in urine, 9% in feces, and 7% is retained… The highest concentrations of (14)C are found in the kidneys, spleen, bones, and adipose tissue… Approximately 50% of the (14)C is excreted within 4 hours… After oral administration of (1-naphthyl-1-(14)C)-N-methylcarbamate to rats, 53% and 82% were absorbed at 20 minutes and 1 hour, respectively. Carbaryl is absorbed very rapidly through the lungs, 2.5 times faster than through the small intestine.
N-methyl-labeled (14)C-carbarine was found in the fetuses of pregnant rats and mice. ...Autoradiography of (14)C-methylcarbarine in pregnant rats showed that the radiolabeled substance was localized in the fetal eyes, liver, and brain.
For more complete data on the absorption, distribution, and excretion of carbarine (9 in total), please visit the HSDB record page.

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Metabolism/Metabolites
(14)C-labeled carbarine is metabolized in insects, rats, and mouse, rat, and rabbit liver microsomes via aromatic hydroxylation, N-methyl hydroxylation, carbamoyl hydrolysis, and conjugation reactions. Of the metabolites identified in livestock products, five are considered important: carbaryl; 5,6-dihydro-5,6-dihydroxycarbaryl; 5-methoxy-6-hydroxycarbaryl; and all residues that can be hydrolyzed under acidic conditions to carbaryl, 5,6-dihydro-5,6-dihydroxycarbaryl, or 5-methoxy-6-hydroxycarbaryl. The U.S. Environmental Protection Agency (EPA) has included these compounds in its dietary risk assessment of carbaryl and reassessed the tolerance levels of carbaryl in livestock products. A single oral administration of carbaryl to rats was performed. Following urine extraction, column chromatography and thin-layer chromatography analysis preliminarily identified 1,5-naphthyldiol, along with trace amounts of carbaryl, 5-hydroxycarbaryl, and N-hydroxymethylcarbaryl. The major metabolite was identified as 5,6-dihydro-5,6-dihydroxycarbazone, present in both free (1.4% of the dose) and glucuronide (10.5% of the dose) forms. Naphthyl glucuronide and sulfate were also observed. In rat urine, in addition to 1-naphthol, 1-naphthylmethylcarbamate N-glucuronide, 1-naphthylmethyliminocarbonate O-glucuronide, 4-(methylcarbamoyloxy)-1-naphthyl glucuronide, 1-naphthyl glucuronide, 1-naphthyl sulfate, 4-(methylcarbamoyloxy)-1-naphthyl sulfate, 3 unidentified compounds, and one compound believed to be 1-naphthyl N-hydroxymethylcarbamate were observed. Similar results were observed in guinea pigs. For more complete metabolite/metabolite data on carbazone (17 metabolites in total), please visit the HSDB record page.
The known human metabolites of carbaryl include 4-hydroxycarbaryl, carbaryl hydroxymethyl, and 5-hydroxycarbaryl.
Carbamates are enzymatically hydrolyzed in the liver; degradation products are excreted via the kidneys and liver. (L793)

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Biological half-life
……The half-life of carbaryl in the small intestine of fasting rats is 6.4 minutes, and the half-life in the lungs is 2.6 minutes.

Toxicity Summary
Food is the primary source of carbaryl intake for the general population. …The general population may be exposed to carbaryl during pest control operations in homes and recreational areas. Workers may be exposed to carbaryl during and after its production, formulation, packaging, transportation, storage, and application. …Industrial and agricultural workers may experience serious skin contact if protective measures are inadequate. Carbaryl is rapidly absorbed in the lungs and digestive tract. …The main metabolic pathways of carbaryl are cyclohydroxylation and hydrolysis. This results in the formation of various metabolites, which combine with other substances to form water-soluble sulfates, glucuronides, and thiourates, ultimately excreted in the urine. Hydrolysis produces 1-naphthol, carbon dioxide, and methylamine. Hydroxylation produces 4-hydroxycarbaryl, 5-hydroxycarbaryl, N-hydroxymethylcarbaryl, 5,6-dihydro-5,6-dihydroxycarbaryl, and 1,4-naphthyldiol. In humans, its main metabolite is 1-naphthol. Under normal exposure conditions, carbaryl is unlikely to accumulate in animals. Carbaryl is primarily excreted in urine because its hydrolysis product, 1-naphthol, is mainly detoxified into water-soluble conjugates. Enterohepatic circulation of carbaryl metabolites is also significant, especially after oral administration. …Small amounts of absorbed doses of carbaryl metabolites are also present in saliva and breast milk. …Acute toxicity is low in birds. …Carbaryl is highly toxic to bees and earthworms. …Acute toxicity…varies by species, formulation, and carrier. …Carbaryl is slightly irritating to the eyes, with very low or no sensitization. Carbaryl has low cumulative toxicity. Studies have shown that carbaryl can adversely affect reproduction and perinatal development in a variety of mammals. Reproductive effects include decreased fertility, reduced litter size, and lower postnatal survival. Developmental toxicity manifests as increased intrauterine mortality, lower fetal weight, and malformations. With a few exceptions, all adverse reproductive and developmental effects were observed only at doses that caused significant maternal toxicity, and in many cases, the mother was more sensitive to carbaryl than the embryo. Maternal toxicity effects included lethality, growth retardation, and dystocia. Current evidence suggests that carbaryl does not possess any DNA-damaging properties. Numerous bacterial gene mutation tests have yielded negative results. Existing databases do not support the hypothesis that carbaryl induces genetic alterations in humans. The carcinogenicity of cabbaryl has been confirmed in multiple rat and mouse studies. Most results were negative… Cabbaryl's effects on the nervous system are primarily related to cholinesterase inhibition and are usually transient… Cabbaryl has been reported to affect coagulation… Cabbaryl can bind to free amino acids in the blood. Cabbaryl has been reported to interfere with carbohydrate metabolism, protein synthesis, and hepatic detoxification in mammals. Cabbaryl is a weak inducer of hepatic microsomal drug metabolism activity… Cabbaryl has been reported to enhance gonadotropin function of the rat pituitary gland. Cabbaryl is an inhibitor of cholinesterase activity. This effect is dose-dependent and rapidly reversible… All identified carbaryl metabolites have significantly lower activity as cholinesterase inhibitors than carbaryl itself. Carbaryl is readily absorbed by the body via inhalation and oral administration, but less so via the skin. Since cholinesterase inhibition is the primary mechanism of action for carbaryl, the clinical manifestations of poisoning mainly include: increased bronchial secretions, excessive sweating, salivation, and lacrimation; miosis, bronchoconstriction, abdominal cramps (vomiting and diarrhea); bradycardia; fine muscle fasciculations (in severe cases, the diaphragm and respiratory muscles may also be affected); tachycardia; headache, dizziness, anxiety, confusion, convulsions, and coma; and respiratory depression. Symptoms of poisoning appear rapidly after absorption and disappear quickly after cessation of exposure. In cases of occupational overdose of carbaryl, mild symptoms appear long before a dangerous dose is absorbed, which is why severe cases of occupational carbaryl poisoning are rare. In agricultural applications, skin contact may play an important role. There have been reports of rashes following accidental splashes of carbaryl preparations. ... The most sensitive biomarkers for carbaryl exposure are the presence of 1-naphthol in urine and a decrease in cholinesterase activity in the blood. ... Due to carbaryl's low vapor pressure, rapid degradation, the rapid spontaneous recovery of inhibited cholinesterase, and the fact that symptoms usually appear before dangerous doses accumulate in the body, the risk of harm to humans from carbaryl is considered low. ... Carbaryl is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Carbamate compounds carbamate and acetylcholinesterase form unstable complexes with cholinesterase by carbamylation of the enzyme's active site. This inhibition is reversible. Cholinesterase inhibitors inhibit the activity of acetylcholinesterase. Because acetylcholinesterase has important physiological functions, chemicals that interfere with its activity are potent neurotoxins, causing excessive salivation and lacrimation even at low doses. High concentrations of exposure often cause symptoms such as headache, salivation, nausea, vomiting, abdominal pain, and diarrhea. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, which is released at the neuromuscular junction, causing muscle or organ relaxation. Inhibition of acetylcholinesterase results in the accumulation and sustained action of acetylcholine, leading to continuous nerve impulse transmission and an inability to stop muscle contraction.

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Toxicity Data
LD50: 230 mg/kg (oral, rat) (T14)
LD50: 4000 mg/kg (dermal, rat) (T14)
LD50: 64 mg/kg (intraperitoneal, rat) (T14)
LD50: 1400 mg/kg (subcutaneous, rat) (T14)
LD50: 41900 μg/kg (intravenous, rat) (T14)

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Interactions
Organophosphate and carbamate poisoning is a major cause of morbidity and mortality worldwide. Concerns have been raised regarding the safety and efficacy of oximes, such as pralidoxime (2-PAM), in patients with carbamate poisoning, particularly in those with carbaryl poisoning. This study aimed to evaluate the role of 2-PAM in a lethal carbaryl poisoning mouse model. …Female ICR Swiss albino mice weighing 25–30 g were acclimatized to the laboratory environment and housed under standard conditions. 110 mice were subcutaneously injected with the LD50 dose of carbaryl. Ten minutes later, the mice were randomly assigned to eight groups using a block randomization method: a saline control group, an atropine-only group, a 100 mg/kg 2-PAM group (with and without atropine), a 50 mg/kg 2-PAM group (with and without atropine), and a 25 mg/kg 2-PAM group (with and without atropine). All drugs were administered intraperitoneally, with a constant atropine dose of 4 mg/kg. The single objective endpoint was defined as 24-hour survival. Mortality rates were compared using the chi-square test or Fisher's exact test. ... After administration of the LD50 dose of carbaryl, 60% of the animals died. Atropine alone significantly improved survival (mortality rate 15%). High doses of 2-PAM (with or without atropine) were numerically worse, but not statistically different from the control group. Medium doses of 2-PAM were not different from the control group, but the addition of atropine improved survival (mortality rate 10%). Low doses of 2-PAM significantly improved survival (mortality rate 25%). Atropine further reduced mortality to 10%. ... When the dosage is appropriate, 2-PAM alone can protect mice from carbaryl poisoning. This benefit could not be confirmed in other models, possibly due to oxime overdose. This study investigated the pharmacokinetic and pharmacodynamic effects of carbaryl on isolated human erythrocytes (RBCs) and in four healthy subjects after oral administration of 1 mg/kg carbaryl (with or without carbaryl, 300 mg, eight times per hour for 3 days). Cabbaryl reduced isolated erythrocyte acetylcholinesterase activity in a concentration-dependent manner, achieving a 20% inhibition rate at 1 μg/mL. Carbaryl also inhibited erythrocyte acetylcholinesterase activity in a dose-dependent manner, but at concentrations 40 times higher than cabbaryl. At high concentrations, the inhibitory effect of carbaryl on erythrocyte acetylcholinesterase was additive, but had no effect at treatment-related concentrations (10 μg/mL). In normal subjects, after oral administration of cabbaryl, plasma concentrations rapidly increased to peak and then declined, with a half-life of 0.79 ± 0.47 hours. The clearance rate of oral cabbaryl was 5.4 ± 2.0 L/min. Peak plasma concentrations of carbaryl inhibited erythrocyte acetylcholinesterase activity by 27%, while the concentration required for 20% inhibition was 0.02 μg/mL. The terminal half-life of this dynamic response was 2.6 ± 1.5 h. Pretreatment with cimetidine doubled the peak plasma carbaryl concentration and decreased clearance (to 2.5 ± 1.5 L/min) (P < 0.05). However, the half-life remained unchanged. Despite increased carbaryl concentrations, the maximum inhibition of erythrocyte acetylcholinesterase activity was significantly reduced, with the carbaryl concentration required to achieve 20% inhibition increasing to approximately 0.5 μg/mL. These results are consistent with the hypothesis that carbaryl is metabolized by drug-metabolizing enzymes that can be inhibited by cimetidine.
Administration of 2-pyridinium oxime methyl chloride (2-PAMCl) is part of the standard treatment regimen for human overexposure to various organophosphorus pesticides and nerve agents. However, some literature indicates that poisoning from the commonly used insecticide carbaryl (1-naphthyl-N-methylcarbamate) can be exacerbated by administration of 2-PAM Cl. This effect has been reported in mice, rats, dogs, and humans. Several oxime compounds enhance the inhibitory effect of carbaryl on eel acetylcholinesterase (eel AChE, EC 3.1.1.7) and human serum cholinesterase (human BuChE, EC 3.1.1.8). Based on 95% confidence intervals, the order of enhancement of carbaryl on eel AChE is: TMB-4 = Toxogonin > HS-6 = HI-6 > 2-PAM Cl. Similarly, the order of enhancement of carbaryl on human BuChE is: TMB-4 > Toxogonin > HS-6 = 2-PAM Cl. Carbaryl sensitization mice also showed an enhancing effect, with TMB-4 exacerbating toxicity more than 2-PAM Cl. Our hypothesis is that certain oxime compounds act as allosteric effectors of cholinesterase in carbaryl poisoning, leading to enhanced inhibition rates and thus exacerbating carbaryl toxicity. The antidiuretic diazoxide…increased carbaryl toxicity in pigs by 20-fold. For more complete data on interactions of carbaryl (13 in total), please visit the HSDB record page. Non-human toxicity values: Oral LD50 in rats: 230 mg/kg; Dermal LD50 in rats: 4000 mg/kg; Intraperitoneal LD50 in rats: 64 mg/kg; Subcutaneous LD50 in rats: 1400 mg/kg. For more complete data on non-human toxicity values of carbaryl (10 in total), please visit the HSDB record page.

: Xiuyuan Z, Zhihong H, Lixia W, Xiaonan L. Construction of a Single Chain Variable Fragment Antibody (scFv) against Carbaryl and Its Interaction with Carbaryl. Biochemistry (Mosc). 2015 May;80(5):640-6.

According to the U.S. Environmental Protection Agency (EPA), carbaryl may be carcinogenic. According to the National Institute for Occupational Safety and Health (NIOSH), carbaryl may cause developmental toxicity, female reproductive toxicity, and male reproductive toxicity. Carbaryl is a white crystalline solid, insoluble in water, flammable but difficult to ignite. Inhalation (dust, etc.) is toxic. Combustion produces toxic nitrogen oxides. Carbaryl is a carbamate formed by the condensation of 1-naphthol and methylcarbamate. It is used as an EC 3.1.1.7 (acetylcholinesterase) inhibitor, carbamate insecticide, EC 3.1.1.8 (cholinesterase) inhibitor, acaricide, agrochemical, and plant growth inhibitor. It is a carbamate belonging to the naphthalene family of compounds. Carbaryl is functionally related to methylcarbamate and 1-naphthol. Carbaryl is an insecticide used on a variety of crops. Occupational exposure to carbaryl in humans has been observed to cause cholinesterase inhibition, and decreased levels of this enzyme in the blood can cause neurological symptoms. These symptoms appear to be reversible upon cessation of exposure. Long-term low-dose exposure to carbaryl can lead to cholinesterase inhibition, resulting in headaches, memory loss, muscle weakness and cramps, and anorexia. The U.S. Environmental Protection Agency (EPA) has classified carbaryl as a Group D substance, meaning its carcinogenicity in humans cannot be determined. Carbaryl is a synthetic carbamate acetylcholinesterase inhibitor, suspected of being an endocrine disruptor, and is used as an insecticide. It is a toxic, odorless, grayish-white solid that can be exposed through inhalation, ingestion, or contact. Carbaryl is a carbamate insecticide. Carbamate insecticides are derived from carbamic acid and work similarly to organophosphate insecticides. They are widely used in homes, gardens, and agriculture. The first carbamate insecticide, carbaryl, was introduced in 1956, and its global usage exceeds that of all other carbamate insecticides combined. Sevin is widely used in lawns and gardens due to its relatively low oral and dermal toxicity to mammals and its broad spectrum of application. Most carbamate insecticides are highly toxic to hymenoptera, requiring precautions to prevent contact with foraging insects such as bees or parasitic wasps. Some carbamate insecticides can be transported within plants, making them effective systemic agents. (L795)
A carbamate insecticide and parasiteicide. It is a potent cholinesterase inhibitor, belonging to the reversible cholinesterase inhibitor class of carbamates. It has extremely low toxicity through dermal absorption and is used in some countries for head lice control.

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Therapeutic Uses
Sevin formulations have been successfully used to control human lice.
/Veterinary Use/ Used to control fleas, lice, ticks, and mites on animals, poultry, and premises, including buffalo scabies; lice, ticks, and scabies mites on cattle; fleas and drug-resistant fleas on dogs; and mites, lice, and fleas on poultry.
Pharmaceuticals (Veterinary): External Parasite Killer

C12H11NO2

201.22124

201.078

63-25-2

Carbaryl-d3;1433961-56-8;Carbaryl-d7;362049-56-7

6129

Colorless to light tan crystals
White or gray ... solid.

1.1±0.1 g/cm3

366.5±25.0 °C at 760 mmHg

142-146 °C(lit.)

175.4±23.2 °C

0.0±0.9 mmHg at 25°C

1.570

3.35

1

2

2

15

230

0

CNC(OC1=CC=CC2=CC=CC=C21)=O

CVXBEEMKQHEXEN-UHFFFAOYSA-N

InChI=1S/C12H11NO2/c1-13-12(14)15-11-8-4-6-9-5-2-3-7-10(9)11/h2-8H,1H3,(H,13,14)

1-Naphthalenol, 1-(N-methylcarbamate)

Arilat Arilate Arylam Atoxan Bercema NMC50 NMC-50 NMC 50

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~496.97 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)