Absorption, Distribution and Excretion
An in vitro dermal penetration study was conducted using both rat and human skin . This study showed that rat skin was 2.8 times more permeable to carbaryl than human skin.
Excretion--retention of ... carbaryl labeled in 3 different positions ... studied 48 hr after ip admin to rats. 65% of (14)C of carbonyl-(14)C-carbaryl was excreted in urine, 25% in expired air, 2% in feces, & 10% was retained ... highest levels of (14)C were present in liver, kidneys, heart, & corpuscles (erythrocytes & leukocytes). 58% of (14)C of n-methyl-(14)C-carbaryl was excreted in urine, 12% in expired air, 4% in feces, & 13% was retained ... (14)C was maximal in liver, kidneys, heart, lungs, & spleen, organs with high blood flow. 77% of (14)C of naphthyl-(14)C-carbaryl was excreted in urine, 9% in feces, & 7% was retained ... levels of (14)C in tissue were highest in kidneys, spleen, bone, & fat ... about 50% of (14)C had been excreted in 4 hr ... .
Of oral dose of (1-naphthyl-1-(14)C)-N-methylcarbamate given to rats, 53% & 82% were absorbed after 20 min & 1 hr, respectively. Carbaryl is absorbed very rapidly from lung, 2.5 times faster than from small intestine.
(14)C-carbaryl labeled in n-methyl group has been found in fetuses of pregnant rats, & mice. ... Autoradiographic study of (14)C-methyl-carbaryl in pregnant rat has shown that radiolabel was localized in eye, liver, & brain of fetus.
For more Absorption, Distribution and Excretion (Complete) data for CARBARYL (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
Sevin, labeled with (14)C, is metabolized in insects, in rat, and by microsomal prepn of mouse, rat & rabbit liver, by aromatic hydroxylation, n-methyl hydroxylation, hydrolysis of carbamyl grouping, & by conjugation.
Of the metabolites identified in livestock commodities, five are considered significant ... : carbaryl; 5,6-dihydro-5,6-dihydroxy carbaryl; and 5-methoxy-6-hydroxy carbaryl and all residues which can be hydrolyzed to carbaryl, 5,6-dihydro-5,6-dihydroxy carbaryl, or 5-methoxy-6-hydroxy carbaryl under acidic conditions. The /EPA/ included these compounds in the dietary risk assessment for carbaryl, and in the reassessment of carbaryl tolerances for livestock commodities only.
Single oral dose of carbaryl was admin to rats. After extraction of ... urine, column & TLC chromotography, tentative identification was made for 1,5-naphthalenediol with small amt of carbaryl, 5-hydroxycarbaryl, & trace of n-hydroxymethylcarbaryl was also present. A major metab ... identified as 5,6-dihydro-5,6-dihydroxycarbaryl, was found free (1.4% of the dose) & as the glucuronide (10.5% of the dose). Naphthyl glucuronide & sulfate were also observed.
In urine of rats in addn to 1-naphthol, 1-naphthyl methylcarbamate N-glucuronide, 1-naphthyl methylimido-carbonate O-glucuronide, 4-(methylcarbamoyloxy)-1-naphthyl glucuronide, 1-naphthyl glucuronide, 1-naphthyl sulfate, 4-(methylcarbamoyloxy)-1-naphthyl sulfate, 3 unidentified cmpd & cmpd believed to be 1-naphthyl N-hydroxymethylcarbamate were observed. Similar results were observed with guinea pigs.
For more Metabolism/Metabolites (Complete) data for CARBARYL (17 total), please visit the HSDB record page.
Carbaryl has known human metabolites that include 4-hydroxycarbaryl, carbaryl methylol, and 5-hydroxycarbaryl.
The carbamates are hydrolyzed enzymatically by the liver; degradation products are excreted by the kidneys and the liver. (L793)

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Biological Half-Life
... The half-life of carbaryl was 6.4 min in the empty small intestines and 2.6 min in the lungs of rats.

Toxicity Summary
Food represents the major source of carbaryl intake for the general population. ... The general population can be exposed to carbaryl during pest control operations in both the home & recreation areas. Workers can be exposed to carbaryl during its manufacture, formulation, packing, transportation, storage, & during & after application. ... Significant dermal exposure may occur in industrial & agricultural workers if protective measures are inadequate. Carbaryl is rapidly absorbed in the lungs & digestive tract. ... The principal metabolic pathways of carbaryl are ring hydroxylation & hydrolysis. As a result, numerous metabolites are formed & subjected to conjugation with the formation of water-soluble sulfates, glucuronides, & mercapturates, excreted in the urine. Hydrolysis results in the formation of 1-naphthol, carbon dioxide & methylamine. Hydroxylation produces 4-hydroxycarbaryl, 5-hydroxycarbaryl, N-hydroxymethylcarbaryl, 5-6-dihydro-5-6-dihydroxycarbaryl & 1,4-naphthalendiol. The principal metabolite in humans is 1-naphthol. Under normal exposure conditions, the accumulation of carbaryl in animals is unlikely. Carbaryl is excreted primarily via the urine, since the product of its hydrolysis, 1-naphthol, is mainly detoxified to water-soluble conjugates. Enterohepatic cycling of carbaryl metabolites is also considerable, especially after oral administration. ... Carbaryl metabolites are also present in a small percentage of the absorbed doses in saliva & milk. ... The acute toxicity for birds is low. ... Carbaryl is very toxic for honey-bees & earthworms. ... The acute toxicity ... varies considerably according to species, formulation & vehicle. ... Carbaryl is a mild eye irritant & has little or no sensitizing potential. ... Carbaryl has a low cumulative potential. Carbaryl has been shown to affect mammalian reproduction & perinatal development adversely in a number of species. Effects on reproduction include impairment of fertility, decreased litter size, & reduced postnatal viability. Developmental toxicity is seen as increased in utero death, reduced fetal weight, & the occurrence of malformation. With the exception of a small number of studies, all adverse reproductive & developmental effects were noted only at doses that caused overt maternal toxicity, &, in a number of cases, the maternal animal was more sensitive to carbaryl than the conceptus. The maternal toxic effects included lethality, decreased growth, & dystocia. ...The available evidence indicates that carbaryl does not have any DNA-damaging properties. ... Negative results were obtained in tests for gene mutations in a large number of bacterial assays ... The available database does not support the presumption that carbaryl poses a risk of inducing genetic changes in ... humans. Carbaryl has been studied for its carcinogenic potential in numerous studies on rats & mice. The results of most of these studies were negative ... The effects of carbaryl on the nervous system are primarily related to cholinesterase inhibition & are usually transitory. ... Carbaryl has been reported to affect coagulation ... Carbaryl binds free blood amino acids. Disturbances have been reported in the carbohydrate metabolism & protein synthesis & detoxification function of the liver in mammals. Carbaryl is a weak inducer of hepatic microsomal drug-metabolizing activity. ... Carbaryl has been reported to incr the gonadotropic function of the hypophysis of rats. Carbaryl is an inhibitor of cholinesterase activity. This effect is dose-related & quickly reversible. ... All identified metabolites of carbaryl are appreciably less active cholinesterase inhibitors than carbaryl itself. Carbaryl is easily absorbed /in humans/ through inhalation & via the oral route & less readily by the dermal route. Since the inhibition of cholinesterase is the principal mechanism of carbaryl action, the clinical picture of intoxication is dominated by ... symptoms, such as: increased bronchial secretion, excessive sweating, salivation, & lacrimation; pinpoint pupils, bronchoconstriction, abdominal cramps (vomiting & diarrhea); bradycardia; fasciculation of fine muscles (in severe cases, diaphragm & respiratory muscles also involved); tachycardia; headache, dizziness, anxiety, mental confusion, convulsions, & coma; & depression of the respiratory center. Signs of intoxication develop quickly after absorption & disappear rapidly after exposure ends.... In cases of occupational overexposure to carbaryl, mild symptoms are observed long before a dangerous dose is absorbed, which is why severe cases of occupational intoxication with carbaryl are rare. During agricultural application, dermal exposure may play an important role. ... The appearance of a skin rash after accidental splashing with carbaryl formulations has been described. ... The most sensitive biological indicator of carbaryl exposure is the appearance of 1-naphthol in the urine & the decr of cholinesterase activity in the blood. ... The hazards of carbaryl for human beings are judged to be low, because of its low vapor pressure, rapid degradation , rapid spontaneous recovery of inhibited cholinesterase, & the fact that symptoms usually appear well before a dangerous dose has accumulated in the body. ...
Carbaril is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Carbamates form unstable complexes with chlolinesterases by carbamoylation of the active sites of the enzymes. This inhibition is reversible. A cholinesterase inhibitor suppresses the action of acetylcholine esterase. Because of its essential function, chemicals that interfere with the action of acetylcholine esterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.

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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: 41 900 ug/kg (Intravenous, Rat) (T14)

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Interactions
Poisoning from organophosphates and carbamates is a significant cause of morbidity and mortality worldwide. Concerns have been expressed over the safety and efficacy of the use of oximes such as pralidoxime (2-PAM) in patients with carbamate poisoning in general, and more so with carbaryl poisoning specifically. The goal of the present study was to evaluate the role of 2-PAM in a mouse model of lethal carbaryl poisoning. ... Female ICR Swiss Albino mice weighing 25-30 g were acclimated to the laboratory and housed in standard conditions. One hundred and ten mice received an LD50 dose of carbaryl subcutaneously. Ten minutes later, they were randomized by block randomization to one of eight treatment groups: normal saline control, atropine alone, 100 mg/kg 2-PAM with and without atropine, 50 mg/kg 2-PAM with and without atropine, and 25 mg/kg 2-PAM with and without atropine. All medications were given intraperitoneally and the atropine dose was constant at 4 mg/kg. The single objective endpoint was defined as survival to 24 hours. Fatalities were compared using a Chi squared or Fisher's exact test. ... Following an LD50 of carbaryl, 60% of the animals died. Atropine alone statistically improved survival (15% lethality). High dose 2-PAM with and without atropine was numerically worse, but not statistically different from control. While the middle dose of 2-PAM was no different than control, the addition of atropine improved survival (10% fatality). Low-dose 2-PAM statistically improved survival (25% lethality). Atropine further reduced lethality to 10%. ... When appropriately dosed, 2-PAM alone protects against carbaryl poisoning in mice. Failure to demonstrate this benefit in other models may be the result of oxime overdose.
The influence of cimetidine on the pharmacokinetic and pharmacodynamic response to the insecticide carbaryl has been investigated in isolated human erythrocytes (red blood cells; RBC) and after oral administration of 1 mg/kg carbaryl to four normal subjects in the absence or presence of cimetidine (300 mg, 8/hr for 3 days). Carbaryl induced a concentration-dependent reduction of isolated RBC acetylcholinesterase activity requiring 1 ug/mL to achieve 20% inhibition. Cimetidine also induced a dose-dependent inhibition of RBC acetylcholinesterase activity, but at 40-fold higher concentrations. At high concentrations, cimetidine was additive to carbaryl-induced inhibition of RBC acetylcholinesterase, but exhibited no effect at the therapeutically relevant concentrations (10 ug/mL). After oral carbaryl administration to normal subjects, plasma concentrations rapidly rose to a peak, then declined with a half-life of 0.79 +/- 0.47 hr. Oral carbaryl clearance was 5.4 +/- 2.0 L/min. Peak plasma carbaryl concentrations were associated with 27% inhibition of RBC acetylcholinesterase activity, and the concentration associated with a reduction of RBC acetylcholinesterase activity of 20% was 0.02 microgram/ml. The terminal half-life for the dynamic response was 2.6 +/- 1.5 hr. After pretreatment with cimetidine, peak plasma carbaryl concentrations doubled and clearance was reduced (to 2.5 +/- 1.5 L/min) (P<0.05). However, half-life remained unchanged. Despite increased carbaryl levels, the maximum inhibition of RBC acetylcholinesterase activity was significantly reduced, and the concentration of carbaryl required to achieve 20% inhibition of RBC acetylcholinesterase activity was increased to approximately 0.5 ug/mL. These results are consistent with the hypothesis that carbaryl is metabolized by drug-metabolizing enzymes that can be inhibited by cimetidine.
The administration of 2-pyridine aldoxime methyl chloride (2-PAM Cl) is a standard part of the regimen for treatment of human overexposure to many organophosphorus pesticides and nerve agents. However, some literature references indicate that poisoning by carbaryl (1-naphthyl N-methyl carbamate), an insecticide in everyday use, is aggravated by the administration of 2-PAM Cl. This effect has been reported in the mouse, rat, dog and man. ... The inhibition of both eel acetylcholinesterase (eel AChE, EC 3.1.1.7) and human serum cholinesterase (human BuChE, EC 3.1.1.8) by carbaryl was enhanced by several oximes. Based on 95% confidence limits the rank order of potentiation with eel AChE was TMB-4 = Toxogonin > HS-6 = HI-6 > 2-PAM Cl. By the same criterion, the rank order of potentiation with human BuChE was TMB-4 > Toxogonin > HS-6 = 2-PAM Cl. Carbaryl-challenged mice also reflected a potentiation since TMB-4 exacerbated the toxicity more than 2-PAM Cl. Our hypothesis is that certain oximes act as allosteric effectors of cholinesterases in carbaryl poisoning, resulting in enhanced inhibition rates and potentiation of carbaryl toxicity.
Antidiuretic agent diazoxide ... incr 20-fold toxicity of carbaryl in pig.
For more Interactions (Complete) data for CARBARYL (13 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 230 mg/kg
LD50 Rat skin 4000 mg/kg
LD50 Rat ip 64 mg/kg
LD50 Rat sc 1400 mg/kg
For more Non-Human Toxicity Values (Complete) data for CARBARYL (10 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.

Carbaryl can cause cancer according to The Environmental Protection Agency (EPA). It can cause developmental toxicity, female reproductive toxicity and male reproductive toxicity according to The National Institute for Occupational Safety and Health (NIOSH).
Carbaryl appears as a white crystalline solid. Insoluble in water. Combustible, although difficult to ignite. Toxic by inhalation (dust, etc.). Produces toxic oxides of nitrogen during combustion.
Carbaryl is a carbamate ester obtained by the formal condensation of 1-naphthol with methylcarbamic acid. It has a role as an EC 3.1.1.7 (acetylcholinesterase) inhibitor, a carbamate insecticide, an EC 3.1.1.8 (cholinesterase) inhibitor, an acaricide, an agrochemical and a plant growth retardant. It is a carbamate ester and a member of naphthalenes. It is functionally related to a methylcarbamic acid and a 1-naphthol.
Carbaryl is an insecticide used on a variety of crops. Acute (short-term) and chronic (long-term) occupational exposure of humans to carbaryl has been observed to cause cholinesterase inhibition, and reduced levels of this enzyme in the blood cause neurological effects. These effects appear to be reversible upon discontinuation of exposure. Headaches, memory loss, muscle weakness and cramps, and anorexia are caused by prolonged low-level exposure to carbaryl resulting from cholinesterase inhibition. EPA has classified carbaryl as a Group D, not classifiable as to human carcinogenicity.
Carbaril is a synthetic carbamate acetylcholinesterase inhibitor and suspected endocrine disruptor that is used as a pesticide. It is characterized as a toxic, white-grey odorless solid, and exposure occurs by inhalation, ingestion, or contact.
Carbaril is a carbamate pesticide. Carbamate pesticides are derived from carbamic acid and kill insects in a similar fashion as organophosphate insecticides. They are widely used in homes, gardens and agriculture. The first carbamate, carbaryl, was introduced in 1956 and more of it has been used throughout the world than all other carbamates combined. Because of carbaryl's relatively low mammalian oral and dermal toxicity and broad control spectrum, it has had wide use in lawn and garden settings. Most of the carbamates are extremely toxic to Hymenoptera, and precautions must be taken to avoid exposure to foraging bees or parasitic wasps. Some of the carbamates are translocated within plants, making them an effective systemic treatment. (L795)
A carbamate insecticide and parasiticide. It is a potent anticholinesterase agent belonging to the carbamate group of reversible cholinesterase inhibitors. It has a particularly low toxicity from dermal absorption and is used for control of head lice in some countries.

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Therapeutic Uses
Formulations of carbaryl have been used successfully to control human lice.
/VETERINARY ANIMALS/ To control fleas, lice, ticks, & mites on animals, poultry, & premises, incl sarcoptic mange on buffaloes; lice, ticks, & mange mites on cattle; fleas & resistant fleas on dogs; & fowl mites, lice, & fleas on poultry.
Medication (Vet): Ectoparasiticide

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.)