Absorption, Distribution and Excretion
... Seven male rats were used /in a metabolic study/; one received only non-labeled propoxur; the others received 1 mg/kg (14)C-labeled (ring) with sacrifice at 1, 4, 8, 24, 48, and 72 hr. The rats were sagittally sectioned and exposed (29-124 days) in direct contact with X-ray film. At 1 hour, radioactivity was detectable in all organs (particularly intestines) except the bone. After 24 hr, there were high concentrations of radioactivity in the gastrointestinal tract and bladder, as well as the mucous membranes of the pharyngeal region. At 48 and 72 hr, some radioactivity was still detectable in the liver, kidneys and mucous membranes of the pharyngeal system. Propoxur (and/or its metabolites) was shown to be distributed via the lymph system.
Two studies ... provide information on the dermal adsorption of propoxur in humans and rats. In the human study, six individuals received a single intravenous dose of (14)C-propoxur, 1 Ci/mL. Total urine was collected for five days post-dose and the percent of radiolabeled-dose excreted in the urine was determined. Subsequently the same six individuals received a single dermal dose of (14)C-propoxur at 4 ug/sq cm for an exposure period of 24 hr. Total urine was collected for five days post-dose and the percent of radiolabeled-dose excreted in the urine was determined. The radiolabel excreted was corrected for the 81.8% of label excreted following the iv dose. Corrected total excretion was 19.6 percent of the dermally administered dose. In the rat study, four doses (0.648, 6.91, 69.5, and 692 ug/sq cm) were administered /to rats (strain and sex not given)/ for durations of 0.5, 1, 2, 4, 8, and 24 hr. Test material was administered in ethanol, a solvent which can increase the absorption of a dissolved chemical. Since percent absorption decreases in a nonlinear manner with dose, the absorption from the dose of 6.91 ug/sq cm (the nearest dose to that administered in the human study) was selected for comparison with the human study. The results indicate (for durations 0.5, 1, 2, 4, 8, and 32 hr) a total of 7.88, 10.2, 17.9, 23.2, and 32.5% absorption, respectively. The percent absorbed in the rat study exceeds the percent absorbed in the human study for exposure durations of 8 and 24 hr. This is expected, even without the addition of ethanol, as rat skin is more permeable than human skin. Alternatively, the use of acetone in the human study would show an expected increase of propoxur penetration.
In a dermal absorption study with rats, a mixture of 50% ethanol and 50% water was used as a solvent, with doses of 0.648, 6.91, 69.5, or 692 ug/sq cm (corresponding nominal doses: 0.009875, 0.105, 1.0625, and 10.5 mg, respectively) radiolabeled propoxur. The highest values for absorption (50 to 64.9%) were observed with the two lowest dose levels, with the highest percentages of radioactivity (0.1-0.18%) in the blood occurring at these dose levels at 0.5 to 1.0 hr after dosage. Because propoxur was applied in a mixture of ethanol and water, the values obtained for dermal absorption were probably somewhat higher than if water alone had been the solvent.
Like houseflies, rat ... degrades arpocarb... with 30% of applied dose expired as CO2 within 48-hr...
For more Absorption, Distribution and Excretion (Complete) data for Propoxur (15 total), please visit the HSDB record page.

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Metabolism / Metabolites
In a metabolism study, the following metabolites were identified in the urine of rats which had been fed 8000 ppm propoxur for 13 weeks: M1 = 1,2-dihydoxybenzene (= catechol); M2 = 2-isopropoxyphenol; M3 = 2-hydroxyphenyl methylcarbamate; M4 = 2- isopropoxyphenylcarbamic acid; M5 = isopropoxyphenyl-hydroxy(-) methylcarbamate; M6 = 2-isopropoxy-5-hydroxyphenyl-methylcarbamate; M7 = 2-isopropoxy-5-hydroxyphenyl carbamic acid; M8 = 2-isopropoxy-5-hydroxyphenylhydroxymethyl carbamate; M9 = 1,5-dihydroxy-2-isopropoxybenzene. In additional studies, M6 (= 2-isopropoxy-5-hydroxyphenylmethylcarbamate) was identified as a principle metabolite in hamsters, mice, and humans. The nitrosated compound M9A ( = 1-hydroxy-2- isopropoxy-4-nitrobenzene) has been identified as a metabolite in rats and mice, the rhesus monkey, and humans. Evidence from the human study suggests that M9A is synthesized in the stomach.
Groups of 5 female rats received 50, 250, or 500 ppm unlabeled propoxur in their diets for 5 months, then received (by oral gavage) a single dose of 1 mg/kg radiolabelled material. Urine samples taken in the period from 0 to 24 hr after dosage had 87.9 to 99.8% of the total radiolabel; by thin layer chromatography it was found that 97-98% of the activity remained at the origin, and was contained in conjugated metabolites and/or extremely polar metabolites of unknown structure. By enzymatic cleavage 80-86% of the activity was identified as specific metabolites including M1, M2, M3, M4, M5, M6, M7, M8, as well as M6CII (= 2-isopropoxy-5-hydroxyphenyl carbamic acid), MS3 (= 2-isopropoxy-5-hydroxyphenyl-hydroxymethyl carbamate, and M7A (= 2- isopropoxy-3-hydroxyphenyl-methyl carbamate).
In ... studies with ... Musca domestica l ... /metabolites were/ (in order of decr amt): 5-hydroxy-2-isopropoxyphenyl methylcarbamate, 2-hydroxyphenyl methylcarbamate & acetone, 2-isopropoxyphenyl n-hydroxymethylcarbamate, & 2-isopropoxyphenyl carbamate. There were 6 or more addnl unidentified cmpd.
When the tert-carbon of 2-isopropoxy group of propoxur is oxidized to form a hemiketal, mono-N-methylcarbamoylcatechol is produced as a hydrolyzed metabolite that can normally be detected as 2-isopropoxyphenol by hydrolysis of the carbamoyl ester linkage, although this phenol has still not been detected. The 5-position of the phenyl ring is selectively metabolized in insects and their microsomes.
For more Metabolism/Metabolites (Complete) data for Propoxur (7 total), please visit the HSDB record page.
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
Following a single oral dose in rats, peak circulating & tissue concn of the major metabolite, isopropoxyl phenol, were achieved at 30 to 60 minutes, & the parent propoxur is eliminated very quickly (half-life = 11-15 min).

Toxicity Summary
Propoxur 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
LC50 (rat) = 1,440 mg/m3/1h

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Interactions
... The effects of subchronic per os exposures to cadmium chloride (CdCl(2)) and ... propoxur (Pr), were investigated in male Wistar rats on general toxicological (body weight gain, relative organ weights) hematological (RBC, WBC, Ht, MCV, cell content of the femoral bone marrow) immune function (plaque forming cell (PFC) assay, delayed type hypersensitivity (DTH) reaction) and neurotoxicological (spontaneous and stimulus-evoked cortical activity, nerve conduction velocity) parameters. The animals were treated for 4, 8 and 12 weeks with 6.43 mg/kg CdCl(2), 8.51 mg/kg Pr, or with a combination of 6.43 mg/kg CdCl(2)+0.851 mg/kg Pr or 8.51 mg/kg Pr+1.61 mg/kg CdCl(2). Cadmium exposure affected the relative thymus, liver, and adrenal weight, RBC count, hematocrit and MCV, and there was an increase in nerve conduction velocity and a decrease in the cortical evoked potential latency. Pr induced a decrease in thymus weight, had some effect on the liver weight but none on the electrophysiological parameters. A significant interaction between Cd and Pr was detected by the following parameters: RBC, Ht, PFC, and nerve conduction velocity ...
The toxicity of ... propoxur decreased in rats given Aroclor 1242.
... The effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immunomodulatory properties, was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg bw) in olive oil, group III received a combination of propoxur (10 mg/kg bw) and W. somnifera (100 mg/kg bw) suspension, and group IV W. somnifera (100 mg/kg bw) only. All animals were treated for 30 days. Cognitive behavior was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg bw) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur.
The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur -induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur ... orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leukocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values ...
For more Interactions (Complete) data for Propoxur (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat acute oral 95 to 104 mg/kg
LD50 Rat (male) oral 83 mg/kg
LD50 Rat (female) oral 86 mg/kg
LD50 Rat ip 30 mg/kg
For more Non-Human Toxicity Values (Complete) data for Propoxur (15 total), please visit the HSDB record page.

Propoxur can cause cancer according to The Environmental Protection Agency (EPA).
Propoxur is a white to tan crystalline powder with a faint, characteristic odor. Used as an insecticide. (NIOSH, 2024)
Propoxur is a carbamate ester that is phenyl methylcarbamate substituted at position 2 by a propan-2-yloxy group. It has a role as an EC 3.1.1.7 (acetylcholinesterase) inhibitor, a carbamate insecticide, an acaricide and an agrochemical. It is a carbamate ester and an aromatic ether. It is functionally related to a methylcarbamic acid and a 2-isopropoxyphenol.
Propoxur is an insecticide used to control cockroaches, flies, mosquitoes, and lawn and turf insects. Acute (short-term) exposure of humans to propoxur by ingestion leads to cholinesterase inhibition of red blood cells, with mild cholinergic symptoms including blurred vision, nausea, vomiting, sweating, and tachycardia; however, the effects are transient. Chronic (long-term) inhalation exposure has resulted in depressed cholinesterase levels, headaches, vomiting, and nausea in humans. Chronic ingestion studies in animals have reported depressed cholinesterase levels, depressed body weight, effects to the liver and bladder, and a slight increase in neuropathy. No information is available on the reproductive, developmental, or carcinogenic effects of propoxur in humans. Mixed results are available from cancer studies of propoxur in animals. EPA has not classified propoxur for carcinogenicity.
Propoxur is a synthetic carbamate, aromatic ether compound, and acetylcholinesterase inhibitor that is used as a pesticide. It is characterized as a toxic, white to tan crystalline solid with a faint odor, and exposure occurs by inhalation, ingestion, or contact.
Propoxur 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.

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Mechanism of Action
/A/ review of studies /was undertaken/ to evaluate mechanisms of rat urinary bladder tumors ... Propoxur or a metabolite was postulated to operate on or with growth factors to elicit hyperplasia and eventual tumor development. Since some propoxur metabolites are phenols, and since some phenols share with propoxur the property of being urinary bladder oncogens only at extremely high dose levels, threshold effects may be present. Low urinary pH was noted to inhibit binding of epidermal growth factor, which is abundant in rat urine. This is consistent with rat studies, in which pH reduction markedly reduced the extent of hyperplasia. Perspectives offered in this discussion suggest that propoxur-induced tumors in rats may not be relevant to man, but the "possible adverse effect" designation remains until more definitive evidence can be obtained.
Carbamylation of acetylcholinesterase produces accumulation of acetylcholine and the picture of muscarinic and nicotinic poisoning. Spontaneous hydrolysis of the carbamate-cholinesterase complex occurs in vivo, leading to the disappearance of clinical effects within 24 hours. Penetration of the blood-brain barrier by the carbamates is insignificant; for this reason, few CNS symptoms occur.
Propoxur inhibits cholinesterase & this effect is apparently the basis of its toxic action.

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Therapeutic Uses
Medication (Vet): Effective against fleas and ticks on cattle, horse, cats, and dogs ... and sarcoptic mange of cattle ... Protection against ticks appears to wane after 1 week.

C11H15NO3

209.25

209.105

114-26-1

Propoxur-d3;1219798-56-7

4944

Minute crystals
White, crystalline powder
White to tan, crystalline solid

1.1±0.1 g/cm3

327.2±44.0 °C at 760 mmHg

91°C

151.7±28.4 °C

0.0±0.7 mmHg at 25°C

1.499

2.56

1

3

4

15

206

0

CC(C)OC1=CC=CC=C1OC(NC)=O

ISRUGXGCCGIOQO-UHFFFAOYSA-N

InChI=1S/C11H15NO3/c1-8(2)14-9-6-4-5-7-10(9)15-11(13)12-3/h4-8H,1-3H3,(H,12,13)

(2-propan-2-yloxyphenyl) N-methylcarbamate

AI3-25671; Baygon; Propoxur

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 (~477.92 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (9.94 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 20.8 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: ≥ 2.08 mg/mL (9.94 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), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (9.94 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 20.8 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.)