Absorption, Distribution and Excretion
This metabolic study used seven male rats; one received only unlabeled propoxyurea; the remaining rats received 1 mg/kg of 14C-labeled (cyclic) propoxyurea and were sacrificed at 1, 4, 8, 24, 48, and 72 hours. The rats were sectioned sagittally and exposed to X-ray film (29–124 days). One hour later, radioactivity was detectable in all organs except bones (especially the intestines). After 24 hours, high concentrations of radioactivity were observed in the gastrointestinal tract, bladder, and pharyngeal mucosa. After 48 and 72 hours, some radioactivity was still detectable in the liver, kidneys, and pharyngeal mucosa. Propoxyurea (and its metabolites) has been shown to be distributed via the lymphatic system. Two studies… provided information on the absorption of propoxyurea through the skin in humans and rats. In the human study, six subjects received a single intravenous injection of 1 Ci/mL of 14C-propoxyurea. All urine samples were collected within five days of administration, and the percentage of the radiolabeled dose in the urine was determined. Subsequently, the six subjects received a single dermal injection of 14C-propoxyurea at a dose of 4 μg/cm², with an exposure time of 24 hours. All urine samples were collected within five days of administration, and the percentage of the radiolabeled dose in the urine was determined. The excretion rate of the radiolabeled dose after dermal administration was corrected for 81.8% after intravenous administration. The corrected total excretion was 19.6% of the dermal dose. In rat studies, four doses (0.648, 6.91, 69.5, and 692 μg/cm²) were administered to rats (strain and sex not specified) at times of 0.5, 1, 2, 4, 8, and 24 hours. The test substance was dissolved in ethanol, a solvent that can enhance the absorption of dissolved chemicals. Because absorption decreases non-linearly with dose, the absorption rate at a dose of 6.91 μg/cm² (closest to the dose used in human studies) was chosen for comparison with human study results. The results showed that (dose administration times of 0.5, 1, 2, 4, 8, and 32 hours) the total absorption rates were 7.88%, 10.2%, 17.9%, 23.2%, and 32.5%, respectively. In rat studies, the percentage of absorption was higher at both 8 and 24 hours of exposure than in human studies. This is expected even without the addition of ethanol, as rat skin is more permeable than human skin. Alternatively, the use of acetone in human studies would have shown the expected increase in propoxyurea permeability. In a rat skin absorption study, radiolabeled propoxyurea was administered at doses of 0.648, 6.91, 69.5, or 692 μg/cm² (corresponding nominal doses of 0.009875, 0.105, 1.0625, and 10.5 mg) using a mixture of 50% ethanol and 50% water as a solvent. The highest absorption values (50% to 64.9%) were observed at the two lowest dose levels, with the highest percentage of radioactivity in the blood (0.1% to 0.18%) occurring 0.5 to 1.0 hours after administration. Because propoxyurea was administered in a mixture of ethanol and water, the measured skin absorption values may be slightly higher than when water was used as the solvent alone. Like houseflies, rats…degrade aprokab…30% of the administered dose is excreted as carbon dioxide within 48 hours… For more complete data on the absorption, distribution, and excretion of propoxyurea (15 types), please visit the HSDB records page.

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Metabolism/Metabolites
In a metabolic study, the following metabolites were identified in the urine of rats fed 8000 ppm propoxyurea for 13 weeks: M1 = 1,2-dihydroxybenzene (=catechol); M2 = 2-isopropoxyphenol; M3 = 2-hydroxyphenylmethylcarbamate; M4 = 2-isopropoxyphenylcarbamic acid; M5 = isopropoxyphenyl-hydroxy(-)methylcarbamate; M6 = 2-isopropoxy-5-hydroxyphenylmethylcarbamate; M7 = 2-isopropoxy-5-hydroxyphenylcarbamic acid; M8 = 2-isopropoxy-5-hydroxyphenylhydroxymethylcarbamate; M9 = 1,5-dihydroxy-2-isopropoxybenzene. In other studies, M6 (= 2-isopropoxy-5-hydroxyphenylmethylcarbamate) has been identified as a major metabolite in hamsters, mice, and humans.
The nitrosamine M9A (= 1-hydroxy-2-isopropoxy-4-nitrobenzene) has been identified as a metabolite in rats, mice, rhesus monkeys, and humans. Human studies suggest that M9A is synthesized in the stomach. Five female rats were randomly divided into three groups and fed diets containing 50, 250, or 500 ppm of unlabeled propoxyurea for five months, respectively. They were then administered a single dose of 1 mg/kg of the radiolabeled substance via gavage. In urine samples collected 0 to 24 hours after administration, the radiolabeled substance comprised 87.9% to 99.8% of the total amount. Thin-layer chromatography analysis revealed that 97% to 98% of the radioactivity remained in situ, present in bound metabolites and/or extremely polar metabolites of unknown structure. Enzymatic hydrolysis revealed 80-86% of the activity as specific metabolites, including M1, M2, M3, M4, M5, M6, M7, M8, as well as M6CII (= 2-isopropoxy-5-hydroxyphenylcarbamate), MS3 (= 2-isopropoxy-5-hydroxyphenyl hydroxymethylcarbamate), and M7A (= 2-isopropoxy-3-hydroxyphenyl methylcarbamate). In studies of… houseflies (Musca domestica)… the metabolites (in descending order of abundance) were: 5-hydroxy-2-isopropoxyphenyl methylcarbamate, 2-hydroxyphenyl methylcarbamate and acetone, 2-isopropoxyphenyl n-hydroxymethylcarbamate and 2-isopropoxyphenyl carbamate. Six or more unidentified compounds were also found.
When the tertiary carbon atom of the 2-isopropoxy group...propoxyurea is oxidized to a hemiketal, the hydrolysis metabolite being mono-N-methylcarbamoylcatechol, which can usually be hydrolyzed via carbamoyl ester bonds to generate 2-isopropoxyphenol, but this phenol has not yet been detected. The 5-position of the benzene ring is selectively metabolized in insects and their microsomes.
For more complete data on the metabolism/metabolites of propoxyurea (7 metabolites in total), please visit the HSDB record page.
Carbamates are enzymatically hydrolyzed in the liver; degradation products are excreted via the kidneys and liver. (L793)

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Biological half-life
After a single oral administration in rats, the peak circulating and tissue concentrations of the major metabolite isopropoxyphenol are reached between 30 and 60 minutes. The half-life of the parent propoxyurea is very rapid (half-life = 11-15 minutes).

Toxicity Summary
Propoxyurea is a cholinesterase, or acetylcholinesterase (AChE) inhibitor. Carbamate compounds form unstable complexes with cholinesterase by carbamylation of the enzyme's active site. This inhibition is reversible. Cholinesterase inhibitors suppress 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-dose exposure typically results in 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 uninterrupted muscle contraction.

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

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Interactions
……This study investigated the effects of subchronic oral exposure to cadmium chloride (CdCl(2)) and propoxyurea (Pr) on general toxicology (weight gain, relative organ weight), hematology (erythrocytes, leukocytes, hematocrit, mean erythrocyte volume, femoral bone marrow cell content), immune function (plaque-forming cell (PFC) assay, delayed-type hypersensitivity (DTH)) and neurotoxicology (spontaneous and stimulus-induced cortical activity, nerve conduction velocity) parameters in male Wistar rats. Animals were treated with 6.43 mg/kg CdCl₂, 8.51 mg/kg Pr, or a combination of 6.43 mg/kg CdCl₂ + 0.851 mg/kg Pr, or 8.51 mg/kg Pr + 1.61 mg/kg CdCl₂ for 4, 8, and 12 weeks, respectively. Cadmium exposure affected the relative weights of the thymus, liver, and adrenal glands, red blood cell count, hematocrit, and mean corpuscular volume (MCV), and led to increased nerve conduction velocity and shortened latency of cortical evoked potentials. Pr caused a decrease in thymus weight and had some effect on liver weight, but had no effect on electrophysiological parameters. Significant interactions between cadmium (Cd) and pyrimethamine (Pr) were detected using the following parameters: red blood cell count (RBC), hematocrit (Ht), prefrontal cortex (PFC), and nerve conduction velocity…
Practicing Aroclor 1242 reduced the toxicity of pyrimethamine in rats.
…This study investigated the effects of ashwagandha (Withania somnifera), a commonly used herb with anti-stress and immunomodulatory properties, on pyrimethamine-induced acetylcholinesterase inhibition and cognitive impairment in rats. Male Wistar rats were divided into four groups. Group 1 was treated with olive oil as a control. Group 2 was orally administered pyrimethamine (10 mg/kg body weight) in olive oil solution. Group 3 was orally administered a suspension of pyrimethamine (10 mg/kg body weight) and ashwagandha (100 mg/kg body weight). Group 4 was orally administered ashwagandha (100 mg/kg body weight) only. All animals received treatment for 30 days. Cognitive behavior was assessed using the elevated cruciate maze transfer latency method. Acetylcholinesterase (AChE) activity in blood and brain tissue was also measured. Oral administration of propoxyurea (10 mg/kg body weight) significantly reduced AChE activity in brain tissue and blood. The acquisition and maintenance transfer latency were significantly prolonged in rats treated with propoxyurea. Oral administration of W. somnifera had a protective effect, alleviating AChE suppression and cognitive impairment induced by subchronic propoxyurea exposure. This study investigated the attenuating effect of melatonin, a major secretion of the pineal gland, on propoxyurea-induced cell-mediated immune (CMI) responses. Male Wistar albino rats were orally administered propoxyurea (10 mg/kg) and/or melatonin (10 mg/kg) for 4 weeks. Cell-mediated immunity (CMI) was assessed by measuring delayed-type hypersensitivity (DTH), leukocyte and macrophage migration inhibition (LMI and MMI) responses, and levels of cytokines TNF-α and IFN-γ. Rats exposed to propoxyurea for 4 weeks showed significantly reduced DTH, LMI, and MMI responses. Propoxyurea also significantly inhibited the production of TNF-α and IFN-γ. Administration of melatonin alone significantly enhanced the DTH response. Although LMI and MMI responses remained unchanged, cytokine levels were significantly elevated compared to the control group. Co-administration of melatonin with propoxyurea significantly eliminated the pesticide's effects on cell-mediated immune responses (CMI), except for delayed-type hypersensitivity (DTH), and cytokine levels returned to near-control/normal values…
For more complete data on propoxyurea interactions (6 items in total), please visit the HSDB record page.

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Non-human toxicity values
Acute oral LD50 in rats: 95 to 104 mg/kg
Oral LD50 in male rats: 83 mg/kg
Oral LD50 in female rats: 86 mg/kg
Intraperitoneal LD50 in rats: 30 mg/kg
For more complete data on non-human toxicity values of propoxyurea (15 values in total), please visit the HSDB record page.

According to the U.S. Environmental Protection Agency (EPA), propoxyurea may be carcinogenic. Propoxyurea is a white to brownish-yellow crystalline powder with a faint, characteristic odor. It is used as an insecticide. (NIOSH, 2024) Propoxyurea is a carbamate, a compound in which phenyl methyl carbamate is substituted at the 2-position with propion-2-oxy group. It is an EC 3.1.1.7 (acetylcholinesterase) inhibitor, carbamate insecticide, acaricide, and agrochemical. It is a carbamate and aromatic ether. Its structure is related to methylcarbamate and 2-isopropoxyphenol. Propoxyurea is an insecticide used to control cockroaches, flies, mosquitoes, and lawn and turf pests. Short-term ingestion of propoxyurea in humans can lead to inhibition of erythrocyte cholinesterase, resulting in mild cholinergic symptoms, including blurred vision, nausea, vomiting, sweating, and tachycardia; however, these effects are transient. Long-term inhalation of propoxyurea can lead to decreased cholinesterase levels, headache, vomiting, and nausea in humans. Studies of long-term propoxyurea intake in animals have shown decreased cholinesterase levels, weight loss, liver and bladder damage, and a slight increase in neuropathy. Currently, there is no information on the effects of propoxyurea on human reproduction, development, or carcinogenicity. Animal studies on the carcinogenicity of propoxyurea have yielded mixed results. The U.S. Environmental Protection Agency has not classified propoxyurea as a carcinogen. Propoxyurea is a synthetic carbamate aromatic ether compound and an acetylcholinesterase inhibitor used as an insecticide. Prothiocarbofuran is a toxic white to brownish-red crystalline solid with a slight odor, which can be acquired through inhalation, ingestion, or contact. Prothiocarbofuran is a carbamate insecticide. Carbamate insecticides are derived from carbamic acid, and their insecticidal mechanism is similar to that of organophosphate insecticides. They are widely used in homes, gardens, and agriculture. The first carbamate insecticide, Sevin, was introduced in 1956, and its global usage exceeds the combined usage of all other carbamate insecticides. 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 hymenopteran insects, requiring precautions to prevent contact with insects such as bees or parasitic wasps. Some carbamate insecticides can be transported within plants, making them effective systemic treatments. (L795)
A carbamate insecticide.

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Mechanism of Action
A review study aimed to assess the mechanism of action of propoxyurea or its metabolites in rat bladder tumors…it is hypothesized that propoxyurea or its metabolites induce proliferation and ultimately lead to tumorigenesis by acting on or synergistically with growth factors. Since some propoxyurea metabolites are phenolic compounds, and some phenolic compounds, like propoxyurea, are only carcinogenic to the bladder at very high doses, a threshold effect may exist. The study found that low urine pH inhibited the binding of epidermal growth factor (which is abundant in rat urine). This is consistent with findings in rat studies that lowering urine pH significantly reduces the degree of proliferation. The points raised in this discussion suggest that the tumors induced by propoxyurea in rats may be unrelated to humans, but are still classified as a "possible adverse reaction" pending more conclusive evidence. Carbamate carbamate enzyme carbamate leads to acetylcholine accumulation and symptoms of muscarinic and nicotinic poisoning. The carbamate-cholinesterase complex undergoes spontaneous hydrolysis in vivo, resulting in the disappearance of clinical symptoms within 24 hours. Carbamates have a weak ability to cross the blood-brain barrier; therefore, central nervous system symptoms are rare. Propoxyurea inhibits cholinesterase, an effect that is clearly the basis of its toxicity.
Therapeutic Uses
Veterinary: Effective against fleas and ticks on cattle, horses, cats, and dogs…and against mange in cattle…Protective effect against ticks appears to diminish after one 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.)