When applied as a fungicide, captan may negatively disrupt microbial processes that are important for plant growth, making it ineffective [1].

Absorption, Distribution and Excretion
Captan and thiram are two widely used fungicides in agriculture, but biomonitoring data are mostly limited to measuring the concentration of captan metabolites in workers' urine samples, making the results difficult to interpret, such as internal dose estimation, daily variations based on job content, and the most likely exposure pathways. This study aimed to conduct repeated captan and thiram exposure biomeasurements in field workers to (i) better assess internal dose and primary exposure pathways based on job content, and (ii) establish the most appropriate sampling and analysis strategies. Detailed excretion time curves of captan and thiram-specific and non-specific biomarkers in urine were established for tree growers (n = 2) and grape growers (n = 3) over a typical work week (seven consecutive days), including spraying and harvesting activities. This study evaluated the impact of the expression of urine measurements, including creatinine-corrected or uncorrected excretion rates and cumulative amounts over specific time periods (8, 12, and 24 hours). Subsequently, using a kinetic model, the absorbed dose and primary route of entry were estimated based on 24-hour cumulative urine volume. Time-course analysis indicated that exposure levels were higher during spraying operations than during harvesting operations. Model simulations also showed that the subjects had limited absorption of the pesticide, with exposure primarily occurring through the skin. Furthermore, the study noted the advantage of using weight-corrected values from repeated 24-hour urine collections to express biomarker values compared to concentrations or excretion rates in random urine samples, without requiring creatinine correction. Numerous studies have shown that captan is readily absorbed from the gastrointestinal tract, rapidly metabolized, and excreted from the body. The possible metabolic pathways of tetrahydrophthalimide and the trichloromethylthio moiety have been elucidated. In rats, 92% of the tetrahydrophthalimide moiety was excreted within 48 hours and 97% within 96 hours (85% in urine and 12% in feces). Trichloromethyl sulfide is partially converted to phosgene, which is further metabolized to thiazolidin-2-thione-4-carboxylic acid, which is excreted in the urine of orally administered rats; carbon dioxide is also a product of phosgene metabolism, and its metabolic pathway involves the formation of carbonyl sulfide intermediates. Phosgene can also be detoxified by sulfites in the intestines and excreted in the urine of orally administered rats, generating dithiobis(methanesulfonic acid) and its disulfide monooxide derivatives.
Clotrimazole can be rapidly absorbed from the gastrointestinal tract and rapidly metabolized in the blood. It does not accumulate in tissues and readily reacts with thiol-containing compounds.
After oral administration (35)S-Clotrimazole, more than 90% of the radioactive material is excreted in feces and urine within 24 hours, and almost 100% is excreted within 3 days; 0.01-0.05% of the radioactive material is detected in organs or incorporated into proteins and nucleic acids.
For more data on the absorption, distribution and excretion (complete) of clodinazole (8 types in total), please visit the HSDB record page.

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Metabolism/Metabolites
Following oral exposure, captan fungicides are rapidly metabolized in the body, producing two metabolites detectable in urine: tetrahydrophthalimide (THPI) and thiazolidin-2-thion-4-carboxylic acid (TTCA). Both are considered effective biomarkers for occupational exposure.
Extensive studies on captan have shown that it is readily absorbed from the gastrointestinal tract and rapidly metabolized. It is excreted from the body after metabolism. The possible metabolic pathways of tetrahydrophthalimide and the trichloromethylthio moiety have been elucidated. In rats, 92% of the tetrahydrophthalimide moiety is excreted within 48 hours and 97% within 96 hours (85% in urine and 12% in feces). The trichloromethylthio moiety is converted to phosgene, which is further metabolized to thiazolidin-2-thion-4-carboxylic acid, excreted in the urine of orally administered rats; carbon dioxide is also a product of phosgene metabolism, its metabolic pathway involving the formation of carbonyl sulfide intermediates. Sulfogen phosgene can also be detoxified by sulfites in the intestine and excreted in the urine of orally administered rats, forming dithiobis(methanesulfonic acid) and its disulfide monooxide derivatives. Clotrimazole is metabolized in vitro via mixed hepatic metabolism. Oxidases oxidize clotrimazole to carbonyl sulfide, suggesting a metabolic pathway similar to that in vivo. Intestinal degradation appears to play a significant role in the metabolism of clotrimazole. The toxic metabolite sulfogen phosgene is generated from the trichloromethyl sulfide portion of the clotrimazole molecule in the presence of cellular thiols. Sulfogen phosgene is further metabolized to thiazolidin-2-thion-4-carboxylic acid, which is excreted in the urine of orally administered rats; carbon dioxide is also a product of sulfogen phosgene metabolism, with carbonyl sulfide as an intermediate (23% of radioactive carbon is excreted as CO2). Sulfogen phosgene can also be detoxified by sulfites in the intestine and excreted in the urine of orally administered rats, forming dithiobis(methanesulfonic acid) and its disulfide monooxide derivatives.
For more complete data on captan metabolism/metabolites (9 in total), please visit the HSDB record page.

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Biological half-life
The skin permeability of (14)C-labeled captan was studied in juvenile and adult rats…. Skin absorption was biphasic, with at least 93% of the dose having a half-life of at least 1000 hours on the skin.
The degradation of captan (79.9% purity) during incubation with human blood was investigated. Captan at a concentration of approximately 1 μg/mL was mixed with blood at 37 °C. The reaction was terminated by the addition of phosphoric acid and acetone at different time points from 0 to 31 seconds. The degradation of captan and the formation of THPI were measured. Captan was rapidly metabolized to THPI. The calculated half-life was 0.97 seconds. Mass spectrometry analysis showed that THPI was the only degradation product.
...The half-life of captan is very short, and the concentrations of phosgene in the blood (0.9 seconds and 0.6 seconds, respectively) indicate that these compounds do not directly reach the fetus after oral ingestion, but THPI may.

[1]. Effects of the fungicide Captan on some functional groups of soil microflora. Applied Soil Ecology Volume 7, Issue 3, March 1998, Pages 245-255.

According to the U.S. Environmental Protection Agency (EPA), captan may be carcinogenic. Captan is a white solid soluble in a liquid carrier and belongs to the water-emulsifier class. It can cause illness through inhalation, skin absorption, and/or ingestion. The main hazard of this substance lies in its environmental threat. In the event of a leak, immediate measures should be taken to limit its spread into the environment. Because it is a liquid, it can easily seep into the soil and contaminate groundwater. It is used as a fungicide. Captan is a dicarboxyimide with the chemical formula 3a,4,7,7a-tetrahydrophthalimide, in which the hydrogen atom bonded to the nitrogen atom is replaced by a trichloromethyl group. It is a non-systemic fungicide introduced in the 1950s and widely used to control fungal diseases in fruits, vegetables, and ornamental crops. It is an antifungal pesticide. It belongs to the isoindole, organochlorine, organosulfur, and phthalimide class of fungicides. Captan is a fungicide used for fruits, vegetables, and ornamental plants. Acute (short-term) skin contact with captan may cause dermatitis and conjunctivitis in humans. Ingestion of large amounts of captan may cause vomiting and diarrhea in humans. Studies have found that captan is carcinogenic to certain strains of mice, which developed duodenal tumors after ingesting captan through diet. However, no increased tumor incidence was observed in mice exposed to captan via gavage (experimental administration of the chemical into the stomach) or injection. The U.S. Environmental Protection Agency (EPA) has classified captan as a Group 2 carcinogen, meaning it is a possible human carcinogen. Captan is a general-purpose pesticide (GUP) belonging to the phthalimide class of fungicides. While it can be used alone, captan is often added as an ingredient in mixtures of other pesticides. It is used to control diseases in a variety of fruits, vegetables, and ornamental plants. It can also improve the appearance of many fruits, making them look more vibrant and healthy. Long-term, high-dose use of captan is believed to be carcinogenic, causing cytotoxicity and regenerative cell proliferation. However, these high doses of captan are far higher than what people might ingest in their daily diet, and also higher than what they might be exposed to in their occupational or residential environments. Therefore, captan is unlikely to be a human carcinogen and does not pose a worrying cancer risk.
One of the phthalimide fungicides.

C9H8CL3NO2S

300.58

298.934

133-06-2

Captan-d6;1330190-00-5

8606

White to cream powder
Crystals from carbon tetrachloride
Colorless crystals
White, crystalline powder [Note: Commercial product is a yellow powder]

1.6±0.1 g/cm3

314.2±52.0 °C at 760 mmHg

178°C

143.8±30.7 °C

0.0±0.7 mmHg at 25°C

1.636

1.85

0

3

1

16

340

0

C1=CCC2C(C1)C(=O)N(C2=O)SC(Cl)(Cl)Cl

LDVVMCZRFWMZSG-UHFFFAOYSA-N

InChI=1S/C9H8Cl3NO2S/c10-9(11,12)16-13-7(14)5-3-1-2-4-6(5)8(13)15/h1-2,5-6H,3-4H2

2-(trichloromethylsulfanyl)-3a,4,7,7a-tetrahydroisoindole-1,3-dione

AI3-26538 Buvisild K Glyodex 3722Captan HexacapCaptabAmercideAacaptan Agrosol S Bangton Captadin Captaf Captax Vanicide

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 : ~50 mg/mL (~166.34 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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