Absorption, Distribution and Excretion
In rats, absorption was rapid and complete (<48 hours) followed by excretion; enterohepatic circulation was significant. Bile metabolites were glucuronide; the main route of excretion was feces (primarily the original drug); a small amount was excreted in urine (primarily glucuronide). After 10 hours, the average skin absorption rate in rats was 20% (low-dose group). (Data from tables) This study determined the absorption, distribution, metabolism, and excretion of [Phenyl-UL-(14)C]KBR 2738 (pure benzamide) in male and female Wistar rats. Rats were administered a single oral dose of 1 mg/kg (low dose), a single oral dose of 100 mg/kg (high dose), and 15 repeated oral doses of 1 mg/kg/day (low dose). (14)C-KBR 2738 was rapidly absorbed from the gastrointestinal tract in all dose groups. Following single and repeated administration of low doses, peak plasma concentrations were reached within 5 to 10 minutes. Following high doses, peak plasma concentrations were detected 40 to 90 minutes post-administration. Bile duct cannulation experiments showed that the test compound was almost completely absorbed; 48 hours after duodenal administration, over 97% of the administered dose was absorbed by the gastrointestinal tract. These results indicate a significant first-pass effect and enterohepatic circulation. Tissue residues decreased rapidly; after 48 hours, the total residual radioactivity in all dose groups, except for the gastrointestinal tract, was less than 0.3% of the administered dose. The liver and kidneys were the organs with the highest radioactivity concentrations across all dose groups. No evidence of bioaccumulation was found. Radioactive material was excreted rapidly and almost completely, primarily via feces. Within 48 hours of administration, approximately 62–81% of the radioactive material was present in feces, and 15–36% in urine. Bile duct cannulation experiments showed that over 90% of the radioactive material was excreted via bile. Only 0.02% of the administered radioactive material was excreted in exhaled air. Following a single high-dose administration, the residual radioactivity in female rats (excluding the gastrointestinal tract) was significantly lower than that in male rats. After 15 repeated low-dose administrations, the renal excretion rate in female rats was significantly higher than that in male rats. Following a single low-dose administration, the renal excretion rate was significantly higher in both sexes than after a single high-dose administration. In a 56-day bioavailability study, KBR 2738 (95.4% purity) was added to the diet (containing 1% peanut oil excipient) of 10 SPF-grade Wistar rats (per sex per dose) for 56 days at dose levels of 0, 1000, 5000, 10000, 15000, or 20000 ppm (57.5, 284.7, 575.7, 943.8, and 1217.1 mg/kg/day for male rats, and 78.0, 407.1, 896.5, 1492.5, and 1896.7 mg/kg for female rats). The study aimed to determine whether intestinal absorption saturation occurred when KBR 2738 was added to the diet at concentrations ranging from 10,000 to 20,000 ppm. Therefore, KBR 2738 levels were measured in plasma and urine samples after a 3- or 4-week treatment period expected to reach steady state. Results showed that KBR 2738 levels in plasma samples from rats at the 20,000 ppm group were below the limit of detection. Urine samples showed measurable excretion of bound KBR 2738, indicating intestinal absorption within the studied dose range. Male rats showed the highest excretion rate at 15,000 ppm, indicating that intestinal absorption was saturated in the 15,000 to 20,000 ppm concentration range. At concentrations of 10,000 ppm and above, urinary excretion was slightly lower in female rats than in male rats. The highest value was measured at 20,000 ppm, indicating that intestinal absorption in female animals was not yet saturated at this dose level. Metabolites/Metabolites: In rats, the drug is rapidly absorbed and completely excreted (<48 hours); significant enterohepatic circulation is observed. The metabolite in bile is glucuronide; the main excretion route is feces (primarily the parent compound); a small amount is present in urine (primarily glucuronide). Metabolite characterization studies in rats showed that the main component detected in excrement was the unchanged parent compound, accounting for 62-75% of the dose, regardless of dosing regimen and sex. Metabolite 1, the glucuronide conjugate of the parent compound, accounted for 4% to 23% of the dose. Metabolite components 2 and 3 accounted for 3% and 7% of the dose, respectively. The presumed main biotransformation pathway is through the conjugation of aromatic hydroxyl groups to glucuronic acid. Before fecal excretion, hydrolysis in the intestine converts this conjugate back to the parent compound, thus entering the enterohepatic circulation. This indicates that although the main residue in feces is the unchanged parent compound, its absorption rate is close to 100% of the administered dose. Furthermore, hydroxylation occurs at positions 2, 3, and 4 of the cyclohexyl ring, subsequently forming glucuronic acid and sulfate conjugates of these hydroxylated metabolites. The identification rate of radioactive residues ranged from 88% to 99%, and was independent of dose and gender.

Toxicity Summary
Identification and Uses: Fenhexamid is a solid. Fenhexamid is a specific fungicide used to control Botrytis cinerea, Monilinia fructigena, Monilinia laxa, and Sclerotinia sclerotiorum. Human Exposure and Toxicity: In genetically engineered human breast cancer cells, benzylcarbamide exhibits endocrine-disrupting activity in androgen receptor reporter gene assays, demonstrating anti-androgenic effects. Fenhexamid increases miR-21 expression in MCF-7, T47D, and MDA-MB-231 human breast cancer cells and exhibits downstream anti-estrogenic activity. Animal Studies: Fenhexamid is slightly irritating when applied to rabbit skin, but causes minimal irritation when instilled into the rabbit eye. Skin sensitization tests in guinea pigs using the Bühler method were negative. A one-year chronic oral toxicity study in dogs showed that at the lowest observed adverse dose (LOAEL) of 124/133 mg/kg/day in male/female dogs, decreased red blood cell count, hemoglobin, and hematocrit, as well as an increase in Heinz bodies within red blood cells; furthermore, in female dogs, increases in absolute and relative adrenal weight were associated with histopathological findings of the incidence and severity of intracytoplasmic vacuolation in the adrenal cortex. In a developmental toxicity study, 16 female rabbits were administered 0, 100, 300, or 1000 mg/kg/day of benzylamidoamine via gavage from day 6 to day 18 of gestation. No treatment-related mortality, general appearance, or behavioral effects were observed. Under the conditions of this study, administration of the test compound at all tested doses did not induce any treatment-related fetal malformations or abnormalities. All effects on intrauterine development were associated with maternal toxicity; therefore, no primary developmental effects were observed. Benzocarbazin did not show teratogenicity at the upper limit of dose (up to 1000 mg/kg/day). Benzocarbazin was tested in the following assays: reverse gene mutation assay (Salmonella), no mutagenicity was shown regardless of metabolic activation; forward gene mutation assay (HGPRT locus), no mutagenicity was shown regardless of metabolic activation; micronucleus assay (mice), no mutagenicity was shown; unplanned DNA synthesis assay (rat hepatocytes), no mutagenicity was shown; chromosome aberration assay (CHO cells), no mutagenicity was shown regardless of metabolic activation. Ecotoxicity studies: Benzocarbazin showed moderate toxicity to rainbow trout and bluegill sunfish, and slight toxicity to scaly shrike. This study used a formulated benzylcarbazin (50% active ingredient) to conduct toxicity studies on beneficial insects. Based on mortality rates in predatory mites and rove beetles, the no-effect concentration (NOEC) was a formulated benzylcarbazin of 2 kg/ha. The NOEC for parasitic wasps was a formulated benzylcarbazin of 4 kg/ha.

---

Toxicity Data
LC50 (Rat)> 5,057 mg/m3/4h

---

Interactions
…This study investigated the effects of two fungicides, benzylamidophos and cyproconazole, alone and in combination, on two human cell lines (SH-SY5Y neurons and U-251 MG glial cells). After 48 hours of treatment with pesticides at escalating concentrations (1 to 1000 μM), gene expression profiles were examined in addition to detecting toxicity endpoints (including cell viability, mitochondrial depolarization, and intracellular glutathione levels). No significant differences were found between the two cell lines in terms of cell viability assessment or mitochondrial membrane potential when the pesticides were used alone or in combination. In contrast, SH-SY5Y cells showed significantly higher total thiol consumption than astrocytes in the presence of fungicides, indicating a higher sensitivity to oxidative stress. Treatment with both pesticides led to significant changes in the expression of genes regulating cell cycle control and growth (RB1, TIMP1), DNA loss response (ATM and CDA25A), and apoptosis control (FAS) in the cell lines. This study did not find that the combined use of benzyladenol and tebuconazole was significantly more toxic than the single treatment, but the changes in gene expression suggest that there may be differences in the sublethal response of the two cell lines to the single and combined treatments.

---

Non-human toxicity values
Rats oral LD50 >5000 mg/kg
Rats dermal LD50 >2000 mg/kg
Rats inhalation LC50 >5057 mg/m³/4 hr
Rats oral LD50 >2000 mg/kg /WDG increased by 50%/ /Taken from table/
Rats dermal LD50 >2000 mg/kg /WDG increased by 50%/ /Taken from table/

Fenhexamid is an aromatic amide formed by the condensation of the carboxyl group of 1-methylcyclohexanecarboxylic acid and the amino group of 4-amino-2,3-dichlorophenol. It is an EC 1.14.13.72 (methylsterol monooxygenase) inhibitor, sterol biosynthesis inhibitor, and antifungal pesticide. It is a monocarboxylic acid amide, belonging to the phenolic, aromatic amide, dichlorobenzene, and aniline fungicides. Fenhexamid is a locally absorbed systemic protective fungicide. It prevents fungal infection of plants by inhibiting spore germination and mycelial growth. This fungicide is absorbed by the waxy layer on the plant surface, thus preventing it from being washed away by rainwater or irrigation water. It is used to control gray mold on grapes, greenhouse tomatoes, ornamental plants, and berry crops (including blackberries, blueberries, currants, loganberries, raspberries, and strawberries); and brown rot on cherries, peaches, and nectarines.

---

Mechanism of Action
Fenhexamid is a newly developed insecticide for gray mold, and this paper demonstrates its ability to inhibit sterol biosynthesis.
When the fungus Botryotinia fuckeliana grows in the presence of benzylosporin, ergosterol levels decrease, and three 3-keto compounds (4α-methylcosanosterone, cosanosterone, and episterone) accumulate, indicating that benzylosporin inhibits 3-keto reductases involved in C-4 demethylation. Therefore, benzylosporin belongs to a novel and promising class of sterol biosynthesis inhibitors that have not previously been used in agriculture or medicine.

C14H17CL2NO2

302.1963

301.063

126833-17-8

213031

White powder
Solid

1.3±0.1 g/cm3

457.9±45.0 °C at 760 mmHg

153ºC

230.7±28.7 °C

0.0±1.2 mmHg at 25°C

1.604

4.02

2

2

2

19

331

0

ClC1C(=C(C([H])=C([H])C=1N([H])C(C1(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])=O)O[H])Cl

VDLGAVXLJYLFDH-UHFFFAOYSA-N

InChI=1S/C14H17Cl2NO2/c1-14(7-3-2-4-8-14)13(19)17-9-5-6-10(18)12(16)11(9)15/h5-6,18H,2-4,7-8H2,1H3,(H,17,19)

N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexane-1-carboxamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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 (~330.91 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (8.27 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (8.27 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.

---

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