Absorption, Distribution and Excretion
Data on the dermal absorption of benzyl benzoate are currently unavailable. Some early studies have indicated some dermal absorption, but the amount absorbed has not been quantified. This study evaluated the maternal and fetal toxicity of benzyl benzoate (a commonly used antiparasitic insecticide) in pregnant rats at daily oral doses of 25 and 100 mg/kg. Biochemical, histopathological, and morphological examinations were performed. Maternal weight, food and water consumption were observed, and cesarean sections were performed on day 20 of gestation (GD 20). Histopathological examination of the liver, kidneys, heart, brain, and placenta of both maternal and fetal rats was conducted under an optical microscope. Immunohistochemical staining for vascular endothelial growth factor (VEGF) was performed on the liver and placenta of both maternal and fetal rats. Morphometric analysis was performed on fetal body length, placental measurements, and fetal skeletal staining. Statistically significant changes were observed in biochemical parameters, placental measurements, and skeletal measurements in the treatment group. In addition to histopathological changes, significant differences in VEGF immunolocalization were also observed in the treatment group. These results indicate that benzyl benzoate and its metabolites can be transported to the placenta and ultimately enter the fetus. In in vivo studies in humans and monkeys, the percutaneous absorption of benzyl benzoate was measured. With the administration site closed, 54% of the administered dose permeated into the human skin within 24 hours, while the absorption rate through the monkey skin was 69%. Metabolites/Metabolites: Rapidly hydrolyzed to benzoic acid and benzyl alcohol, with benzyl alcohol further oxidized to benzoic acid. Benzoic acid combines with glycine to form hippuric acid. It is then converted to hippuric acid in vivo.

Toxicity Summary
Identification and Uses: Benzyl benzoate is a liquid. It is used as a solvent for cellulose acetate, nitrocellulose, and artificial musk; as a substitute for camphor in celluloid and plastic nitrocellulose compounds; as a fragrance fixative; and as a flavoring agent in candies and chewing gum. As an insecticide/acaricide, it has been used to control dust mites on carpets, mattresses, upholstery, and furniture. Benzyl benzoate is used as an alternative for topical treatment of scabies and has also been used topically for lice infestation. It is used in veterinary medicine as an acaricide and liceicide, but is contraindicated in cats. It was used in the Vietnam War to eradicate and repel certain ticks and mites. Human Studies: Direct contact may cause skin irritation. Direct contact with the liquid is irritating to the eyes, but no injuries have been reported. Topical application of benzyl benzoate emulsion has not been shown to have adverse effects on pregnancy outcomes. Benzyl benzoate has shown an estrogen-like response in cultured human breast cancer cell lines in vitro. Animal studies: A 13-week rat study showed that a daily dose of 800 mg/kg resulted in reduced body weight gain and increased mortality. Neurotoxicity symptoms, such as unsteady gait, dyspnea, and somnolence, were observed. Periorbital hemorrhage was observed, and histological lesions were found in the brain, thymus, skeletal muscle, and kidneys. Benzyl benzoate was not tested for carcinogenicity, but its metabolite benzyl alcohol was tested in rats and mice. Benzyl alcohol was not found to be carcinogenic. In pregnant rats, the maternal and fetal toxicity of benzyl benzoate was assessed by daily oral administration of 25 and 100 mg/kg doses. Results showed that benzyl benzoate and its metabolites can be transported to the placenta and ultimately into the fetus. Mutagenicity studies of benzyl benzoate showed that it did not induce unplanned RNA synthesis in rat hepatocytes. This chemical did not cause hormonal damage or induce mutations in mammalian cells in vitro. Interactions During cyproterone acetate administration, the use of benzyl benzoate as an excipient resulted in detectable morphological changes at the ultrastructural level of the adrenal cortex. A 4:1 mixture of castor oil and benzyl benzoate induced intracellular and intercellular alterations. Changes were observed in the shape, size, and matrix of mitochondria in the zona fasciculata. Intercellular alterations affected the morphology of macrophages in the zona fasciculata and zona reticularis. Castor oil and benzyl benzoate carriers are believed to induce stress-induced changes. Non-human Toxicity Values Rats: Oral LD50: 1700 mg/kg Rats: Dermal LD50: 4 g/kg Mice: Oral LD50: 1400 mg/kg Cats: Oral LD50: 2240 mg/kg For more complete non-human toxicity data for benzyl benzoate (11 in total), please visit the HSDB record page.

Benzyl benzoate is a benzoic acid ester formed by the condensation of benzoic acid and benzyl alcohol. It has been isolated from plants of the genus Acer. Benzyl benzoate is used as an insecticide, acaricide, and plant metabolite for scabies. It is a benzyl ester and benzoic acid ester, functionally related to benzoic acid. Benzyl benzoate was one of the early drugs used to treat scabies. Scabies is a skin infection caused by the scabies mite (Sarcoptes scabiei). It is characterized by intense itching (especially at night), the appearance of red spots, and can lead to secondary infections. Benzyl benzoate is lethal to the scabies mite and is therefore used to treat scabies. It is also used to treat lice infestations on the head and body. Due to its irritant properties, benzyl benzoate is not a first-line drug for treating scabies. Benzyl benzoate has been reported to be found in the tea tree (Camellia sinensis), the Chinese mitten crab (Desmos chinensis), and other organisms with relevant data. Drug Indications Used to kill lice and mites that cause scabies. Mechanism of Action Benzyl benzoate is toxic to the nervous system of the parasites, leading to their death. It is also toxic to mite eggs, but the exact mechanism of action is unclear. In vitro studies have shown that benzyl benzoate kills scabies mites within 5 minutes. Therapeutic Uses Benzyl benzoate can be used as an alternative to topical treatment for scabies and has also been used to treat head lice (lice infestation). Benzyl benzoate emulsion, approximately 28% (w/w), for external use. This product is not for oral administration. Shake well before use. Scabies mite killer, lice killer. Veterinary use: Acaricide, lice killer. Contraindicated in cats.

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Drug Warnings
Animal studies have shown that oral administration of high doses of benzyl benzoate can lead to progressive motor incoordination, central nervous system excitation, seizures, and death.

Topical application of benzyl benzoate at appropriate doses has low toxicity. Mild local irritation (especially of the male genitals), itching, and allergic skin reactions may occur; avoid contact with the face, eyes, mucous membranes, and urethra. Repeated use of benzyl benzoate often causes contact dermatitis.

Contraindicated in patients with hypersensitivity to benzyl benzoate.

Benzyl benzoate should not be applied to acutely inflamed skin or broken, oozing skin. If primary irritation or allergic reaction occurs, discontinue treatment and wash thoroughly with soap and water.

Veterinarian: Cats are particularly sensitive to benzyl benzoate and therefore it is contraindicated in cats. The most prominent characteristic is nervous excitation. Clinical symptoms are similar to benzoic acid poisoning.

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Pharmacodynamics
Benzyl benzoate is one of the older formulations used to treat scabies.
Scabies is a skin infection caused by the scabies mite (Sarcoptes scabiei). It is characterized by intense itching (especially at night), the appearance of red spots, and can lead to secondary infections. Benzyl benzoate is lethal to the scabies mite and is therefore used to treat scabies. It can also be used to treat lice infestations on the head and body. However, because benzyl benzoate is irritating, it is not a first-line treatment for scabies.

C14H12O2

212.2439

212.083

120-51-4

Benzyl benzoate-d5;347840-01-1;Benzyl benzoate-d12;352431-26-6

2345

Leaflets or oily liquid
Water-white liquid
Colorless, oily liquid
Clear, colorless liquid

1.1±0.1 g/cm3

324.1±11.0 °C at 760 mmHg

18 °C

147.8±0.0 °C

0.0±0.7 mmHg at 25°C

1.579

3.97

0

2

4

16

213

0

O(C(C1C([H])=C([H])C([H])=C([H])C=1[H])=O)C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H]

SESFRYSPDFLNCH-UHFFFAOYSA-N

InChI=1S/C14H12O2/c15-14(13-9-5-2-6-10-13)16-11-12-7-3-1-4-8-12/h1-10H,11H2

benzyl benzoate

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 : ≥ 50 mg/mL (~235.58 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.78 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 (11.78 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 (11.78 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.)