Benzyl propionate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

BENZYL ACETATE CARCINOGENICITY, METABOLISM, AND DISPOSITION IN FISCHER 344 RATS AND B6C3F1 MICE

Author:

K.M. ABDO et al.

Year:

1985

Bibliographic source:

Toxicology, 37 (1985) 159--170

Materials and methods

Principles of method if other than guideline:

Metabolism and disposition studies

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl acetate

EC Number:

205-399-7

EC Name:

Benzyl acetate

Cas Number:

140-11-4

Molecular formula:

C9H10O2

IUPAC Name:

benzyl acetate

Details on test material:

- Name of test material (as cited in study report): Radioactive benzyl acetate (ring labeled-14C
- Molecular formula (if other than submission substance): C9H10O2
- Molecular weight (if other than submission substance): 150.1745
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): NA

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

For the single dose studies, groups of 3 rats were given a single oral dose of 5, 50, or 500 mg/kg in 5 ml corn oil/kg body weight; radioactivity given was 1 µCi/100 g body weight. For the repeated dose studies, 3 rats were given unlabeled benzyl acetate in corn oil by garage at 500 or 1000 mg/kg once a day, 5 days/week for 2 weeks.
Twenty-four hours prior to sacrifice, each animal received the prescribed dose containing radiolabeled benzyl acetate.

Duration and frequency of treatment / exposure:

For the repeated exposure: once a day, 5 days/week for 2 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
For single oral dose: 5, 50, or 500 mg/kg in 5 ml corn oil/kg body weight
For repeated dose: 500 or 1000 mg/kg

No. of animals per sex per dose / concentration:

3 male Rats

Control animals:

not specified

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Benzyl acetate was absorbed from the gastrointestinal tract of rats. This capacity for absorption was unaffected by the amount or number of doses administered.

Main ADME results 2

Type:

metabolism

Results:

The major metabolite was hippuric acid accounting for >90% of the total excreted in the urine of all dose groups. A minor metabolite, benzyl mercapturic acid, was also identified in the urine of rats.

Main ADME results 3

Type:

excretion

Results:

Benzyl acetate was excreted primarily in urine; nearly 90% of the administered dose was recovered in 24 h. Little radioactivity (0.3--1.3% of dose} was recovered in the feces.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Major metabolite: hippuric acid
Minor metabolite: benzyl mercapturic acid


No benzyl acetate-derived radioactivity was found in any of the tissues analyzed 24 h post-exposure. Additionally no benzyl acetate was detected in the urine of any animal given this compound.

Any other information on results incl. tables

Absorption:Benzyl acetate was absorbed from the gastrointestinal tract of rats. This capacity for absorption was unaffected by the amount or number of doses administered.

Distribution:No details available.

Metabolism:The major metabolite was hippuric acid accounting for >90% of the total excreted in the urine of all dose groups. A minor metabolite, benzyl mercapturic acid, was also identified in the urine of rats. All these metabolites were identified by cochromatography with synthetic standards.

Excretion:Benzyl acetate was excreted primarily in urine; nearly 90% of the administered dose was recovered in 24 h. Little radioactivity (0.3--1.3% of dose} was recovered in the feces. This clearance pattern was not affected by repeated dosing 5 days/week for 2 weeks at 500 mg/kg in rats. Elimination of this compound as COs or volatiles was not determined following oral dosing. Less than complete recovery of radioactivity is attributed to losses during administration or incomplete recovery of urine or tissues.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on results complete clearance indicates that benzyl acetate is readily absorbed and excreted and shall have Low bio-accumulation potential based on the study results.

Executive summary:

The metabolism and disposition studies in rats and mice indicated that benzyl acetate was readily absorbed from the gastrointestinal tract; metabolized to hippuric acid, mercapturic acid, and traces of unidentified metabolites and excreted in urine. The relative amounts of the dose absorbed. metabolized, and excreted were apparently unaffected by the size or the number of doses administered. There was no evidence to indicate any reduction or saturation of the metabolic capacity of F344 rats for the complete and rapid metabolism and clearance of this compound over the dose range tested (5--500 mg/kg for rats). No benzyl acetate-derived radioactivity was found in any of the tissues analyzed 24 h post-exposure.Thus,such complete clearance indicates that benzyl acetate is readily absorbed and excretedand shall haveLow bio-accumulation potential based on the study results.