Acetophenone

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study meets generally accepted principles as a study investigating specific pathways of metabolism by excretion of a single metabolite in urine and exhalation of CO2; minor restrictions: qualitative identification of mandelic acid by TLC, less detailed documentation of test methods and test results; study acceptable as weight of evidence study

Data source

Reference

Reference Type:

publication

Title:

Reaction pathways of in vivo stereoselective conversion of ethylbenzene to mandelic acid

Author:

Sullivan HR, Miller WM, McMahon RE

Year:

1976

Bibliographic source:

Xenobiotica 6: 49-54

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

Excretion of mandelic acid analyzed in urine by preparative TLC after cleavage of conjugates; after dosing with 14C-acetophenone (label at methyl carbon) exhalation of 14CO2 was followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Acetophenone

EC Number:

202-708-7

EC Name:

Acetophenone

Cas Number:

98-86-2

Molecular formula:

C8H8O

IUPAC Name:

1-phenylethanone

Details on test material:

boiling point: 200-202 degrees C

Radiolabelling:

yes

Remarks:

14C at the methyl group

Test animals

Species:

rat

Strain:

other: Albino

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Duration and frequency of treatment / exposure:

single

Doses / concentrations

Remarks:

Doses / Concentrations:
100 mg/kg

No. of animals per sex per dose / concentration:

8

Details on dosing and sampling:

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: for 24 hrs
- From how many animals: (samples pooled or not) 8
- Method type(s) for identification: isolation of mandelic acid by preparative thin layer chromatography
- Limits of detection and quantification: not specified

TREATMENT FOR CLEAVAGE OF CONJUGATES
Hydrolysis of conjugates by incubation with aryl sulfatase and ß-glucuronidase

OTHER INVESTIGATIONS
Exhalation of 14CO2 was followed for up to 13 hrs.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

in urine: mandelic acid;
exhalation of 14CO2 accounted to 10 % during first 4 hrs and to 30 % during 13 hrs post application indicating formation of benzoic acid as further metabolite

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Acetophenone is metabolized to mandelic acid and the formation of benzoic acid is indicated by exhalation of CO2.

Executive summary:

In rats, acetophenone is metabolized to mandelic acid after intraperitoneal injection of ¹⁴C-methyl labeled acetophenone (100 mg/kg). The formation of benzoic acid is indicated by exhalation of CO₂ (10% during the first 4 hrs and 30% during 13 hrs post application).