4'-methylacetophenone

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-GLP, pre-OECD TG study with sufficient detail in documentation

Data source

Reference

Reference Type:

publication

Title:

Food flavorings and compounds of related structure. II. Subacute and chronic toxicity

Author:

Hagan EC, Hansen WH, Fitzhugh OG, Jenner PM, Jones WI, Taylor JM, Long EL, Nelson AM and Brouwer JB

Year:

1967

Bibliographic source:

Food and Cosmetics Toxicology, 5(2), 141-157

Materials and methods

Principles of method if other than guideline:

The study was conducted prior to the publication of OECD TGs. Rats received daily oral doses of the test substance dissolved in corn oil for a period of 17 weeks.

GLP compliance:

no

Limit test:

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

IUPAC Name:

1-phenylethanone

Details on test material:

Name: Acetophenone (methyl 1-phenyl ketone)
Purity: commercial product
No further details provided

Test animals

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not reported
- Age at study initiation: weanling
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: individually in wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- not reported

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
appropriate amounts of test substance were weighed and mixed in the diet

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Loss of acetophenone from laboratory animal diet during a 7-day period: 31 %
Percentage loss = 100-(100xday 7 recovery/day 0 recovery)

Duration of treatment / exposure:

17 weeks

Frequency of treatment:

Continuously

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 1000, 2500 and 10000 ppm
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 75, 118, 750 mg/kg bw/day
Basis:
other: calculated from assumed body weight (400 g) and food consumption (30 mg/day/rat)

No. of animals per sex per dose:

10 males and 10 females

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: not reported

Positive control:

No

Examinations

Observations and examinations performed and frequency:

Body weight, food intake and general conditions: every week
Haematology (white cell count, red cell count, haemoglobins, haematocrits): after three months
Gross pathology: at termination of study
Histopathology: at termination of study

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

Not reported

Statistics:

Not reported

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

There was no effect on growth or haematology, and no macroscopic or microscopic change in the tissues.

Effect levels

1

Dose descriptor:

NOEL

Effect level:

100 000 ppm

Based on:

test mat.

Remarks:

acetophenone

Sex:

male/female

Basis for effect level:

other: No effect

2

Dose descriptor:

NOEL

Effect level:

518 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

acetophenone

Sex:

male/female

Basis for effect level:

other: No effect observed at the highest received dose = 750 mg/kg bw/day, but assuming 31 % loss of acetophenone from laboratory animal diet during a 7-day period

3

Dose descriptor:

NOEL

Effect level:

578 mg/kg bw/day (nominal)

Based on:

other: 4'-methylacetophenone

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Oral repeated exposure of rats to acetophenone by feeding over a period of 17 weeks resulted no adverse effects up to 100000 ppm in the diet. Considering 31 % of acetophenone loss from laboratory animal diet during a 7-day period, the corrected NOEL is 518 mg/kg bw/day.

Executive summary:

The oral repeated dose toxicity of acetophenone to male and female Osborne-Mendel rats was studied over a period of 17 weeks. The test substance was added in the food at doses of 1000, 2500 and 100000 ppm to ten males and ten females in each dose group. A untreated control group was investigated in parallel. All animals were weanling at the beginning of the study. The body weight, food consumption and general condition of animals were recorded regularly. Haematological investigations were performed after 3 months. At the end of the study all animals were sacrificed. Gross pathology was performed on every rat and organs were weighed. Sections were prepared from relevant organs for histopathological studies, which were performed for a representative fraction of animals (6 or 8) in high dose and control groups evenly divided by sex. No effects on growth or haematology, and no macroscopic or microscopic change in the tissues were found at the end of the study up to 100000 ppm dose level. It was concluded that the no-effect level (NOEL) was at 100000 ppm or 750 mg/kg bw/day in male and female Osborne-Mendel rats. Considering 31 % of acetophenone loss from laboratory animal diet during a 7-day period, the corrected NOEL is 518 mg/kg bw/day.