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Toxicological information

Repeated dose toxicity: oral

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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

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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 1000, 2500 and 10000 ppm
Basis:
nominal in diet
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

open allclose all
Dose descriptor:
NOEL
Effect level:
100 000 ppm
Based on:
test mat.
Remarks:
acetophenone
Sex:
male/female
Basis for effect level:
other: No effect
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
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.