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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability 2 is assigned because study predates current guidelines and GLP but is otherwise adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Food Flavourings and Compounds of Related Structure. II. Subacute and Chronic Toxicity
Author:
Hagan EC. et al
Year:
1967
Bibliographic source:
Fd Cosmet. Toxicol. Vol 5, pp. 141-157. Pergamon Press 1967.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
p-menth-1-en-8-yl acetate
EC Number:
201-265-7
EC Name:
p-menth-1-en-8-yl acetate
Cas Number:
80-26-2
Molecular formula:
C12H20O2
IUPAC Name:
1-methyl-1-(4-methylcyclohex-3-en-1-yl)ethyl acetate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Terpinyl acetate

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: Individually in wire cages
- Diet: Ad libitum
- Water: Ad libitum

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
7% loss of food flavouring during a 7-day period
Duration of treatment / exposure:
20 weeks
Frequency of treatment:
Fresh diets were made and distributed weekly
Doses / concentrations
Remarks:
Doses / Concentrations:
1000, 2500, 10000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
The rat's weight, food intake and general condition were recorded every week. Haematological examinations were made at termination
Sacrifice and pathology:
At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 % buffered formalin-saline solution for histopathological
examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. Detailed microscopic examinations in the subacute studies were generally done on 6 or 8 rats, evenly divided by sex, from the high dose group and the control group. If changes attributable to the test compound were found in the high dose group, additional animals on lower dosage levels were examined as indicated.

Results and discussion

Results of examinations

Details on results:
No effect on growth or haematology, and no macroscopic or microscopic change in the tissues in the 10000 ppm exposure group.
No effect on growth or haematology, and no macroscopic change in the tissues in the 2500 and 1000 ppm exposure groups. No microscopic examination performed.

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 400 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: The 400 mg/kg is the derived value based on the 10000 ppm dietary dose)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No effects were observed in a 20-weeks repeated dose toxicity study in rats at the tested concentrations (up to 10000 ppm).
Executive summary:

In a 20 -weeks oral exposure study Osborne-Mendel rats (10/dose/sex) were administered alpha-Terpinyl Acetate via diet intake at concentrations of 0 (control), 10000, 2500 and 1000 ppm. Animals were then observed for mortality, weight, food intake and general condition. Haematological examinations were made at termination. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. Detailed microscopic examinations was done on the animals from the high dose group and the control group. No effect on growth or haematology, and no macroscopic or microscopic change in the tissues in the 10000 ppm exposure group were observed. No effect on growth or haematology, and no macroscopic change in the tissues in the 2500 and 1000 ppm exposure groups. No microscopic examination was performed on rats exposed to 2500 and 1000 ppm. According to the Guidance on information and chemical safety assessment R8 table R 8 -17, rats eat 40 to 50 mg/kg bw/day. 10000 ppm is equivalent to 1% in the diet. Consequently, rats exposed to 10000 ppm in the diet consumed between 400 and 500 mg Terpinyl-Acetate-Alpha per kg bodyweight per day. Therefore, the NOAEL was calculated to be 400 mg/kg bw.