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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication/ study report which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Carciogenesis Studies of Food Grade Geranyl Acetate (71% Geranyl Acetate, 29% Citronellyl Acetate) (CAS No. 105-87-3) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
Author:
US National Institutes of Health
Year:
1987
Bibliographic source:
National Toxicology Program - Technical Report Series No. 252

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: Specifications for the Conduct of Studies to Evaluate the Toxic and Carcinogenic Potential of Chemical, Biological, and Physical Agents in Laboratory Animals for the National Toxicology Program (NTP)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): food-grade geranyl acetate
- Composition of test material: 71% geranyl acetate (CAS 105-87-3) and 29% citronellyl acetate (CAS 150-84-5) was reported for the lot used for chronic studies. No accurate determination of the content of these two components was made for the lot used in the subacute and subchronic studies.
- Lot No.: 70201 (Elan Chemical Co, Newark, NJ)
- Impurities: approx. 1%
- Storage condition of test material: in the dark at 5°C

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries, Indianapolis, IN, USA
- Age at study initiation: 5 weeks
- Housing: 5 animals/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 40-60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
once daily, 5 times/week
Doses / concentrations
Remarks:
Doses / Concentrations:
250, 500, 1000, 2000, 4000 mg/kg bw
Basis:

No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
- morbidity and mortality: time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

Sacrifice and pathology:
NECROSCOPY: Yes, animals survived to the end of study and dead animals
HISTOPATHOLOGY: Yes, animals of control and top dose group
gross lesions, tissue masses, abnormal lymph nodes, skin, mandibular lymph nodes, mammary gland, salivary gland, thigh muscle, sciatic nerve, bone marrow, thymus, larynx, trachea, lungs and bronchi, heart, thyroid, parathyroid, esophagus, stomach, duodenum, jejunum, ileum, colon, mesenteric lymph nodes, liver, gallbladder, pancreas, spleen, kidneys, adrenals, urinary bladder, seminal vesicles/ prostate/ testes or ovaries/ uterus, brain, pituitary, and spinal cord.
Tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin.

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
- 500 mg/kg bw: 1/10 male died, due to error of gavage
- 4000 mg/kg bw: 1/10 female and 2/10 male died
- No signs of toxicity were reported

BODY WEIGHT AND WEIGHT GAIN
The mean body weight of the rats of the 4000 mg/kg bw group was decreased compared to control (19 % for the males, 8 % for the females).

NECROPSY:
- 4000 mg/kg bw: 3 males showed reddened mucosa of the stomach

HISTOPATHOLOGY:
No test substance related effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: = 1420 mg/kg bw/day (nominal) Geranyl acetate

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion