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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:
supporting study
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:
study report
Title:
Unnamed
Year:
1987

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:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries, Indianapolis, IN
- Age at study initiation: 6 weeks
- Housing: 5/cage
- Diet and 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 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
125, 250, 500, 1000, 2000 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly (including palpation for tissue masses or swelling)

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

OBSERVATION OF MORTALITY AND MORBIDITY: YES
- Time schedule: twice daily
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (all animals, unless precluded in whole or in part by autolysis or cannibalization)

HISTOPATHOLOGY: Yes (control and high-dose group animals)
- 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, duode- num, 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
- 2000 mg/kg bw/d: 7/10 males and 9/10 females died
- 0, 250, 500 mg/kg bw/d: 1 female per given dose group died due to error of gavage
- No other signs of toxicity were reported

BODY WEIGHT AND WEIGHT GAIN
- 2000 mg/kg bw: gain of weight of males slightly delayed

HISTOPATHOLOGY: NON-NEOPLASTIC
2000 mg/kg bw:
- liver, kidney and myocardium showed cytoplasmic vacuolization with lipid inclusions.
Liver: 7/10 m; 8/9 f
Kidney: 2/10 m; 4/9 f
Myocardium: 2/10m; 1/9f

- Stomach leasions including inflammation and edema
Stomach: 2/10m; 6/10f

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: = 290 mg/kg bw/day (nominal) citronellyl acetate

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion