Registration Dossier

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: Acceptable well-documented publication

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Food Flavourings 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 AA, Brouwer JB
Year:
1967
Bibliographic source:
Fd. Cosmet. Toxicol. 5: 141
Reference Type:
secondary source
Title:
Die Situation in der gesundheitlichen Beurteilung der Aromatisierungsmittel für Lebensmittel
Author:
Bär F and Griepentrog F
Year:
1967
Bibliographic source:
Med. Ernaer., Vol. 8, pp244-251
Reference Type:
secondary source
Title:
Fragrance Raw Materials Monographs
Author:
Opdyke DLJ
Year:
1974
Bibliographic source:
Food and Cosmetics Toxicology, Vol. 12: 881-882
Reference Type:
secondary source
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
subchronic to chronic feeding study
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Geraniol Extra
- Isomers composition:
3,7-Dimethyl-2,6-octadienol
and 3,7-Dimethyl-1,6-octadienol

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: individually

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
112 days at 10000 ppm; 189-196 days at 1000 ppm
Frequency of treatment:
continuously in diet
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 or 10000 ppm (ca. 55 or 550 mg/kg/day)
Basis:
nominal in diet
No. of animals per sex per dose:
5 male and 5 female
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Time schedule for examinations: weekly


HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination of study
- Parameters checked: white cell counts, red cell counts, hemoglobin and hematocrits
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes; liver, kidneys, spleen, heart, testes, abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle

- Organ weights of liver, kidneys, spleen, heart and testes were recorded
- Detailed microscopic examinations in the subacute study were done on 6 or 8 animals evenly divided by sex, in the high dose group and control group, if multiple doses were tested.
- If changes attributable to the test compound were found in the high dose group, additional animals on lower dosage levels were examined.
- For animals from the long-term study more extensive histopathological study was done.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Haematological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
> 10 000 ppm
Sex:
male/female
Basis for effect level:
other: No effects observed at highest tested dose level
Dose descriptor:
NOEL
Effect level:
> 550 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: No effects observed at highest tested dose level

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion