Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According to OECD guideline. No data on GLP.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1971
Report Date:
1970

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity >97 %

Test animals

Species:
rat
Strain:
other: CFE
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bush Boake Allen Ltd., London
- Weight at study initiation: 100-120 g (male) and 90-105 g (female)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 1ºC
- Humidity (%): 50-60%

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 5 ml total dose/kg/day
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
13 weeks ( 0, 15, 90 or 270 mg/kg bw/day)
2 to 6 weeks (0, 90 or 270 mg/kg bw/day)v
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 15, 90 or 270 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
15 male and 15 female: 0, 15, 90 or 270 mg/kg bw/day
5 male and 5 female: 0, 90 or 270 mg/kg bw/day
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes
- Time schedule for examinations: weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after sacrifice

URINALYSIS: Yes
- Time schedule for collection of urine: collected during the final week and week 6
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
(No deaths and no abnormalities in behaviour or appearance occurred during the study)
Mortality:
no mortality observed
Description (incidence):
(No deaths and no abnormalities in behaviour or appearance occurred during the study)
Body weight and weight changes:
no effects observed
Description (incidence and severity):
(no significant differences between test and control animals)
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
(no significant differences between test and control animals)
Food efficiency:
effects observed, treatment-related
Description (incidence and severity):
(no significant differences between test and control animals)
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
(Only in males treated with the highers dose increase of mean water consumption was observed)
Haematological findings:
no effects observed
Description (incidence and severity):
(no differences between the test and control groups )
Urinalysis findings:
no effects observed
Description (incidence and severity):
(The females treated with IBA gave results similar to those of female controls throughout. In males there were no differences between control and IBA-treated rats at week 2 but at week 6 cell excretion was increased in rats receiving 270 mg/kg bw/day )
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
(there was increase of weight of some organs.)
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
(Histological changes associated with IBA treatment were confined to treatment at the 270 mg/kg bw/day level.)

Effect levels

Dose descriptor:
NOEL
Effect level:
15 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOEL for Iosbornyl acetate (13 weeks ) was 15 mg/kg bw/day.
Executive summary:

Repeated dose toxicitystudy (oral route) of Isobornyl acetate was performed according to OECD guideline 408. The substance was dissolved in corn oil and administered daily to rats by stomach tube in doses: 0 (control), 15, 90 or 270 mg/kg body weight/day during 13 weeks. There were no differences between treated and control animals in the rate of body-weight gain, the food intake or the results of haematological investigations. In male rats given 270 mg/kg bw/day there was a decrease in renal concentrating ability, an increase in water intake, exfoliation of renal tubular cells, increased kidney weight and vacuolation of the renal tubular cells. Signs of nephrotoxicity were also seen with daily doses of 90 mg/kg bw/day.

Vacuolation of the epithelium of the intrahepatic bile-duct and increase in liver weights were found at 270 mg/kg bw/day. The caecum were also enlarged at this dosage level.

The no-effect level found was at 15 mg/kg bw/day.