Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 30 2001 - July 23 2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Guidance on Safety Assessment of New Cosmetics (Japan Cosmetic Industry Association, technical materials No.92, 1991
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
other: Crj:CD(SD)IGS
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Atsugi Breeding Center, Charles River Japan Inc.
- Age at study initiation:6 weeks
- Weight at study initiation: male 193-212 g, female 131-151 g
- Fasting period before study: ca. 18 hours
- Housing: Individually housed, in stainless steel bracket cages for rats
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 or 200 mg/mL


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: According to the Guidance on Safety Assessment of New Cosmetics, 2000 mg/kg was set for the high dose group, 1000 mg/kg for the low dose group, and olive oil for the control group.
Doses:
vehicle at 0 mg/kg, 1000 and 2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs and mortality at 15, 30 minutes, 1, 3 and 6 hours after treatment on the day of treatment and thereafter once daily. Animals were weighed on the day of treatment and on days 2, 3, 4, 8, 11 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The body surface and the intracranial, intrathoracic and intra-abdominal organs were macroscopically examined. Histopathological examination was not performed because necropsy did not reveal any abnormal changes.
Statistics:
The body weight measurements obtained in the study were averaged and standard deviation was calculated for each group, which were analysed for homogeneity of variance by F-test. Since the results showed homogenous variance, Student t-test was performed. There was no statistical significance noted.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred through the observation period in either males or females in all the groups including the control group in response to test article administration.
Clinical signs:
No clinical signs caused by the test substance were observed. Watery diarrhoea was observed in males and females in all groups, which ceased by day 2 of treatment, after which no special changes were observed.
Body weight:
During the observation period, there was no statistical difference in body weight measurements between the groups. The body weight of each group increased favourably.
Gross pathology:
There were no remarkable findings at necropsy in any group of animals.
Other findings:
None reported.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Not classified according to Regulation (EC) No 1272/2008
Conclusions:
An LD50 value of >2000 mg/kg bw in rats of both sexes is reported in a study equivalent to current OECD guideline, which was not GLP compliant.