Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-09-8 to 1992-09-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1981-05-12
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1984
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1992-06-11
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol
EC Number:
701-039-2
Cas Number:
156324-78-6
Molecular formula:
C13H24O4
IUPAC Name:
2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. ten to fourteen weeks old
- Weight at study initiation: males: 209 - 225 g; females: 215 - 223 g
- Housing: individually in suspended polypropylene cages furnished with softwood sawdust, during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (ad libitum): Rat and Mouse Expanded Diet No. 1
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 22 °C
- Relative humidity: 50 - 75%
- Air changes: approx. 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Remarks:
B.P.
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks were clipped free of hair (approx. 5 cm x 4 cm)
- % coverage: approx. 10 % of the total body surface area was treated with the test substance, which has previously been moistened with the vehicle
- Type of wrap: piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of BLENDERM wrapped around each end.

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin and surrounding hair wiped with cotton wool moistened with arachis oil to remove any residual test material
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
death and overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days (adverse dermal reactions were also noted)
individual body weights: prior to application on Day 0 and on Days 7 and 14

- Necropsy of survivors performed: yes, at the end of the study the animals were sacrificed and subjected to gross pathological examination.
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:
not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Moderate erythema was noted at the treatment sites of all females two and three days after dosing. Desquamation was also noted at the treatment site of one female three to five days after dosing.
No signs of skin irritation were noted in males during the study.
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (male and female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the dermal route.
Executive summary:

The acute dermal toxicity of the substance was investigated according to the OECD guideline 402 (1981). The substance was applied to clipped skin of five male and five female Sprague-Dawley rats at a dose level of 2000 mg/kg bw and covered with a semi-occlusive dressing. The application site had been moistened with arachis oil B.P. before application.The application site was exposed for 24 hours and the test sites were cleaned using a cotton wool moistened with arachis oil to remove any residual test substance. Clinical signs, mortality, adverse dermal reactions and body weight were recorded during the 14 day observation period. All animals were subjected to necropsy at the end of the study.

No mortality occurred and no signs of systemic toxicity were noted during the study. Moderate erythema was noted at the treatment sites of all females two and three days after dosing. Desquamation was also noted at the treatment site of one female three to five days after dosing. No signs of skin irritation were noted in males during the study. Furthermore, all animals showed expected gain in bodyweight during the study and no abnormalities were noted at necropsy.

Thus, the LD50 was considered to be greater than 2000 mg/kg bw for male and female rats. According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not acutely toxic via the dermal route.