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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 - 19 Nov 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
missing information about environmental conditions and acclimatisation period; occlusive instead of semi-occlusive dressing

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted February 24, 1987
Deviations:
yes
Remarks:
missing information about environmental conditions and acclimatisation period; occlusive instead of semi-occlusive dressing
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 1-[(1R*,6S*)-2,2,6-trimethylcyclohexyl]hexan-3-ol and 1-[(1S*,6S*)-2,2,6-trimethylcyclohexyl]hexan-3-ol
EC Number:
947-716-8
Molecular formula:
C15H30O
IUPAC Name:
Reaction mass of 1-[(1R*,6S*)-2,2,6-trimethylcyclohexyl]hexan-3-ol and 1-[(1S*,6S*)-2,2,6-trimethylcyclohexyl]hexan-3-ol

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Weight at study initiation: 2.0 - 2.6 kg (males) and 2.1 - 2.4 kg (females)
- Housing: individually in suspended wire mesh cages
- Diet: Purina Rabbit Chow (Diet #5321), provided daily
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the dorsal area of the trunk
- % coverage: 10%
- Type of wrap if used: plastic wrap secured with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: The residual test article was gently washed off with distilled water prior to dermal observations.
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The test sides were scored for dermal irritation at 24 hours post dose and on days 7 and 14 using the numerical Draize scale. The animals were observed 1, 2 and 4 hours post dose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality. Body weights were recorded pretest, weekly and at death or termination.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology with preservation of abnormal tissues in 10% buffered formalin
Statistics:
LD50, 95% Confidence Limits, dose response curve and slope were calculated by method of Litchfield and Wilcoxon.

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:
One male animal died at day 11 post-dose.
Clinical signs:
Diarrhea occured in 2/5 males and 1/5 females within day 8 -14 post-dose. Male animal which died on day 12 post-dose showed predeath physical signs of diarrhea and lethargy, which is attributed to stress-induced gastrointestinal abnomalities common in New Zeeland White rabbits.
Body weight:
Body weight gains were within the normal ranges during the whole study period.
Gross pathology:
Necropsy of the dead animal revealed abnomalities in the intestines (filled with fluid) and treated skin, as well as soiling of the anogenital area. Necropsy results of survivors revealed treated skin abnormaties in 8/9 animals, two of which also exhibited liver abnormalities (nodules on liver). One animal appeared normal at necropsy.
Other findings:
Dermal reactions, well defined to moderate on day 1, were absent to severe on day 7 and absent on day 14.

Any other information on results incl. tables

Table 1. Results of acute dermal toxicity

Dose

[mg/kg bw]

Mortality

Clinical signs

 

n = 5

n = 5

Males

2000

1/5

2/5

Females

2000

0/5

1/5

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity study thre LD50 value was > 2000 mg/kg bw in male and female rabbits.
Executive summary:
The acute dermal toxicity of the test substance was assessed in a limit test performed in 5 male and 5 female new Zealand White rabbits according to OECD Guideline 402 and in compliance with GLP (1993). The test substance was applied at a single dose of 2000 mg/kg bw to the clipped dorsal area of the trunk of the animals and held in contact to the skin with a gauze patch and a plastic wrap around the torso for 24 hours. Animals were observed for mortality, general clinical condition and alterations of the administration area (erythema and/or edema) for a 14-day period. Body weights were recorded on the day of administration and on days 7 and 14 thereafter. Macroscopic examination was performed at the end of the observation period at terminal sacrifice. Nine of ten animals survived the 2000 mg/kg bw dermal application. One male died on day 11 after physical signs of diarrhea and lethargy which were attributed to stress-induced gastrointestinal tract abnormalities common in New Zealand White rabbits. Necropsy of the dead animal revealed abnormalities of intestine and treated skin, as well as soiling of the anogenital area. Diarrhea was the only abnormal physical sign noted in the survivors. Body weight gain was not affected by test substance administration. Erythema (grade 2-3) and edema (grade 2-3) of treated skin areas were observed on day 1 and was absent for on day 7. Erythema was fully regressed on day 14. Necropsy of survivors revealed treated skin abnormalities in 8/9 animals, two of which also exhibited liver abnormalities. Based on the results of this study, the dermal LD50 value for acute toxicity was determined to be > 2000 mg/kg bw in rabbits.

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