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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 17 - 20, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study followed OECD protocol 404 and was conducted under various GLP assurances

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test substance consisted of white crystals and was stored at room temperature. Prior to use, the
test substance was ground with a mortar and pestle. In order to insure adequate skin contact with the
skin, the sample was applied as a dry paste (75% w/w minture in mineral oil). Purity was noted to be 99.6%.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Number of Animals: 3
Sex: 2 Males and I Female. The female assigned to test was nulliparous and nonpregnant.
Species/Strain: Rabbit/New Zealand albino.
Age: Young adult.
Source: Received from Robinson Services, Inc. Clemmons, NC on January 25, 2006.

Housing: The animals were singly housed in suspended stainless steel caging with mesh floors Litter paper was placed beneath the cage and was
changed at least three times per week.
Animal Room Temperature Range: 19-24°C
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 23 days
Food: Pelleted Purina Rabbit Chow #5326
Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: mineral oil
Controls:
no
Amount / concentration applied:
Prior to application, the test substance was ground to a powder with a mortar and pestle then moistened with mineral oil to achieve a dry paste by
preparing a 75% w/w mixture. Five-tenths of a milliliter of the test substance (0.67 g of the test mixture) was placed on a l-inch x l-inch, 4-ply gauze
pad and applied to one 6-cm2 intact dose site on each animal.
Duration of treatment / exposure:
4 hours
Observation period:
Individual dose sites were scored at approximately 30-60 minutes, 24, 48, and 72 hours after patch removal.
Number of animals:
3
Details on study design:
On the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to
application, the animals were examined for health and the skin checked for any abnormalities. Three healthy animals without pre-existing skin
irritation were selected for test.

Prior to application, the test substance was ground to a powder with a mortar and pestle then moistened with mineral oil to achieve a dry paste by
preparing a 75% w/w mixture. Five-tenths of a milliliter of the test substance (0.67 g of the test mixture) was placed on a l-inch x l-inch, 4-ply gauze
pad and applied to one 6-cm2 intact dose site on each animal. The pad and entire trunk of each animal were then wrapped with semi-occlusive
3-inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated
cages. After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites
were gently cleansed of any residual test substance.

The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and
behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Individual dose sites were scored according to the Draize scoring system at approximately 30-60 minutes, 24, 48, and 72 hours after patch removal. The classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minute, 24, 48, and 72-hour scoring
intervals and dividing by the number of evaluation intervals.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hrs
Score:
1.6
Max. score:
3
Reversibility:
fully reversible within: 72 hrs
Other effects:
All animals appeared active and healthy during the study. Apart from the dermal irritation noted, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior.

Any other information on results incl. tables

 

 

Incidence of Irritation

Time After Patch Removal

 

Erythema

 

Edema

30-60 minutes

3/3

3/3

24 hours

3/3

3/3

48 hours

2/3

0/3

72 hours

0/3

0/3

 

 

TimeAfterPatch Removal

Severity of Irritation-Mean Score

30-60 minutes

3.0

24 hours

2.7

48 hours

0.7

72 hours

0

 

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, 2,2,4,4-Tetramethyl-1,3-cyclobutanediol is classified as slightly irritating to the skin.
Executive summary:

All three animals appeared active and healthy during the study. Apart from the dermal irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. Within one hour of patch removal, all three treated sites exhibited well-defined erythema and very slight edema. The overall incidence and severity of irritation decreased with time. All animals were free of dermal irritation by 72 hours. The Primary Dermal Irritation Index was 1.6 which correlates to a classification of slightly irritating.