Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 days
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliable without restriction; study was conducted according to Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (skin irritation), and GLPs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
-Test material (as cited in report): Nesterol
-Chemical name (as cited in report):2,2,4-Trimethyl-1 ,3-pentanediol-isobutyrate
-Purity: 99.5%
-Physical description: Clear colorless liquid
-Storage: Room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Test animals:
-Source: Froxfield (UK) Ltd., Petersfield, Hampshire, England
-Sex: 1 female and 2 males
-Age at receipt: approximately 12-17 weeks
-Weight at study initiation: 2.9-4.1kg
-Housing: Individually housed in metal cages with perforated floors
-Diet: SDS Stanrab (P) Rabbit Diet, ad libitum
-Water: local municipality, ad libitum
-Method of animal identification: individual numbered aluminium tag placed through the edge of one ear

Environmental Conditions:
-Temperature: approximately 19°C
-Humidity: 30-70%
-Photoperiod: 12 hour light/dark cycle
-Air exchanges: approximately 19 air exchanges per hour

In-Life Study Dates:
-Study Initiation Date: March 8, 1995
-Experimental Start Date: April 4, 1995
-Experimental Completion Date: April 17, 1995

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5ml of the neat test substance was applied under a 25 mm x 25 mm gauze pad
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3 animals; 1 female and 2 males
Details on study design:
Approximately 24 hours prior to test substance application, the hair was removed with electric clippers from the dorso-lumbar region exposing an area of skin approximately 100 mm X 100 mm of each rabbit. A 0.5 ml amount of the neat test substance was applied under a 25 mm X 25 mm gauze pad and the treatment site was covered with an Eslastoplast elastic adhesive for 4 hours. The animals were not restrained and were returned to their carge after treatment. At the end of the exposure period, the dressing and gauze pad were removed, the treatment site was washed with warm water (30° to 40°C) to remove any residual test substance and blotted dry with absorbent paper.

Clinical observations:
All animals were observed daily for signs of toxicity.

Dermal observations:
The skin of each rabbit was observed 1 hour, 24, 48, and 72 hours after test substance exposure. Observations for dermal reactions were observed daily for a total of 14 days.

Dermal observations were assessed using the following numerical system:
Erythema and eschar formation:
0-No erythema
1-Very slight erythema (barely perceptible)
2-Well-defined erythema
3-Moderate to severe erythema
4-Severe erythema (beet redness) to slight eschar formation (injuries in depth) preventing erythema reading

Edema formation:
0-No edema
1-Very slight edema (barely perceptible)
2-Slight edema (edges of area well-defined by definite raising)
3-Moderate edema (raised approximately 1 millimeter)
4-Severe edema (raised more than 1 millimeter and extending beyond the area of exposure)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 8 Days
Remarks on result:
not determinable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
not determinable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 14 Days
Remarks on result:
not determinable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 3 Days
Remarks on result:
not determinable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: Entire observation period (14 days)
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 14 Days
Remarks on result:
not determinable
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
male
Time point:
other: Entire observation period (14 days)
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
other: No edema was noted in animal #3.
Other effects:
Clinical signs: There was no toxicity noted in any animal during the study.

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Semiocclusive administration of Nesterol (0.5ml neat) to the backs of 3 (2 males and 1 female) New Zealand White Rabbits resulted in a mean erythema score of 1.66 in 2 of the 3 animals. The third animal had an average score of 1 during the same time period.

Nesterol is classified for Skin Irritation/Corrosion according to GHS as a mild irritant (category 3).
Executive summary:

In a dermal irritation study, three New Zealand White rabbits were each administered 0.5 mL of undiluted Nesterol to the clipped skin of the back for four hours under semiocclusion. The animals were then observed for a total of 14 days for signs of primary irritation (erythema and edema). During the observation period, the test substance caused very slight to well-defined erythema in three animals accompanied by very slight edema in one animal. Dryness and sloughing of the skin was noted in two animals starting on day 6 or 7 to day 13 when the skin of all animals was perceived as normal. Under the study conditions, Nesterol is classified as a mild irritant in New Zealand White Rabbits.