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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:
The study was performed between 27 April 1995 and 4 May 1995.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 17 July 1992
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
2,6-di-tert-butyl-4-nonylphenol
EC Number:
224-320-7
EC Name:
2,6-di-tert-butyl-4-nonylphenol
Cas Number:
4306-88-1
Molecular formula:
C23H40O
IUPAC Name:
2,6-di-tert-butyl-4-nonylphenol
Test material form:
liquid
Details on test material:
Clear colourless liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 99/26.12.94

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature under nitrogen

FORM AS APPLIED IN THE TEST (if different from that of starting material): clear colourless liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.30 to 2.88 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): Free access to food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd., Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: minimum acclimatisation period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 20 °C
- Humidity (%): 49 to 66%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
on the day before the test
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 hours
Observation period:
Up to 72 hours after exposure. An additional observation was made on day 7 to assess the reversibility of skin reactions.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal flank area
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: A quantity of 0.5 mL of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later. An additional observation was made on day 7 to assess the reversibility of skin reactions.

SCORING SYSTEM:
- Method of calculation: according to the following scale from Draize J.H., (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington D.C. p.31.

-Erythea and Eschar Formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to eschar formation (injuries in depth): 4
-Oedema Formation:
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema ( edges of area well defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe erythema (raised more than 1 mm and extending beyond exposure area): 4
Any other skin reactions, if present, were also recorded.
An additional observation was made on day 7 to assess the reversibility of skin reactions.


Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Remarks:
total mean (12 values) divided by 6
Basis:
mean
Time point:
other: 24 and 72-hour readings
Score:
3.5
Max. score:
8
Reversibility:
other: Desquamation was noted at two treated skin sites and crust formation, considered to be reversible, at one treated skin site at the 7-day observation.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Well-defined erythema was noted at all treated skin sites at the 1 and 24-hour observations with very slight to well-defined erythema at the 48 and 72-hour observations.
The reaction extended up to 4 cm bevond one treated skin site at the 24, 48 and 72-hour observations.
Very slight to slight oedema was noted at all treated skin sites at the 1-hour observation with very slight to moderate oedema at the 24 and 48-hour observations.
Slight oedema was noted at two treated skin sites at the 72-hour observation.
Desquamation was noted at two treated skin sites and crust formation, considered to be reversible, at one treated skin site at the 7-day observation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material, ISONOX 232, produced a primary irritation index of 3.5 and was classified as a MODERATE IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Regulation No. 1272/2008 (CLP).

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and very slight to slight oedema. Desquamation and crust formation were also noted.

The test material produced a primary irritation index of 3.5 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.