2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 Jul 1992

Deviations:

yes

Remarks:

The rabbits used in the study were slightly lighter and younger than proposed

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))

Version / remarks:

31 Jul 1992

Deviations:

yes

Remarks:

The rabbits used in the study were slightly lighter and younger than proposed

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Version / remarks:

1 Jul 1993

Deviations:

yes

Remarks:

The rabbits used in the study were slightly lighter and younger than proposed

Principles of method if other than guideline:

The rabbits used in the study were slightly lighter and younger than proposed in the protocol

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

EC Number:

419-740-4

EC Name:

2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Cas Number:

137658-79-8

Molecular formula:

C36 H45 N3 O4

IUPAC Name:

2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-{3-[(2-ethylhexyl)oxy]-2-hydroxypropoxy}phenol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: Z2651-01
- Expiration date of the lot/batch: Feb 1997
- Purity test date: ˃ 95%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (ca. 20°C) away from sunlight
- Stability under test conditions: stable at storage conditions
- Solubility and stability of the test substance in the solvent/vehicle (in bidistilled water): not specified; excluded from the Statement of Compliance

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was moistened with bidistilled water before application

OTHER SPECIFICS:
- pH: not assessed (insoluble in water)
- Description: yellowish solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

CRL:KBL(NZW)BR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Stolzenseeweg 32-36 0-88353 Kisslegg
- Age at study initiation: 10-12 weeks
- Weight at study initiation: males: 1,9 kg, females: 2 kg
- Weight at start of treatment: males: 2,1 kg, females: 2,1 kg
- Identification: By unique cage number and corresponding ear tags
- Housing: Individually in stainless steel cages with an automatic cleaning system, equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, Batch 89/95 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: Four days under test conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): humidity between 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark (light period between 6.00 a.m. to 6.00 p.m.), music during the light period.

IN-LIFE DATES:
Treatment May 15, 1995
Observation May 15 -18, 1995
Termination May 18, 1995

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/animal (left side only)

Duration of treatment / exposure:

4h

Observation period:

72h

Number of animals:

1 male, 2 female

Details on study design:

Before treatment:
Approximately 24 hours before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm X 10 cm). The skin of the animals was examined once, 1 day prior to test article administration. Only those animals with no signs of skin injury or irritation were used in the test.

TEST SITE
- Area of exposure: dorsal / back
- coverage: 6 m2
- Type of wrap if used: patch of surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was flushed with lukewarm tap water to clean the application site so that the reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4h

OBSERVATIONS
Viability/Mortality and Clinical Signs: Daily during the observation period.
Body Weights: At the start of acclimatization, on day 1 of test (application day) and at termination of observation.

SCORING SYSTEM:

The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test article.
The possible corrosive properties of the test article and the staining of the treated skin area related to the test article were described and recorded.

Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4
Maximum possible score 4

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

Maximum cumulative score: 8

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No corrosive effects were noted on the treated skin of any animal at any measuring

Any other information on results incl. tables

Table 1: Results skin irritation/skin corrosion: Mean values of the scores for each type of lesion, calculated for each animal separately

	Mean
Animal No.	Erythema	Edema
31, male	0.00	0.00
32, female	0.00	0.00
33, female	0.00	0.00

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results and on the referred classification criteria (according to EEC Commission Directive 93/21/EEC, April 27, 1993) the test substance is classified as "not irritating" to rabbit skin.

Executive summary:

The primary skin irritation potential of the test material was investigated by topical application of 0.5 g onto 6 cm2 intact dorsal skin of each of three young adult New Zealand rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) was used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then divided by the number of figures. Under the conditions of this experiment, the test substance was found to cause a primary irritation score of 0.00 (max. 8.0) when applied to healthy intact rabbit skin. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. The test article caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.