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

Endpoint summary

Description of key information

To assess the allergenic potential of the test article in albino guinea pigs the Maximization-Test (OECD guideline 406) was conducted.

None of the animals of the test group were observed with positive skin reactions after treatment with a non-irritant test substance concentration of 50 % in PEG 400. No skin reactions were observed in the control group. Therefore the test article is considered to be a non-sensitizer when described under the test conditions.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

17 Jul 1992

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

LLNA method was not available yet by the time the study was conducted. Moreover, an appropriate guinea pig maximisation test is available which would not justify conducting an additional LLNA due to animal welfare.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: Z 2651-01
- Purity: > 95%
- Expiration date: Feb 1997

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container at room temperature (approx. 20°C), away from direct sunlight
- Stability under test conditions: Stable under storage condition
- Solubility and stability of the test substance in the solvent/vehicle: Unknown in PEG 400 and in a 1:1 (v/v) mixture of FCA/ physiological saline, is excluded from the statement of compliance

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

OTHER SPECIFICS:
- Description: Yellowish solid

Species:

guinea pig

Strain:

other: Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted) delivered by BRL

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Strain: Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted) delivered by BRL
- Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, 4414 Fullinsdorf/Switzerland
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 317 - 428 g
- Housing: Individually in Makrolon type-3 cages with autoclaved standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet (e.g. ad libitum): Pelleted standard Kliba 342, Batch no. 68/95 guinea pig breeding/maintenance diet ("Kliba", Klingentalmuhle AG, CH-4303 Kaiseraugst), ad libitum
- Water (e.g. ad libitum): Community tap water, ad libitum. Once weekly additional supply of ascorbic acid (1 g/l) via the drinking water
- Acclimation period: One week for the control and test group under test conditions after health examination. No acclimatization for the animals of the pretest. Only animals without any visual signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES:
Treatment / Observation: 22-MAY-1995 to termination
Termination: 15-JUN-1995

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Remarks:

The 1:1 mixture (v/v) of Freund's Complete Adjuvant:physiological saline was used as a vehicle for the intradermal induction in the main study.

Concentration / amount:

induction intradermal: 1% solution with PEG 400 and 1:1 mix with Freund`s solution
induction epidermal: 50% in PEG 400
injection of 0.1 ml/site

Day(s)/duration:

epidermal: 48 h

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Remarks:

The 1:1 mixture (v/v) of Freund's Complete Adjuvant:physiological saline was used as a vehicle for the intradermal induction in the main study.

Concentration / amount:

50 % in PEG 400

Day(s)/duration:

24 h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Control Group 10
Test Group 20
Intradermal Pretest 2
Epidermal Pretest 4

Details on study design:

RANGE FINDING TESTS:
performed during the acclimatization period to identify a maximally tolerated concentration of the test article suitable for the induction phase of the main study.
In addition, a suitable non-irritant concentration of the test article, by the topical route of administration, was identified for the challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three pairs of intradermal injections (0.1 ml/site) day 1, epidermal induction day 8
- Exposure period: epidermal 48 h
- Test groups: 20
- Control group: 10
- Frequency of applications: single
- Concentrations: see above

test area was pretreated with 10% Sodium-Lauryl-Sulfate (SLS) in paraffinum perliquidum as no primary irritation had been observed in the pretest

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 22
- Exposure period: 24 h
- Test groups: 20
- Control group: 10
- Concentrations: see above
- Evaluation (hr after challenge): after 24 and 48h, epilation cream used before

Scoring system:

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

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 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Challenge controls:

yes

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazol

Positive control results:

In this study 95% and 90% of the animals of the test group were observed with positive skin reactions at the 24- and 48-hour reading respectively after treatment with a non-irritant test substance concentration of 5% in peanut oil.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Remarks:

A slight yellow discolouration was noted after removal of the dressing

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Remarks:

A slight yellow discolouration was noted after removal of the dressing

- No toxic symptoms were evident in the guinea pigs of the control or test group

- No deaths occurred in the control and test groups

Interpretation of results:

GHS criteria not met

Conclusions:

In this study (according OECD guideline 406) none of the animals of the test group were observed with positive skin reactions after treatment with a non-irritant test substance concentration of 50% in PEG 400. No skin reactions were observed in the control group. Therefore, the test article at a concentration of 50 % in PEG 400 is considered to be a non-sensitizer when described under the test conditions.

Executive summary:

To assess the allergenic potential of the test article in albino guinea pigs the Maximization-Test according to a GLP-compliant OECD guideline 406 was used. Ten females were used as control group and 20 females were used as test group. The highest non-irritating test article concentration used for challenge application was 50 % in PEG 400.

None of the animals showed any treatment related skin reactions. Neither toxic symptoms nor deaths occurred in the control and test groups.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

To assess the allergenic potential of the test article in albino guinea pigs the Maximization-Test (OECD guideline 406) was conducted. Ten female animals were used as control group and 20 females were used as test group. After intradermal and epicutaneously induction, the animals were challenged epicutaneous with a 50 % solution of the substance in PEG 400. Evaluation and scoring of the reactions followed after 24h and 48h. Positive controls were performed with 2 -Mercaptobenzothiazol.

None of the animals showed erythema or oedema after treatment with the test article. Neither toxic symptoms nor deaths occurred in the control and test groups.

Multiple application of the test substance onto skin did not cause an allergic reaction. Therefore, the test substance is considered to be a non-sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Sensitisation after inhalation of the test substance was not investigated. The major part of the substance has a particle size of > 40µm (92 %) or more. Inhalable particles of < 10 or < 4 µm are not included. As the substance has a very low vapour pressure, inhalation exposure is not relevant.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No local reactions were observed in a guinea pig maximization test (OECD 406) after induction. Therefore, the substance does not require classification as a skin sensitizer under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.