2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-08-11 - 1992-11-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The GPMT has been carried out as an animal test to predict human sensitisation for over a decade and is recommended by international test guidelines such as OECD.

Test material

Test material information

Constituent 1

Reference substance name:

2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol

EC Number:

411-380-6

EC Name:

2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol

Cas Number:

147315-50-2

Molecular formula:

C27 H27 N3 O2

IUPAC Name:

2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-(hexyloxy)phenol

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pirbright White Strain (Tif: DHP)

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production, Stein, Switzerland
- Age at study initiation: young adult based on body weight range
- Weight at study initiation: 334 to 414 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 1992-09-07 To: 1992-10-08

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

petrolatum

Induction 2

Concentration / amount:

Intradermal induction exposure: 5%
Epicutaneous induction and epicutaneous challenge exposure (based on pretest results): 40%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Challenge 2

Concentration / amount:

Intradermal induction exposure: 5%
Epicutaneous induction and epicutaneous challenge exposure (based on pretest results): 40%

No. of animals per dose:

Pretest: 6 animals (3 males, 3 females)
Main test: 20 test animals (10 males, 10 females), 10 control animals (5 males, 5 females),

Details on study design:

RANGE FINDING TESTS:
A pretest was performed to identify appropriate test item concentrations for induction and challenge in the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 exposures, i.e. a single intradermal exposure in week 1 (6 injections/animal) and an epicutaneous exposure in week 2 (closed patch)
- Exposure period: single application (intradermal exposure), 48 hours (epicutaneous exposure)
- Test group: 1 group of 20 animals
- Control group: 1 group of 10 animals
- Site: neck region
- Frequency of applications: 1 intradermal application (week 1) and 1 epicutaneous application (week 2)
- Concentrations: 5 % (intradermal exposure), 40 % (epicutaneous exposure)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 epicutaneous exposure
- Day of challenge: in week 5 of the study period
- Exposure period: 24 hours
- Test group: 1 group of 20 animals
- Control group: 1 group of 10 animals
- Site: neck region
- Concentration: 40 % (epicutaneous exposure)
- Evaluation: approximately 24 and 48 hours after removal of the dressing

OTHER:
No skin irritation was observed in the pretest. Therefore the application site was pretreated with 10 % sodium laurylsulfate (open application) 24 hours prior to the epidermal induction application.

Challenge controls:

No evident positive reactions were noted after the first challenge application, neither when treated with vaseline alone nor when treated with a 40% test substance dilution.

Positive control substance(s):

yes

Remarks:

Potassiumdichromate, for the induction period a 0.20 % dilution in physiological saline (intradermal induction) and 5 % preparation in vaseline (for epidermal induction) was used. For the challenge procedure a 1 % preparation in vaseline was used.

Results and discussion

Positive control results:

A positive control with a known sensitizer produced the expected rate of sensitization reactions and demonstrated the sensitivity of the test system.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

40%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

40%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

40 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

40 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

In a dermal sensitisation study with the test item (as described in section 1.2) in Oleum arachidis (intradermal induction) or in vaseline (epicutaneous applications), young adult guinea pigs (test group: 10 males and 10 females, control group: 5 males and 5 females) were tested using the guinea pig maximisation test of Magnusson and Kligman. In this study, the test group animals received 5 % of the test item for intradermal induction in week 1 as well as 40 % (highest non-irritant concentration) of the test item for epicutaneous induction in week 2 and challenge in week 5. Concurrent negative control animals were treated similarly, except that during the induction phase the test item was omitted. No animal of the test group was sensitised by the test item under the experimental condition employed. Under the conditions of this study, the test item was not a skin sensitiser.