A mixture of: α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-hydroxypoly(oxyethylene); α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyloxypoly(oxyethylene)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Jul. 18, 1984 to Sep. 25, 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The guideline study was conducted according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-hydroxypoly(oxyethylene); α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyloxypoly(oxyethylene)

EC Number:

400-830-7

EC Name:

A mixture of: α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-hydroxypoly(oxyethylene); α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyloxypoly(oxyethylene)

Cas Number:

104810-48-2

IUPAC Name:

14-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)-3,6,9,12-tetraoxatetradecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 14-hydroxy-3,6,9,12-tetraoxatetradecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; tris(17-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)-3,6,9,12,15-pentaoxaheptadecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate); tris(17-hydroxy-3,6,9,12,15-pentaoxaheptadecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate); 2-(2-hydroxyethoxy)ethan-1-ol; 2-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)ethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 2-[2-(2-hydroxyethoxy)ethoxy]ethan-1-ol; 2-[2-(2-hydroxyethoxy)ethoxy]ethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 2-hydroxyethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 2-methoxyethan-1-ol; 2-{2-[2-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)ethoxy]ethoxy}ethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 20-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)-3,6,9,12,15,18-hexaoxaicosan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 20-hydroxy-3,6,9,12,15,18-hexaoxaicosan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 3,6,9,12,15,18,21-heptaoxatricosane-1,23-diol; 3,6,9,12,15-pentaoxaheptadecane-1,17-diol; 3,6,9,12-tetraoxatetradecane-1,14-diol; bis(ethane-1,2-diol)

Details on test material:

- Physical state: liquid
- Lot/batch No.: Batch No. B
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Strain as stated in the report: Pirbright White (Tif:DHP)
- Source: Bred on the premises (Toxicology, CIBA-GEIGY AG, Basel Switzerland)
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 302 to 410 g
- Housing: individually in Macrolon cages (Type 3)
- Diet ad libitum: standard guinea pig pellets NAFAG No. 846 supplemented with fresh carrots
- Water ad libitum: fresh water
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 50 ± 10
- Photoperiod (hrs dark / hrs light): 10/14
(14-hour light cycle was necessary to eliminate seasonal variation since the animal rooms were not totally protected from natural sunlight).

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: The test article was diluted in sesame oil (intradermal application) or vaseline (epidermal application)

Induction 2

Concentration / amount:

The intradermal induction was performed with 1% test article in sesame oil and Freund Complete Adjuvant (FCA)/Saline mixture, respectively.
The epidermal induction was conducted with 10% test article in Vaseline and an amount of 0.4 g.
The epidermal challenge was performed with 1% test article in Vaseline.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: The test article was diluted in sesame oil (intradermal application) or vaseline (epidermal application)

Challenge 2

Concentration / amount:

The intradermal induction was performed with 1% test article in sesame oil and Freund Complete Adjuvant (FCA)/Saline mixture, respectively.
The epidermal induction was conducted with 10% test article in Vaseline and an amount of 0.4 g.
The epidermal challenge was performed with 1% test article in Vaseline.

No. of animals per dose:

10 males, 10 females

Details on study design:

RANGE FINDING STUDY
The concentrations of test article for induction and challenge periods were determined on separate animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2; one intradermal injection (0.1 ml/site) of 1% test article in sesame oil and one epidermal application of 10% test article in Vaseline (0.4 g) for 48 h one week later (see below).
- Test groups: 10 males, 10 females
- Control groups: 10 males, 10 females
- Site: Following intrademal injections (0.1 ml per injection) were made into the neck of the guinea pigs: adjuvant/saline mixture, test article in sesame oil, test article in adjuvant/saline mixture.

SECOND INDUCTION WEEK, EPIDERMAL APPLICATION
In the second week of induction the test article was incorporated into vaseline (10%) and applied under occlusive conditions to the neck of the animals for 48 hours.
- Test groups: 10 males, 10 females
- Control groups 10 males, 10 females
- Site: neck

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: animals were tested two weeks after the epidermal induction application.
- Exposure period: 24 h
- Test groups: 10 males, 10 females, animals were tested on the flank with 1% test article in vaseline or the vehicle alone
- Control group: 10 males, 10 females, were treated with the vehicle as well as with the test compound to control the maximal subirritant concentration of the test compound in adjuvant-treated animals.
- Site: flank
- Concentrations: 1% in vaseline (occlusive epidermal challenge)
- Evaluation (h after challenge): 24 and 48 h

CHALLENGE REACTIONS: 24 and 48 h after removing the dressings, the challenge reactions were graded according to the Draize scoring scale (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO)).

SCORING SYSTEM
24 and 48 h after removing the dressings, the challenge reactions were graded according to the Draize scoring scale.

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

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

Challenge controls:

During the challenge period, the animals were treated with the vehicle as well as with the test compound to control the maximal subirritant concentration of the test compound in adjuvant-treated animals.

Positive control substance(s):

yes

Remarks:

p-phenylenediamine

Study design: in vivo (LLNA)

Details on study design:

Not applicable.

Statistics:

Statistical analysis was not performed.

Results and discussion

Positive control results:

The sensitivity of the strain is tested every six months with p-phenylenediamine.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

14

Total no. in group:

20

Clinical observations:

Erythema and edema were seen in 14 and 10 of 20 animals (all graded 1), respectively.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 14.0. Total no. in groups: 20.0. Clinical observations: Erythema and edema were seen in 14 and 10 of 20 animals (all graded 1), respectively..

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

10

Total no. in group:

20

Clinical observations:

Edema were seen in 10 of 20 animals (graded 1).

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 10.0. Total no. in groups: 20.0. Clinical observations: Edema were seen in 10 of 20 animals (graded 1)..

Any other information on results incl. tables

Table 1: Details on skin reactions after challenge procedure.

Reading time point	24 h			48 h
	positive	total	% positive of total	positive	total	% positive of total
Challenged with:	Control group (induced without test article)
Test article	0	20	0	0	20	0
Vehicle	0	20	0	0	20	0
	Test group (induced with test article)
Test article	14	20	70	10	20	50
Vehicle	0	20	0	0	20	0

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance fulfills the criteria for EU GHS sensitization category 1A.