reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 03rd 1989, August 03rd 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guideline and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

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:

-

EC Number:

406-040-9

EC Name:

-

Cas Number:

125643-61-0

Molecular formula:

C24-26 H40-44 O3

IUPAC Name:

C7-9-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate

Details on test material:

Physical properties: insoluble in water
Storage conditions: room temperature
Validity: May 1992
Test article received: May 18, 1989

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Animal strain as given in the report: Pirbright White Strain (Tif: DHP)
- Source: CIBA-GEIGY Limited, Tierfarm, 4332 Stein / Switzerland
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 336 to 446 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets - NAFAG No. 845, Gossau SG, ad libitum
- Water: fresh water, ad libitum
- Acclimation period:

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

All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer. Analytical results are available at the animal supply office. The drinking water is examined periodically by the IWB (Industrielle Werke Basel).

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

petrolatum

Induction 2

Concentration / amount:

The following concentrations have been examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration: 30 and 10 % in vaseline. Erythema reactions were observed with 30% in vaseline. 30% was, therefore, selected for the epidermal induction application and 10% as maximum subirritant concentration for the epidermal challenge application.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Challenge 2

Concentration / amount:

The following concentrations have been examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration: 30 and 10 % in vaseline. Erythema reactions were observed with 30% in vaseline. 30% was, therefore, selected for the epidermal induction application and 10% as maximum subirritant concentration for the epidermal challenge application.

No. of animals per dose:

10 male and 10 female guinea pigs per group

Details on study design:

The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
First Induction, intradermal application
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant/saline mixture 1:1 (v/v)
- test article in sesame oil (w/v)
- test article in the adjuvant saline mixture (w/v)
Second Induction, epidermal application
One week later the test article was incorporated in vaseline (w/w) and applied on a filterpaper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g paste per patch; occluded administration for 48 hours).

Challenge
Two weeks after the epidermal induction application the animals were tested on the flank with test material in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours).

Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings. The sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.

Observations and records
Induction reactions
After the intradermal and the epidermal induction application irritant reactions are normally induced by the adjuvant, the high test article concentration, or the sodium lauryl sulfate pretreatment. Because most of the reactions are treatment related and not compound related, the reactions are only described in special cases in the section of results.
Challenge reactions
Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings.

The sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.

Challenge controls:

A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test article (at least 10 animals) to check the maximum subirritant concentration of the test article in adjuvant treated animals.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

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: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

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: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information (EU 67/548/EEC and EC/1271/2008)

Conclusions:

In the GPMT, none of the guinea pigs of the test group showed skin reactions 24 and 48 hours after challenge with 10% test item.