Trisodium 5-[[4-chloro-6-(methylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

None

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The optimization test similar to the method recommended in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (19 59), the US Association of Food and Drug Officials (AFDO).

Deviations:

not specified

Principles of method if other than guideline:

None

GLP compliance:

no

Type of study:

Maurer optimisation test

Justification for non-LLNA method:

None

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium 5-[[4-chloro-6-(methylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

EC Number:

274-417-3

EC Name:

Trisodium 5-[[4-chloro-6-(methylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Cas Number:

70210-20-7

Molecular formula:

C26H20ClN7O10S3.3Na

IUPAC Name:

trisodium 5-[[4-chloro-6-(methylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Test material form:

not specified

Specific details on test material used for the study:

None

In vivo test system

Test animals

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Animals:
The test was performed on groups of 10 male and 10 female guinea pigs of the Pirbright white strain bred on the premises and weighing between 350 to 400 grams. The animals were housed individually in Macrolon cages, type 3, kept at a constant room temperature of 22 +/- 1° C, at a relative humidity of 55 + 5 % and on a 14 hours light cycle day. The animals received ad libitum standard guinea pig pellets - NAFAG, No. 830, Gossau SG - supplemented with fresh carrots.

Study design: in vivo (non-LLNA)

Induction

Route:

other: intracutaneous injections

Vehicle:

other: physiological saline

Concentration / amount:

0.1 % solution of FAT 40034/B in physiological saline

Challenge

Challenge 1

Route:

intradermal

Vehicle:

other: physiological saline

Concentration / amount:

0.1 % solution of FAT 40034/B in physiological saline

Challenge 2

No.:

#2

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

3%

Adequacy of challenge:

other: sub irritant concentration

No. of animals per dose:

The test was performed on groups of 10 male and 10 female guinea pigs.

Details on study design:

Testing procedure:
During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % solution of FAT 40034/B in physiological saline. One control group was treated with the vehicle alone ("negative control").
On the first day, injections of 0.1 ml were administered into the shaven skin of the right flank and the back, while on the following days a single intracutaneous injection was given into the back.
During the second and third week of the induction period the test material was incorporated in a mixture of the normal vehicle with complete Bacto Adjuvant2:

(vehicle : adjuvant = 1 : 1).

Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % solution of FAT 40034/B in physiological saline was administered into the skin of the left flank.
Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded.

The two largest perpendicular diameters (in mm) and the increase in the skin- fold thickness (in mm) were measured and by multiplication of these values "reaction volume' was obtained (in ul) for each reading from each animal.
The mean volume plus one standard deviation of the induction reactions observed in the individual animal in the first week was taken as representing the skin irritation "threshold" for each animal. Any challenge reaction greater than this threshold value in the induction period was graded as an allergic reaction and the animal termed "positive". The number of "positive" animals in the test group was compared with the number of animals in the control group (treated with the vehicle alone) that showed a non-specific reaction of at least the same magnitude ("negative control").

Ten days after the intracutaneous challenge injection a subirritant dose of the test compound was applied epicutaneously under occlusive dressings which were left in place for 24 hours.

Challenge controls:

None

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

3%

No. with + reactions:

13

Total no. in group:

20

Clinical observations:

Erythema observed in 13 animals out of 20

Remarks on result:

other: Incidence of positive animals per group after occlusive epicutaneous application

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

20

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40034/B is considered to be skin sensitizing (contact allergenic) in albino guinea-pigs.

Executive summary:

A study was performed to determine the sensitization of FAT 40034 in albino guinea pigs according to "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO). During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % solution of FAT 40034/B in physiological saline. One control group was treated with the vehicle alone. Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded. Intradermal injection of the vehicle alone failed to induce sensitization. Under the experimental conditions employed, significant differences between the test group and the vehicle-treated controls were seen after both intradermal and epidermal challenge application of FAT 40034/B. FAT 40034/B is therefore considered to possess skin sensitizing (contact allergenic) potential in albino guinea- pigs.