1-hydroxy-4-[[4-[(methylsulphonyl)oxy]phenyl]amino]anthraquinone

Endpoint summary

Description of key information

A maximisation study was performed to determine the contact allergenic potency of FAT 36038/F in albino guinea pigs according to OECD Guideline No. 406. Under the experimental conditions, 60 and 35 % of the animals of the test group showed skin reactions after removing the dressings at 24 and 48 hours, respectively. FAT 36038/F is therefore classified as skin sensitiser 1B.  

A supporting modified Beuhler study was performed to determine the possible allergenic potential of FAT 36038/G when administered to the skin of albino guinea pigs. In this study, 25 % of the test animals were observed with significant responses at either 24 or 48 hours when treated with the test article at 50 %. No significant responses were observed in the control group.Therefore, according to EEC (European Economic Community) classification criteria described in guidelines 93/21/EEC (EEC Official Journal Nr. L 110A, May 04, 1993) this test substance tested in concentration of 50 % in vaselinum album is considered to be a sensitizer.

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

Study period:

05 October, 1993 to 10 December, 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

Deviation from Standard Protocol: Due to technical reasons the acclimatisation period lasted 4 instead of 5 days.The challenge was performed during experimental week 4 (day 21) instead of week 5.

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:

Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.

Specific details on test material used for the study:

Test substance
Code number: FAT - 36038/F
En-Nr.: 409753.32
Purity 69.4 %
Appearance: solid
Storage: room temperature
Expiration date: 09/98

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, 4332 Stein / Switzerland
- Weight at study initiation: 307 to 387 g
- Housing: Macrolon cages (Type 3), housed individually
- Diet: NAFAG No. 845, Gossau SG, ad libitum
- Water: fresh water ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3 °C
- Humidity: 30 to 70 %

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

5 %

Day(s)/duration:

Day 0

Adequacy of induction:

highest technically applicable concentration used

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

50 %

Day(s)/duration:

Day 8

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

30 %

Day(s)/duration:

Day 21

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

The test was performed on 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group.

Details on study design:

PRETESTS
- Intradermal Induction
The concentration for the intradermal injections was selected on account of the solubility of the test article in standard vehicles and its local and systemic tolerability in a pretest. The following concentration of test article has been used for intradermal injection:
5 % in physiological saline (w/v).

- Epidermal Applications (induction and challenge)
The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. The following concentrations of FAT 36038/F have been examined on separate animals for the determination of the maximum sub-irritant concentration:
30 % and 50 % in Vaseline.
50 % in Vaseline was the highest applicable concentration of the test article.

TEST PROCEDURE
DAY 0: INDUCTION, intradermal injections
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the left and right side of the shaved neck of the test and control group animals.
*Test group:
- adjuvant/saline mixture 1:1 (v/v)
- 5 % FAT 36038/F in physiological saline (w/v)
- 5 % FAT 36038/F in the adjuvant/saline mixture (w/v)

*Control group:
- adjuvant/saline mixture 1:1 (v/v)
- adjuvant/saline mixture 1:1 (v/v)
- physiological saline

DAY 8: INDUCTION, epidermal application
The application site of all animals was pretreated with 10 % sodium-laurylsulfate (open application) 24 hours prior to the epidermal induction application. In the test group FAT 36038/F was incorporated in Vaseline (w/w) and applied on a filter paper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g per patch; occluded administration for 48 hours). The control group was treated with the vehicle only.
*Test group: 50 % FAT 36038/F in Vaseline
*Control group: Vaseline only

DAY 21: Challenge
The test and control group animals were tested on one flank with FAT 36038/F in Vaseline (w/w) and on the other flank wit the vehicle alone (patch 2x2 cm; approx. 0.2 g per patch; occluded administration for 24 hours).
*Test and control group:
- 30 % FAT 36038/F in Vaseline
- Vaseline only

Positive control substance(s):

yes

Remarks:

The sensitivity of the strain is checked once or twice a year with a known mild to moderate sensitiser, such as mercaptobenzothiazole, hexyl cinnamic aldehyde or potassiumdichromate.

Positive control results:

Reference value with 2-Mercaptobenzothiazole puriss. Test No 930012.
- Experimental starting date: July 5, 1993
- Experimental completion date: August 5, 1993

Concentrations of the reference compound and vehicles used:
*Intradermal induction
Concentration of compound: 5 %
Vehicle: Oleum arachis

*Epidermal induction
Concentration of compound: 50 %
Vehicle: vaseline

*Epidermal challenge
Concentration of compound: 30 %
Vehicle: vaseline

- Number of positive animals per group after occlusive epidermal application: 0/10 animal after 24 and 48 hours in the control group. In test group, 0/10 animal in vehicla control after 24 and 48 hours. In test article group 9/10 animals after 24 and 48 hours.
- Challenge reactions after epidermal application (control group): Score for erythema and edema is 0.0 (in males and females for the vehicle control and the test article control).
- Draize score 48 hours after removal of the dressing: Score for erythema and edema in vehicle control for male and female is 0.0. Score for erythema and edema for the test article control in male and female is 0.0.
- Challenge reactions after epidermal application (test group); Draize score 24 hours after removal of the dressing: Erythema and edema score is 0.0 in male and female for the vehicle contro group. For the test article group in males: 2 males have a score 1.0 and 2.0 and for edema 3 males scored with 1.0. In females 3 females have a score 1 and 2 females scored 2 for erythema parameter, for edema only 2 females are scored with 1.0.
- Challenge reactions after epidermal application (test group); Draize score 48 hours after removal of the dressing: Erythema and edema score is 0.0 in male and female for the vehicle contro group. For the test article group in males: 2 males have a score 1.0 and 2 other males with score 2.0 and for edema 1 male scored with 1.0. In females 3 females have a score 1 and 2 females scored 2 for erythema parameter, for edema only 1 female are scored with 1.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

vehicle only

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

challenge: 30 % FAT 36038/F in vaseline

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

vehicle only

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

challenge: 30 % FAT 36038/F in vaseline

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Intradermal induction: 5%, Epidermal induction: 50 % FAT 36038/F in vaseline and challenge: 30% FAT 36038/F

No. with + reactions:

12

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Intradermal induction: 5 %, Epidermal induction: 50 % FAT 36038/F in Vaseline and challenge: 30 % FAT 36038/F

No. with + reactions:

7

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Intradermal induction: 5 %, Epidermal induction: 50 % FAT 36038/F in Vaseline and challenge: Vaseline

No. with + reactions:

0

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Intradermal induction: 5 %, Epidermal induction: 50 % FAT 36038/F in Vaseline and challenge: Vaseline

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

Intradermal: 5 %, Epidermal: 50 % and Challenge: 30 % (2-Mercaptobenzothiazole puriss)

No. with + reactions:

9

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

Intradermal: 5 %, Epidermal: 50 % and Challenge: 30 % (2-Mercaptobenzothiazole puriss)

No. with + reactions:

9

Total no. in group:

10

Results in the pretest:

 

Intradermal induction: Since 5 % FAT 36038/F in physiological saline could be injected and was well tolerated, this concentration was used for the intradermal induction.

 

Epidermal application: Slight erythema reactions were observed with 50 % FAT 36038/F in vaseline in 1/2 animals at the 24 hours evaluation only.

 

RESULTS

Under the experimental conditions employed, 60 and 35 % of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings, respectively.

FAT 36038/F is, therefore, classified as a moderate sensitiser in albino guinea pigs according to the grading of Magnusson and Kligman.

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

FAT 36038/F is classified as a skin sensitiser 1B.

Executive summary:

A key study to determine the contact allergenic potency of FAT 36038/F test in albino guinea pigs was performed. This test was based on the OECD Guideline No. 406, adopted May 12, 1981, adapted July 17, 1992, by the OECD council, and on Annex V, Part B of Council Directive 67/548/EEC (Commission Directive 92/69/EEC of July 31, 1992). The test was performed on 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group, respectively. The doses used were 5 % FAT 36038/F in physiological saline for intradermal induction, 50 % FAT 36038/F in vaseline for epidermal induction and 30 % FAT 36038/F in vaseline for epidermal challenge. 60 % and 35 % of the animals of the test group showed skin reactions in the challenge after 24 and 48 hours, respectively. Hence, FAT 36038/F is classified as a skin sensitiser 1B.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Disperse Violet 57 was found to be sensitising in the available studies, hence needs to be classified as skin sensitiser 1B according to the Regulation (EC) No. 1272/2008.