Diisopropyl 3,3'-[(2,5-dichloro-1,4-phenylene)bis[iminocarbonyl(2-hydroxy-3,1-naphthylene)azo]]bis[4-methylbenzoate]

Endpoint summary

Description of key information

Pigment Red 221 did not cause skin sensitization in the guinea pig maximization test (OECD 406) (Ciba-Geigy 1986).

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted 1981

Deviations:

yes

Remarks:

no details on the composition of the adjuvant mixture; exact guideline was not mentioned ("..study was carried out as recommended in the OECD guidelines 1981...."); diet supplementation with ascorbic acid is equivocal; no details on the pilot/range finder

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

When the GPMT was performed in 1985, the LLNA did not yet exist as an OECD Testing guideline.

Specific details on test material used for the study:

- Physical state: powder
- Analytical purity: commercial grade
- Batch No.: EN 94903.52
- Storage condition of test material: room temperature

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: in-house breeding
- Age at study initiation: about 10 weeks
- Weight at study initiation: 303-426 g
- Housing: individually
- Diet (ad libitum): standard guinea pigs pellets - NAFAG No. 846, Gossau SG
- Water (ad libitum): fresh water, supplemented with fresh carrots
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

other: sesame oil (intradermal induction), vaseline (epicutaneous application)

Concentration / amount:

intradermal induction: 1%
epicutaneous induction: 30% (about 0.4 g/patch)
challenge: 10% (about 0.2 g/patch)

Route:

epicutaneous, occlusive

Vehicle:

other: sesame oil (intradermal induction), vaseline (epicutaneous application)

Concentration / amount:

intradermal induction: 1%
epicutaneous induction: 30% (about 0.4 g/patch)
challenge: 10% (about 0.2 g/patch)

No. of animals per dose:

10 males and 10 females

Details on study design:

RANGE FINDING TESTS: The concentrations of the test compound for induction and challenge periods were determined on separate animals (no further information).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal exposure (Day 1) and 1 epicutaneous exposure (one week later)
- Exposure period: Day 1: 2 intradermal injections; Readings: 24 hours after the beginning of application. After one week: 48 hours epicutaneous exposure.
- Test groups: Intradermal: Each two injections: A) front row: 0.1 ml mixture adjuvant and saline; B) middle row : 0.1 ml of the test substance formulation in sesame oil; C) back row : 0.1 ml of the test substance formulation in the adjuvant saline mixture
Epicutaneous: about 0.4 g of the test substance incorporated in vaseline under an occlusive dressing, duration of exposure 48 hours; Readings 48 hours after the beginning of application. The application sites were pretreated the day before with 10% sodium lauryl sulfate (open application).
- Control group: Intradermal: same injections (A, B, C) but without test substance. Epicutaneous: Animals were treated analogously to the test group, but only with the solvent.
- Site: neck
- Frequency of applications: 2 intradermal injections and 1 epicutaneous exposure (see above)
- Duration: Day 1 (intradermal injection) – after one week (epicutaneous exposure)
- Concentrations: 1 % of the test substance with intradermal induction; 30 % of the test substance with epicutaneous application

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 days after intradermal injection
- Exposure period: 24 hours
- Test groups: about 0.2 g of the test substance (flank) under an occlusive dressing.
- Control group: 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 (no further information).
- Site: flank (the application sites where chemically depilated 3 hours before examination (Veet, about 5 minutes))
- Concentrations: 10 % of the test substance
- Evaluation (hr after challenge): 24, 48 hours after removal of the patch

OTHER: The test was carried out according to the maximization test of Magnusson and Kligman (J. invest. Dermatol. 52, 268-276, 1969).

Positive control substance(s):

yes

Remarks:

p - phenylenediamine

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

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.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

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.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.

After occlusive epicutaneous administration, no skin reactions were found in the control and test groups.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Pigment Red 221 (CAS 71566-54-6, 926 g/mol)

Pigment Red 221 was tested in a GLP compliant guinea pig maximization test following OECD testing guideline 406 (Ciba-Geigy Ltd 1986a). A concentration of 1% was used for intradermal application in a sesame oil and saline adjuvant mixture. 30% was used for epidermal application (Induction) in vaseline. For challenge exposure, 10% in vaseline was applied. The test was performed on 10 male and 10 female guinea pigs per group. At the concentration of 10% in vaseline, Pigment Red 221 did neither induce edema nor erythema reactions after epidermal challenge application and was therefore found to be non skin sensitizing.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

 Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.