5-(benzoylamino)-4-hydroxy-3-[[1-sulpho-6-[[2-(sulphooxy)ethyl]sulphonyl]-2-naphthyl]azo]naphthalene-2,7-disulphonic acid, sodium salt

Endpoint summary

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:

September/October 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG
- Weight at study initiation: mean 295 g; range: 265 g to 337 g; n = 15
- Housing: group-housing (5/cage)
- Diet: Altromin 3112 for guinea pigs and rabbits ad libitum
- Water: tap water ad libitum
- Acclimation period: at 1east 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 35 to 75%
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: September 22 to October 23, 1992

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Concentration / amount:

Intradermal: 5%
dermal induction: 25%
dermal challenge: 2.5%

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

Intradermal: 5%
dermal induction: 25%
dermal challenge: 2.5%

No. of animals per dose:

Determination of primary not irritating concentration: 6
Determination of intradermal tolerability: 3
Sentinel group: 5
Control group: 5
Treatment group: 10

Details on study design:

RANGE FINDING TESTS:

Determination of the primary non-irritant concentration:
In a dermal-occlusive test for primary skin irritation, each of the following test concentrations was applied to the left flank of two guinea pigs:
25.0 %Remazol-Brillantrot F3B in isotonic saline
5.0 %Remazol-Brillantrot F3B in isotonic saline
1.0 % Remazol-Brillantrot F3B in isotonic saline
The hair on the left flanks of the animals was removed mechanically. 0.5 mL of the test substance preparation was applied to a 2 x 2 cm cellulose patch, which was then fixed to the left flank and covered occlusively for 24 hours with a bandage and film. 24 hours after removal of the patches, the treated skin areas were examined for erythema and oedema

Determination of the tolerance of intradermal injections:
To determine the tolerance of intradermal injections, each of the following preparations (5.0%, 1.0%, 0.2% in isotonic saline) was administered twice by intradermal injection to 3 guinea pigs. The injection sites (sites 1, 2 and 3) were all within a dorsal area measuring 2 x 4 cm in the vicinity of the shoulder.


MAIN STUDY
A. INTRADERMAL INDUCTION
- No of Injections: 2 x 3 preparations: 50% FCA, 5% TS in 0.9% NaCl, 5% TS in 50% FCA - treatment group
50% FCA, 0.9% NaCl, 50% FCA - control and attending group
- Exposure period: Injection on Day 1, observation Day 1 to Day 7
- Site: shoulder

B. DERMAL INDUCTION EXPOSURE
- No. of exposures: one
- Exposure period: 48 hours
- Test groups: 25% TS in 0.9% NaCl
- Control group: 0.9% NaCl
- Site: shoulder
- Frequency of applications: single
- Duration: Day 8 to Day 22
- Concentrations: 25%

C. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22 (15 for attending group)
- Exposure period: 24 hours
- Test groups: 2.5% TS + 0.9% NaCl
- Control group: 2.5% TS + 0.9% NaCl
- Site: right flank: TS; left flank: 0.9% NaCl
- Concentrations: 2.5%
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:

In addition to the control group, 5 further guinea pigs (attending group) were used to confirm that challenge exposure with 2.5% TS would not lead to dermal irritation in animals pre-treated with 50% FCA.

Positive control substance(s):

yes

Remarks:

bi-annually tested

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 2.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Induction treatment

The treated animals showed no clinical signs of intoxication throughout the study.

The intradermal injections with Freund's Adjuvant caused severe erythema and oedema, indurat ions and encrustations (evaluaton of erythema formation was not possible at the sites treated with the test substance due to red discolourations).

The application sites treated with the test substance showed very slight oedema and encrustations, evaluation of erythema formation was not possible. Injections of the vehicle alone did not cause any sign of irritation.

Due to these strong irritation reactions of the skin, 10% sodium dodecylsulfate was not applied at day 7.

After the removal of the patch at day 10, erythema as well as oedema, indurated and encrusted skin and necrosis were observed at the sites previously treated with Freund's Adjuvant. The application sites treated with the test substance in vehicle showed very light oedema, indurations and encrustations (evaluation of erythema formation was not possible at the sites treated with the test substance

due to dark red discolourations). No signs of irritations occurred at the sites treated with the vehicle alone. The app1ication sites of the treatment group were discoloured dark red. The body weight gains of the treated animals were not impaired.

Challenge treatment

No signs of irritation were observed in the control and treatment group 24 and 48 hours after removal of the occlusive bandage. The skin surface of all animals was discoloured light red.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is not sensitizing in pirbright white guinea pigs.

Executive summary:

Testing for sensitizing properties was performed in female Guinea pigs according to the method of MAGNUSSON & KLIGMAN.

Intradermal induction was performed using 5% test substance in isotonic saline. Dermal induction was carried out with 25% test substance in isotonic saline. Challenge treatment was performed using 2.5% test substance in isotonic saline.

Based on the results of this study Reactive Red 180 showed no evidence for sensitizing properties.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Testing for sensitizing properties was performed in female Guinea pigs according to the method of MAGNUSSON &KLIGMAN.

Intradermal induction was performed using 5% test substance in isotonic saline. Dermal induction was carried out with 25% test substance in isotonic saline. Challenge treatment was performed using 2.5% test substance in isotonic saline.

Based on the results of this study Reactive Red 180 showed no evidence for sensitizing properties.

Migrated from Short description of key information:
Reactive Red 180 showed no evidence for sensitizing properties.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

The registered chemical is a reactive dye. For this class of dyes it was generally agreed between the members of the Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers (ETAD) that a possible risk for respiratory sensitisation for workers exists at high exposure. However the following should be noted: 

1) For the substance no history of respiratory problems, such as occupational asthma, is associated with the manufacture and use of the specific substance.

2) Due to the granular form of the substance (spray dried in closed system from aqueous solution directly after synthesis) or the properly de-dusted powder no risk for inhalative exposure arises.

The potential to cause respiratory sensitisation is therefore not considered to be applicable for this substance.

No evidence of respiratory sensitisation was noted in any of the studies conducted, and it is proposed that the substance is not a respiratory sensitiser.

Migrated from Short description of key information:
Not assessed. No evidence of respiratory sensitisation was noted in any of the studies conducted, and it is proposed that the substance is not a respiratory sensitiser.

Justification for classification or non-classification

The skin sensitisation study in the guinea pig using the Magnusson & Kligman Method has been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the study was conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for sensitisation is therefore required.