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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:
June 27th, 1988 to July 29th, 1988
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 293 g; range: 241 g to 338 g; n = 15
- Housing: group-housing (5/cage)
- Diet: Altromin ERKA-Mischfutter Nr. 8300 for guinea pigs and rabbits ad libitum
- Water: tap water ad libitum
- Acclimation period: ca. 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: June 27th, 1988 to July 29th, 1988
Route:
intradermal and epicutaneous
Vehicle:
other: intradernal: saline; epicutaneous: vaseline
Concentration / amount:
Intradermal: 5%
dermal induction: 25%
dermal challenge: 2.5%
Route:
epicutaneous, occlusive
Vehicle:
other: intradernal: saline; epicutaneous: vaseline
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-Goldgelb RNL in vaseline
2.5 % Remazol-Goldgelb RNL in vaseline
0.25 % Remazol-Goldgelb RNL in vaseline
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%, 0.25% 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: 25% TS + 0.9% NaCl
- Control group: 25% TS + 0.9% NaCl
- Site: right flank: TS; left flank: 0.9% NaCl
- Concentrations: 25%
- 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:
10
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: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
10
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: 10.0. Total no. in groups: 10.0.
Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item is sensitizing in pirbright white guinea pigs.

Classification: sensitizing
Executive summary:

Testing for sensitizing properties of Remazol Gelb RLN 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 and challenge treatment were carried out with 25% and 2.5% test substance in white vaseline.

Based on the results of this study Remazol Gelb RLN showed evidence for sensitizing properties.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Testing for sensitizing properties of Remazol Gelb RLN 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 and challenge treatment were carried out with 25% and 2.5% test substance in white vaseline.

Based on the results of this study Remazol Gelb RLN showed evidence for sensitizing properties.


Migrated from Short description of key information:
Reactive Orange 107 showed evidence for skin sensitizing properties

Respiratory sensitisation

Endpoint conclusion
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.

CLP Regulation (EC No 1272/2008): Skin Sensitiser 1B – H317

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