Registration Dossier

Administrative data

Description of key information

Reactive Red 65 is classified as a strong sensitizer in albino guinea pigs.

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:
November 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
May 12, 1981
Deviations:
not specified
Qualifier:
according to
Guideline:
other: EEC directive 79/83
GLP compliance:
no
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:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: EN 80158.32
- Expiration date of the lot/batch: April 1990

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under storage conditions: guaranteed by the sponsor
Species:
guinea pig
Strain:
Pirbright-Hartley
Remarks:
Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: In-house breeding
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 328 - 439 g
- Housing: The animals were housed individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets - NAFAG No.846, Gossau SG ad libitum
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12 h light cycle day

IN-LIFE DATES: From: 15-10-1985 To: 25-11-1985
Route:
intradermal
Vehicle:
other: Intradermal application: Test compound FAT 40062/B in physiological saline Test compound FAT 40062/B in the adjuvant saline mixture Adjuvant and saline mixture (1:1) Epidermal application: Vaseline
Concentration / amount:
1 % / 0.1 ml
Day(s)/duration:
Day 1
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
10 % / 0.4 g in vaseline
Day(s)/duration:
Day 8
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
0.3% / 0.2 g
Day(s)/duration:
Two weeks after the epidermal induction
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 males and 10 females
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (Intradermal and Epidermal)
- Exposure period: Intradermal : 1 week and Epidermal: 48 h
- Test groups: 1
- Site: neck of the animals
- Frequency of applications:
- Duration: 48 h
- Concentrations: 0.4 g paste of 10 % test substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 48 h (2 days)
- Exposure period: 24 h
- Test groups: 10 males and 10 females
- Control group: yes
- Site: flank
- Concentrations: 0.2 g paste of 0.3 % test substance in vaseline
- Evaluation (h after challenge): 48 h
Challenge controls:
A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test compound (at least 10 animals) to control the maximal subirritant concentration of the test compound in adjuvant treated animals.
Positive control substance(s):
no
Positive control results:
Not applicable
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.2 g of 0.3 % test substance
No. with + reactions:
18
Total no. in group:
19
Clinical observations:
Erythema, Edema, body weight
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.2 g of 0.3 % test substance
No. with + reactions:
9
Total no. in group:
19
Clinical observations:
Erythema, edema
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1 ml
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1 ml
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not measured/tested

DRAIZE Score 24 hours after removal of the dressings: Test Compound

Male animals

341

342

343

344

345

346

347

348

349

350

Erythema Score

1

+

1

1

1

1

1

1

1

1

Edema Score

0

0

0

0

1

0

0

1

0

0

 

Female animals

351

352

353

354

355

356

357

358

359

360

Erythema Score

1

1

1

1

1

1

0

1

1

1

Edema Score

0

1

0

0

0

0

0

0

1

1

DRAIZE Score 24 hours after removal of the dressings: Control

Male animals

341

342

343

344

345

346

347

348

349

350

Erythema Score

0

+

0

0

0

0

0

0

0

0

Edema Score

0

 

0

0

0

0

0

0

0

0

 

Female animals

351

352

353

354

355

356

357

358

359

360

Erythema Score

0

0

0

0

0

0

0

0

0

0

Edema Score

0

0

0

0

0

0

0

0

0

0

DRAIZE Score 48 h after removal of the dressings: Test Compound

Male animals

341

342

343

344

345

346

347

348

349

350

Erythema Score

0

+

0

0

1

1

0

1

0

0

Edema Score

0

0

0

0

0

0

0

0

0

0

 

Female animals

351

352

353

354

355

356

357

358

359

360

Erythema Score

0

1

0

1s

1

0

0

0

1

1

Edema Score

0

0

0

0

0

0

0

0

1

1

DRAIZE Score 48 h after removal of the dressings: Control

Male animals

341

342

343

344

345

346

347

348

349

350

Erythema Score

0

+

0

0

0

0

0

0

0

0

Edema Score

0

 

0

0

0

0

0

0

0

0

 

Female animals

351

352

353

354

355

356

357

358

359

360

Erythema Score

0

0

0

0

0

0

0

0

0

0

Edema Score

0

0

0

0

0

0

0

0

0

0

 

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
FAT 40062/B showed a moderate to strong grade of skin-sensitizing (contact allergenic) potential in albino guinea pigs.
Executive summary:

A GPMT test was performed to determine the contact allergenic potency of FAT 40062/B in albino guinea pigs. The test was carried out according to the maximization test of Magnusson and Kligman (J. invest. Dermatol. 52, 268-276, 1969, Cont. Dermatitis 6, 46-50, 1980), recommended in the OECD guideline 406, adopted May 12, 1981 and in the EEC directive 79/83 The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later. Two weeks after the epidermal induction application the animals were tested on the flank with FAT 40062/B in vaseline and the vehicle alone (patch 2 x 2 cm; occluded administration for 24 h). The incidence of positive animals per group and the individual challenge reactions and the individual animal weights at start and end of the test are observed and recorded. Under the experimental conditions employed, 45-95 % of the animals of the test group showed skin reactions 24 and 48 h after removing the dressings. After 24 h challenge 9/sex rabbits showed erythema while 2 male and 3 female showed edema. However, after 48 h challenge 3 male and 5 female rabbit showed erythema while 2 female rabbit showed edema. Animal No.342 died during the rest period between induction and challenge. The death of the animal was unrelated to the test compound application. There were no adverse effects were seen on body weight. FAT 40062/B is therefore classified as a strong sensitizer in albino guinea pigs according to the grading of Magnusson and Kligman.

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

A GPMT test was performed to determine the contact allergenic potency of FAT 40062/B in albino guinea pigs. The test was carried out according OECD guideline 406. The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later. Two weeks after the epidermal induction application the animals were tested on the flank with FAT 40062/B in vaseline and the vehicle alone (patch 2 x 2 cm; occluded administration for 24 h).

After 24 h challenge 9/sex rabbit showed erythema while 2 male and 3 female showed edema. However, after 48 h challenge 3 male and 5 female rabbit showed erythema while 2 female rabbit showed edema. Animal No.342 died during the rest period between induction and challenge. The death of the animal was unrelated to the test compound application. There were no adverse effects were seen on body weight.

FAT 40062/B is therefore classified as a strong sensitizer in albino guinea pigs according to the grading of Magnusson and Kligman.

Respiratory sensitisation

Link to relevant study records
Reference
Endpoint:
respiratory sensitisation
Type of information:
other: 3rd party hazard and risk assessment
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from Handbook or collection of data
Qualifier:
no guideline available
Principles of method if other than guideline:
Data from Handbook or collection of data.
GLP compliance:
no

ETAD guidance - Labelling of reactive dyes

 

Respiratory sensitization potential of some Reactive dyes:

Appropriate MSDS information and hazard labelling

 

ETAD has addressed the concerns that a small percentage of reactive dyes have caused respiratory sensitisation. Based on available knowledge, the possibility that other reactive dyes may also cause respiratory sensitisation cannot be excluded. Because there is at present no suitable animal test system for respiratory sensitisation, ETAD recommends the following:

 

For all Reactive dyes

 

1.    Safety data sheet

 

Information should be given of the possible respiratory sensitisation effects of reactive dyes of all classes. It is the responsibility of each company to determine how this information should be given in accordance with the regulatory requirements in the various countries.

 

2.    Labelling

 

Good working practice requires that Reactive dyes, as indeed all dyes, should be handled carefully to minimise worker exposure. The product label should therefore include a safety phrase that breathing of dust (for solid formulations) or spray (for liquid formulations) should be avoided.

 

In the European Union the appropriate S-phrases must be used, i.e.

 

S22  do not breathe dust

S23  do not breathe spray

 

In the Globally Harmonized System the Precautionary statements for Prevention and Response advice must be used:

 

                Precautionary statements:

                Prevention: Avoid breathing dust and spray

                Response:  If respiratory symptoms occur, seek medical advice

 

 

For listed Reactive dyes

 

There is evidence that certain Reactive dyes have caused respiratory sensitisation in workers occupationally exposed to them. These dyes are listed in the table. For these dyes, and any others which are concluded, on individual assessment, to cause respiratory sensitisation this hazard should be indicated on the safety data sheet and product label.

 

In the European Union the following symbols and phrases must be used.

 

For solid formulations:

Xn      (harmful)

R42    may cause sensitisation by inhalation

S22    do not breathe dust

 

 

For liquid formulations:

Xn      (harmful)

R42    may cause sensitisation by inhalation

S23    do not breathe spray

 

In the Globally Harmonized System these dyes have to be classified as Respiratory Sensitizers

 

Hazard Category         1

Signal word                  Danger

 

Symbol GHS08     

 

Hazard statements:

H334 - May cause allergy or asthma symptoms or breathing difficulties if inhaled

Precautionary statements:

P 261 - Avoid breathing dust / mist… (according Physical form of formulation)

P 285 – In case of inadequate ventilation wear respiratory protection

 

 

The substance Reactive Red 065, CAS 70210 -40 -1, EC 274 -437 -2 is listed in the "List of Reactive dyes to be classified as respiratory sensitizers" page 31 ff. within that document. Labelling as a respiratory sensitizer is recommended.

Interpretation of results:
sensitising
Conclusions:
Reactive Red 065, CAS 70210 -40 -1, EC 274 -437 -2 is recommended to be labelled as a respiratory sensitizer by ETAD based on international experience gained in handling this dye.
Executive summary:

Reactive Red 065, CAS 70210 -40 -1, EC 274 -437 -2 is recommended to be labelled as a respiratory sensitizer by ETAD based on international experience gained in handling this dye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Justification for classification or non-classification

Based on the findings in the skin sensitisation study the Reactive Red 65 should be classified as skin and respiratory sensitiser according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.