Registration Dossier

Administrative data

Description of key information

Based on studies in guinea pigs, the substance is not considered to be a skin sensitiser.

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:
13. November to 15 December. 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
84/449/EWG, B.6 (Magnusson-Kligman-Test)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was already available
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Weight at study initiation: 264 to 364 g
- Housing: 5/cage
- Diet: Altromin 3112 guinea pig maintenance diet ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From: 13-Nov To: 15-Dec-1989
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
5 % / 4 x 0.1 mL
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Concentration / amount:
5 % / 0.5 mL
Day(s)/duration:
Day 8 for 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
5 % / 0.5 mL
Day(s)/duration:
Day 22 for 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Determination of primary non-irritating concentration: 6
Determination of the intradermal tolerance: 3
Number of animals in attending group: 5
Number of animals in test group: 10 Number of animals in negative control group: 5
Details on study design:
RANGE FINDING TESTS:
- Determination of primary non-irritating concentration: dermal-occlusive exposure for 24 hours - 3 concentrations (25%, 5%, 1%)
- Determination of the intradermal tolerance: intradermal injection: 2 x 3 concentrations (5%, 1%, 0.2%)

MAIN STUDY
A. INTRADERMAL INDUCTION
- No of Injections: 2 x 3 preparations: 50% FCA, TS in 0.9% NaCl, 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 8
- Site: shoulder

B. DERMAL INDUCTION EXPOSURE
- No. of exposures: one
- Exposure period: 48 hours
- Test groups: TS in 0.9% NaCl
- Control group: 0.9% NaCl
- Site: shoulder
- Frequency of applications: single
- Duration: Day 8 to Day 22
- Concentrations: 5%

C. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22 (15 for attending group)
- Exposure period: 24 hours
- Test groups: TS + water
- Control group: TS + 0.9% NaCl
- Site: right flank: TS; left flank: 0.9% NaCl
- Concentrations: 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 5% TS would not lead to dermal irritation in animals pre-treated with 50% FCA.
Positive control substance(s):
yes
Remarks:
bi-annual validation of assay
Positive control results:
valid
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
skin slightly reddish stained by TS not affecting evaluation
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
skin slightly reddish stained by TS not affecting evaluation
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
skin slightly reddish stained by TS not affecting evaluation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
skin slightly reddish stained by TS not affecting evaluation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
test system was checked twice a year but details were not included in this report

Signs of irritation during induction:
Administration of test substance in physiological saline solution led to reddening and edema at the adminstration site. All test substance treated sites were reddish stained by the test compound.


Evidence of sensitisation of each challenge concentration: none

Interpretation of results:
GHS criteria not met
Conclusions:
There was no evidence of a positive reaction in animals after challenge treatment with Reaktiv-Rot F-66813 FW in the present study.
According to the classification criteria of Directive 83/467/EEC, Reaktiv-Rot F-66813 FW is not sensitizing in the guinea pig maximization test and therefore not subject to labelling requirements.
Executive summary:

The skin sensitizing potential of Reaktiv-Rot F-66813 FW was examined in Pirbright-White guinea pigs with the maximization test.

Intradermal and dermal induction as well as the dermal challenge treatment were performed using 5% Reaktiv-Rot F-66813 FW in 0.9% NaCl.solution.

Based on the results of the present study, Reaktiv-Rot F-66813 FW is not sensitizing and not subject to labelling requirement.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Sensitisation was assessed using the Magnusson and Kligman sensitisation assay. During the induction phase of the study, no irritation reactions were noted in both control and test groups. All sites treated with the test substance were stained; therefore redness etc could not be properly evaluated. 

 

On the basis of the results, the substance cannot be considered to be a skin sensitiser.

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 or the proper de-dusting of the substance (spay dried in closed system from aqueous solution directly after synthesis) 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 above study has been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the studies were conducted to GLP an 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 effects is therefore required.