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Administrative data

Description of key information

The substance is not irritant to skin or eye

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 November 1998 to 27 November 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Species: New Zealand albino rabbit
Origin: Charles River Deutschland GmbH 88353
Number of animals: 3
Body weight at start of the study: 3.2 - 3.5 kg
Animal maintenance: in fully air-conditioned rooms in separate cages arranged in a battery
Room temperature: 20±3°C
Relative humidity: 50±20%
Lighting time: 12 hours daily
Acclimatization: 1 week under study conditions
Food: ssniff®1 K-H (V2333), ad libitum and hay (approx. 15 g daily)
Water: water from automatic water dispensers, ad libitum
Animal identification: numbered ear tags
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
deionised
Controls:
yes, concurrent no treatment
Amount / concentration applied:
500 mg per patch
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
About 24 hours before the start of the study the hair in the dorsal region of the body of 3 rabbits was removed with an electric clipper over an area of about 25 cm2. Only animals with intact skin were used.

Each animal was treated with 0.5 g Reaktiv-Orange DYPR 1410 pasted with 0.3 ml deionized water. The substance was administered over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (specialty produced by Beiersdorl Aktiengesellschaft). The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

The exposure period was 4 hours. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water.
Examinations of the skin took place after 30 - 60 minutes as well as 24, 48 and 72 hours after removal of the patches.

Erythema, eschar formation and oedema were evaluated numerically according to the score of DRAIZE . All other changes of the skin were recorded.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean value
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean value
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean value
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean value
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean value
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean value
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
30 - 60 minutes up to 48 hours after decontamination the animals showed very slight erythema up to well-defined erythema and sporadically very slight oedema.
72 hours after decontamination all signs of irritation were reversed.
Other effects:
During the whole observation period the skin of the animals were discoloured orange.

Generalised Results by Animal –Animals Against Parameters – Multiple Times

Activity – Skin Irritation Results

Study: 98.0701 – Reaktiv-Orange DYPR 1410 – Skin Irritation Test in Rabbits

Group Sex

Animal Number

Day Number

Time Slot

Bodyweight g

Treated Flank

Duration Treatment

Erythema

Edema

1f

70

1

Treatment

3450

Left

4 hours

 

 

 

30-60 min. After decontamination

 

 

 

1

0

2

24 hours after decontamination

 

 

 

1

0

3

48 hours after decontamination

 

 

 

0

0

4

72 hours after decontamination

 

 

 

0

0

71

1

Treatment

32060

Left

4 hours

 

 

 

30-60 min. After decontamination

 

 

 

1

0

2

24 hours after decontamination

 

 

 

2

1

3

48 hours after decontamination

 

 

 

1

0

4

72 hours after decontamination

 

 

 

0

0

72

1

Treatment

3290

Left

4 hours

 

 

 

30-60 min. After decontamination

 

 

 

1

0

2

24 hours after decontamination

 

 

 

1

0

3

48 hours after decontamination

 

 

 

0

0

4

72 hours after decontamination

 

 

 

0

0

 

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study Reaktiv-Orange DYPR 1410 is not irritating to skin.
Executive summary:

Testing for primary dermal irritation provides information on the irritant effect of the test substance on the skin following a single dermal administration and serves as a basis for classification and labelling. The present study was conducted in compliance with EEC-Guideline B.4."Acute Toxicity Skin Irritation" of the Directive 92/69/EEC and OECD Guidelines for Testing of Chemicals, 404 "Acute Dermal Irritation / Corrosion”. This study was conducted in compliance with the Principles of Good Laboratory Practice (GLP).


Testing of Reaktiv-Orange DYPR 1410 for primary dermal irritation in the rabbit showed, that the substance is not irritating to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 December 1998 to 11 December 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species: New Zealand albino rabbit
Origin: Charles River Deutschland GmbH 88353 KiSlegg
Number of animals: 3
Body weight at start of the study: 3.5-3.8 kg
Animal maintenance: in fully air-conditioned rooms in separate cages arranged in a battery
Room temperature: 20 ± 3°C
Relative humidity: 50 ± 20 %
Lighting time: 12 hours daily
Acclimatization: 1 week under study conditions
Food: ssniff® K-H (V2333), ad libitum and hay (approx. 15 g daily)
Water: water from automatic water dispensers, ad libitum
Animal identification: numbered ear tags
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg per eye
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
About 24 hours before the start of the study the test eyes of all animals were examined under UV light for corneal lesions after instillation of one drop of a 0.01 % fluorescein-sodium solution. Only animals without ocular abnormalities were used for the study.

100 mg Reaktiv-Orange DYPR 1410 was administered once to the conjunctival sac of the left eye of three rabbits. The untreated eyes served in each case as a control.

24 hours after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution took place, the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C.

The eyes were examined 1, 24, 48 and 72 hours after administration of the test sub¬stance. At 24 and 72 hours, the eyes were also examined for corneal lesions under UV light after instillation of one drop of a 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
72 hours after administration all signs of possible irritation were reversed.
Other effects:
One hour up to 48 hours after administration the conjunctivae of the animals showed definitely injected blood vessels up to a diffuse crimson red colour and very slight swellings. Additionally, reddish or substance coloured eye discharge was noted in two animals one hour after administration.

Generalised Results By Animal – Animals Against Parameters – Multiple Times

Activity: - Eye Irritation Results

Study: 98.0702 – Reaktiv-Orange DYPR 1410 – Eye Irritation Test in Rabbits

Group Sex

Animal No.

Day No

Time Slot

Opacity Grade

Opacity Area

Iris

Redness

Chemosis

Discharge

1f

71

1

1 hour after treatment

0

0

0

1

1

0

2

24 hours after treatment

0

0

0

2

1

0

3

48 hours after treatment

0

0

0

1

0

0

4

72 hours after treatment

0

0

0

0

0

0

72

1

1 hour after treatment

0

0

0

1

1

1

2

24 hours after treatment

0

0

0

1

1

0

3

48 hours after treatment

0

0

0

0

0

0

4

72 hours after treatment

0

0

0

0

0

0

79

1

1 hour after treatment

0

0

0

1

1

1

2

24 hours after treatment

0

0

0

0

0

0

3

48 hours after treatment

0

0

0

0

0

0

4

72 hours after treatment

0

0

0

0

0

0

Nominal Dose: Group 1 – 100mg undiluted

Interpretation of results:
GHS criteria not met
Conclusions:
Testing of Reaktiv-Orange DYPR 1410 for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.
Executive summary:

Testing for primary irritation in the rabbit eye provides information on ocular lesions after a single administration of the test substance to the conjunctival sac of the eye and serves as a basis for classification and labelling. The present study was conducted in compliance with EEC-Guideline B.5."Acute Toxicity Eye Irritation" of the Directive 92/69/EEC and OECD Guidelines for Testing of Chemicals, 405 "Acute Eye Irritation / Corrosion". This study was conducted in compliance with GLP.


One hour up to 48 hours after administration the conjunctivae of the animals showed definitely injected blood vessels up to a diffuse crimson red colour and very slight swellings. Additionally, reddish or substance coloured eye discharge was noted in two animals one hour after administration. 72 hours after administration all signs of irritating were reversible.


Testing of Reaktiv-Orange DYPR1410 for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.


 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / Corrosion.

A single study was evaluated on this endpoint.  30 - 60 minutes up to 48 hours after decontamination the animals showed very slight erythema up to well-defined erythema and sporadically very slight oedema.  72 hours after decontamination all signs of irritating were reversible. Signs of toxicity were not observed. This evidence indicates no hazard potential to the skin and the test substance may therefore be regarded as 'not irritating to the skin’. It is not a dermal corrosive. No risk phrase or classification is required.

 

Eye irritation.

 A single study was evaluated on this endpoint. In these the substance was tested for acute irritation and was found not to be an irritant to the rabbit eye. One hour up to 48 hours after administration the conjunctivae of the animals showed definitely injected blood vessels up to a diffuse crimson red colour and very slight swellings. Additionally, reddish or substance coloured eye discharge was noted in two animals one hour after administration. 72 hours after administration all signs of irritating were reversible. No classification is applicable.

 

Respiratory irritation

Respiratory irritation was not assessed; however no effects on the animals were noted in any associated studies.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimisch 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 irritation effects is therefore required.