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Description of key information

The test substance is not irritating to skin or eyes.

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:
From August 8, 1989 to August 11, 1989
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 (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst
- Age at study initiation: about 3-5 months
- Weight at study initiation: 2.9-3.4 Kg
- Housing: In fully air-conditioned rooms in separate cages arranged in a battery
- Diet: Altromin 2123 (Altromin GmbH, Lage/Lippe) ad libitum and hay (approx. 15g daily)
- Water: water from automatic water dispenser ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20±3°C
- Humidity: 50±20 %
- Lighting time: 12 hours daily
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
physiological saline
Remarks:
to form a paste
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g, with 0.55 ml of isotonic saline solution

VEHICLE
- Amount(s) applied: 0.55 mL of isotonic saline
Duration of treatment / exposure:
4 hours
Observation period:
examination after 30-60 minutes, 24, 48, and 72 hours.
Number of animals:
3
Details on study design:
TEST SITE
- Preparation: about 24h before the start of the study the hair in the dorsal region on the body was removed with an electric clipped over an area of 25 cm^2. Only animals with intact skin were used.
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: cellulose patch on a piece of surgical plaster (produced by Beiersdorf Aktiengesellschaft)

REMOVAL OF TEST SUBSTANCE
- washing: yes, with warm tap water
- Time after start of exposure: after 4 hours

SCORING SYSTEM: according to the score of Draize

Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of systemic toxicity were observed during the 72 hours of observation
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is detemined to be not irritating to the skin.
Executive summary:

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 test substance pasted with 0.55 ml isotonic saline. The substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (specially produced by Beiersdorf 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.

No signs of irritation occurred during the whole study.

The skin of the animals was discoloured orange 30 - 60 minutes after removal of the patches up to the end of the study.

Testing 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:
from August 15, 1988 to August 18, 1988
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 (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: about 3-5 months
- Weight at study initiation: 3.3-3.7 Kg
- Housing: In fully air-conditioned rooms in separate cages arranged in a battery
- Diet: Altromin 2123 (Altromin GmbH, Lage/Lippe) ad libitum and hay (approx. 15 g daily)
- Water: water from automatic water dispenser ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20±3°C
- Humidity: 50±20 %
- Photoperiod: 12 hours cycle dark/light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 100 mg
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
The eyes were examined 1, 24, 48, 72 hours after application of the test substance.
Number of animals or in vitro replicates:
3
Details on study design:
PREPARATION
About 24 hours before the start of the study the test eyes of all animal were examined under UV light for corneal lesion after instillation of one drop of a 0.01% fluorescein-sodium solution. Only animal without ocular abnormalities were used for the study.

REMOVAL OF TEST SUBSTANCE
- Washing: yes with isotonic saline at 37°C
- Time after start of exposure: 24 hours

TOOL USED TO ASSESS SCORE: fluorescein; at 24 and 72 hours the eyes were also examined for corneal lesion under UV light after instillation of one drop of 0.01% fluorescein-sodium solution.

SCORING SYSTEM: according to OECD guideline 405
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One hour up to 2 days after application the conjunctivae of the animals showed an evident hyperemia of the blood vessels to a diffuse, deeper crimson reddening and a slight to obvious swelling. Additionally a clear, red-orange colored discharge was observed in two animals one hour after application. 3 days after application the signs of irritation were reversible. One hour up to 2 days after application the conjunctivae of the animal showed an evident hyperemia of the blood vessels to a diffuse, deeper crimson reddening and a slight to obvious swelling. Additionally a clear, red-orange colored discharge was observed in two animals one hour after application. 3 days after application the signs of irritation were reversible.
Interpretation of results:
GHS criteria not met
Conclusions:
Testing for primary eye irritation in the rabbit showed, that the substance is not irritating to eyes.
Executive summary:

The test substance was examined for eye irritating effects in rabbit eyes according to OECD testing guideline 405.

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 % f1uorescein-sodium solution. Only animals without ocular abnormalities were used for

the study.

100 mg test substance was applied 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 application 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 application of the test substance.

At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution. Lesions in cornea. iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded.

One hour up to 2 days after application the conjunctivae of the animals showed an evident hyperaemie of the blood vessels to a diffuse, deeper crimson reddening and a slight to obvious swelling. Additionally a clear, red-orange coloured discharge was

observed in two animals one hour after application. Three days after application the signs of irritation were reversible.

Based on the individual scores after 24, 48 and 72 hours, the following mean values were calculated:

Opacity of cornea all animals 0.0; iris all animals 0.0; redness of conjunctiva all animals 0.4; chemosis of conjunctiva all animals 0.0

Hence, the substance is not irritating to the eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For skin irritation testing, each animal was treated with 0.5 g Reactive Orange 72/78 pasted with 0.55 ml isotonic saline. 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.

No signs of irritation occurred during the entire study.

The skin of the animals was discoloured orange 30 - 60 minutes after removal of the patches up to the end of the study.

Testing of Reactive Orange 72/78 for primary dermal irritation in the rabbit showed that the substance is not irritating to skin.

100 mg Reactive Orange 72/78 was applied once to the conjunctival sac of the left eye of three rabbits. The untreated eyes served in each case as a control. The eyes were examined 1, 24, 48 and 72 hours after application of the test substance.

At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01% fluorescein-sodium solution. Lesions in cornea. iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded.

One hour up to 2 days after application the conjunctivae of the animals showed an evident hyperaemie of the blood vessels to a diffuse, deeper crimson reddening and a slight to obvious swelling. Additionally a clear, red-orange coloured discharge was observed in two animals one hour after application. 3 days after application the signs of irritation were reversed.

Based on the individual scores after 24, 48 and 72 hours, the following mean values were calculated:

Opacity of cornea all animals 0.0; iris all animals 0.0; redness of conjunctiva all animals 0.4; chemosis of conjunctiva all animals 0.0

Testing of Reactive Orange 72/78 for primary eye irritation in the rabbit showed, that the substance is not irritating to the eye.

Justification for classification or non-classification