Registration Dossier

Administrative data

Description of key information

The test substance is not classified as 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:
31 October to 3 November 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 2.1 - 3.1 kg
- Housing: single
- Diet: Altromin 2123 maintenance diet ad libitum and approx. 15 g hay/day
- Water: deionized chlorinated water ad libitum
- Acclimation period: NA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 31. Oct To: 03 Nov. 1989
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
500 mg pased with 0.4 mL of 0.9% physiological saline solution
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 4 hours

About 24 hours prior dermal treatment the fur of three rabbits was removed from the dorsal part of the torso with an electric hair clipper over an area of approximately 25 cm2. Only animals with intact skin were used.

500 mg of Reaktiv-Rot F-66813 FW (pasted with 0.40 mL 0.9% NaCI-solution) was applied to each animal. The pasted test substance was spread over the whole surface of the 2.5 x 2.5 cm cellulose patch of a surgical plaster (specially produced by Beiersdorf AG, Hamburg). The plaster strip was then fixed to the prepared skin and covered with a semi-occlusive bandage.

The exposure period was 4 hours. After the end of the 4 hours exposure period remnants of the still remaining test substance were removed from the skin with lukewarm water.

The skin was examined 30 - 60 minutes and 24, 48 and 72 hours after removal of the plaster.

Erythema, eschar formation and edema were evaluated numerically. All other changes of the skin were recorded.


SCORING SYSTEM:
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond area of exp.) 4
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:
There were no signs of skin irritations during the whole study period. However, large areas of the treated skin were red discolored during the whole course of the study.
Other effects:
Reddish discoloration at treated skin during entire observation time
Interpretation of results:
GHS criteria not met
Conclusions:
Reaktiv-Rot F-66813 FW is not irritating to the skin and not subject to labelling requirements
Executive summary:

Based on the results of the present rabbit primary dermal irritation study Reaktiv-Rot F-66813 FW is not irritating to the skin and not subject to labelling requirements according to the classification critera of the Directive 83/467/EEC and the Ordinance on Hazardous Substances.

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:
7 November to 10. November 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 2.1 - 3.1 kg
- Housing: single
- Diet: Altromin 2123 maintenance diet ad libitum and approx. 15 g hay/day
- Water: deionized chlorinated water ad libitum
- Acclimation period: NA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 07 Nov. To: 10 Nov. 1989
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm physiological saline solution
- Time after start of exposure: 24 hours

SCORING SYSTEM:
1, 24, 48, and 72 hours, then at 1 week post treatment

About 24 hours before the start of the study the eyes of all animals to be treated were examined under UV light for possible corneal lesions after instillation of one drop of a 0.01 % fluorescine-sodium solution. Only animals without ocular abnormalities were used for the study.
Every 100 mg Reaktiv-Rot F-66 813 FW was administered once into the conjunctival sac of the left eye of three rabbits. In each case, the untreated eye served as a control. 24 hours after the administration of the test substance and also at the designated examination times at which the treated eyes still showed discharge, or a corneal examination with fluorescine-sodium solution was performed the treated eyes were washed thoroughly with isotonic saline (approx. 37° C).

The eyes were examined 1, 24, 48 and 72 hours after administration of the test substance. After 24 and 72 hours the cornea was additionally examined under UV-light for corneal lesions after instillation of one drop of a fluorescine-sodium solution (0.01 %). Lesions in cornea, iris and conjunctivae were graded numerically. All other changes were recorded.


1. Conjunctivae

Redness: lids and/or nictitating membranes
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis: lids and/or nictitating membranes
No swelling 0
Any amount different from normal (includes nictating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4


2. Iris
Normal 0
Markedly deepened rugae, congestion, swelling, slight
circumcorneal hyperaemia: or injection: iris still reacting to light
(a sluggish reaction is positive) 1
Haemorrhage, gross destruction, or no reaction to light. 2


3. Cornea

Opacity-degree of density (area most dense taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight
dulling of normal lustre): details of iris clearly visible 1
Easily discernible translucent area: details of iris slightly obscured 2
Nacrous area: no details of iris visible: size of pupil barely discernible 3
Opaque cornea: iris not discernible through the opacity 4

Affected area (opacity or stained by fluorescine test)
No translucense 0
Punctiform to one quarter 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4


TOOL USED TO ASSESS SCORE: fluorescein staining and UV-light 24 and 72 hours after treatment
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
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:
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
Irritant / corrosive response data:
One hour after administration the animals' conjunctivae showed a diffuse crimson color and swelling with about half closed lids. Reddish discolored discharge stained by the test substance occurred. All animals showed a pronounced hyperemia of several blood vessels of the conjunctiva 24 hours after administration.
All changes were fully reversible within 2 days.
Other effects:
The iris was sporadically red discolored during the whole course of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the present study, Reaktiv-Rot F-66 813 FW is not irritating to the eye. According to the classification criteria of Directive 83/467/EEC and the Ordinance on Hazardous Substances Reaktiv-Rot F-66 813 FW is not subject to labeling requirements.
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 according to EC-Guideline B.5. Acute Toxicity Eye Irritation of Directive 84/449/EEC: Commission Directive of April 25,1984 adapting for the sixth time Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of hazardous substances to the technical progressand meets the requirements ofOECD Guideline for Testing of Chemicals, 405 "Acute Eye Irritation / Corrosion", OECD 1981.Updated Guideline, adopted : 24th February 1987. Study conducted in compliance with GLP.

 

Based on the results of the present rabbit primary eye irritation studyReaktiv-Rot F-66813 FW is not irritating to the eye and not subject to labelling requirements.

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

Additional information

Skin irritation / Corrosion.

A single study was evaluated on this endpoint. In these the substance was tested for primary dermal irritation and corrosiveness. Due to staining of the skin, redness etc could not be evaluated; nevertheless, no other inflammatory signs (eschar or oedema formation) became apparent within the observation period of 7 days. 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. Effects were noted in all animals assessed; however these were fully reversible within 48 hours. No classification is applicable.

 

Respiratory irritation

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

 

The following information is taken into account for any hazard / risk assessment:

Skin and eye irritation are discussed.

Value used for CSA:

-         Skin irritation / corrosion: not irritating

-         Eye irritation: not irritating

Justification for classification or non-classification

The above studies have all 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 irritation effects is therefore required.