Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (equivalent or similar to OECD 404)

Eye irritation: not irritating (equivalent or similar to OECD 405)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Minor deviations without an effect on the results: - According to the guideline, the relative humidity in the animal room should be 30 - 70 %. In this study the humidity was slightly higher (55% +/- 25 %). - According to the guideline, approx. 24 h before the test the fur should be removed by clipping or shaving. In this study it was not stated when the fur was removed. - According to the guideline, justification for choice of vehicle must be stated. In the report it was not stated, if the test substance (solid) was moistened with water or a vehicle. - According to the guideline, the age, the weight at the conclusion of the test and the source of the animals should be stated. This information was missing in the report. - According to the guideline a narrative description of the degree and nature of irritation observed must be included in the report. This was missing in this report. Only the scoring of erythema and oedema were stated.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992-07-17
Deviations:
yes
Remarks:
, see "rational for reliability"
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Authorised supplier
- Weight at study initiation: animal #1: 2652 g; animal #2: 2501 g; animal #3: 2654 g
- Housing: Individual stainless steel cages, brand Tecniplast
- Diet: Daily dose of 150 g of special diet for experimental rabbits, provided by an authorised provider
- Drink (ad libitum): Automatic, treated and filtered at 5 µm
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ° C (+/- 2°C)
- Relative humidity: 55 % (+/- 25 %)
- Air: Renewed 15 times per hour and prefiltered at 5 µm
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: No data: "In case of solid samples, 0.5 g are applied humidifying sufficiently with water (or appropriate fluid) to ensure a good contact with skin."
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g are applied humidifying sufficiently with water (or appropriate fluid) to ensure a good contact with skin.

Duration of treatment / exposure:
maximum time of exposure was 4 hours
Observation period:
1 hour, 24 hours, 48 hours, 72 hours, 7 days and 14 days after removal of the bandages
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: The rabbits were shaved at the back retro-scapular area close to the vertebral column, in a 20 cm long, 13 cm wide rectangle. Once the rabbit has been shaved, the sample was applied directly on the skin, on a surface approx. 6 cm^2.
- Type of wrap if used: The test site was covered with a bandage, it was held with plaster and covered with a hypoallergenic plaster bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The studied sample was softly removed with water or appropriate solvent.
- Time after start of exposure:Once the period of exposure was over.

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
All skin effects observed were reversed by day 14.
1-hour observation in rabbits:
Animal #1:
Erythema: Score 1 (very slight (hardly perceptible)
Oededma: Score 0 (none)
Animal #2:
Erythema: Score 1 (very slight (hardly perceptible)
Oededma: Score 0 (none)
Animal #3:
Erythema: Score 1 (very slight (hardly perceptible)
Oededma: Score 0 (none)
Interpretation of results:
GHS criteria not met
Conclusions:
Given that a mean value of 2 or higher was not observed in any of the tested animals, it can be concluded that the sample submitted "VERDE-D7 (B2240) ((Hematite chromium green black) does not generate skin irritation.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as skin irritant.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Minor deviations from the guideline without effect on the results of the study: - According to the guideline, adult albino rabbits should be used for the test. The age of the animals was missing in the report. - According to the guideline, the humidity in the animal room should be 30 -70 %. In this study the humidity was slightly higher (55 % +/- 25%). - According to the guideline, after the substance has been placed in the conjunctival sac the eyelids are gently held together for about one second. This statement was missing in the report.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987-02-24
Deviations:
yes
Remarks:
, see "rational for reliability"
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Authorised supplier
- Weight at study initiation: animal #1: 2067 g; animal #2: 2430 g; animal #3: 2025 g
- Housing: Individual stainless steel cages, brand Tecniplast
- Diet: Daily dose of 150 g of special diet for experimental rabbits, provided by an authorised provider
- Drink (ad libitum): Automatic, treated and filtered at 5 µm
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C (+/- 2°C)
- Relative humidity: 55 % (+/- 25 %)
- Air: Renewed 15 times per hour and prefiltered at 5 µm
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g is administered, separating the lower eyelid in the conjunctival bag of one of the eyes. The other one will be used as reference.
Observation period (in vivo):
1 hour, 24 hours, 48 hours, 72 hours and 7 days after administration
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
Not stated

SCORING SYSTEM: Draize Scoring system

TOOL USED TO ASSESS SCORE: In order to faciliatate the evaluation of the reactions, light from a manual lamp will be used and after 24 hours of administration, fluorescein will also be used to check injuries in the cornea.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: At the 1 and 24 hour readings, opacity of the cornea of level 1 was observed, affecting 1/4 of the eyeball, which disappeard within 48 hours.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: At the 1 and 24 hour readings, opacity of the cornea of level 1 was observed, affecting 1/4 of the eyeball, which disappeared within 48 hours.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: At the 1 and 24 hour readings, opacity of the cornea of level 1 was observed, affecting 1/4 of the eyeball, which disappeared within 48 hours.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
All ocular effects observed reversed by day 7.
1 hour observation of the rabbits:
Rabbit #1:
- Cornea: Score 1 ( Dispersed or diffuse opacity areas (different from a slight decrease from normal brightness), details of iris clearly visible)
- Iris: Score 1 (Folding clearly deeper, congestion, swelling, moderate pericornea hyperemia, or injected conjunctivia, either of these symptoms or any of their combination, iris still reacts to light (slow reaction is a positive)
- Erythema of conjunctiva: Score 2 (Diffuse crimson colouration, individual blood vessels easily distinguishable)
- Oedema of the conjunctiva: Score 2 (Obvious tumefaction with partial destruction of eyelids)
Rabbit #2:
- Cornea: Score 1 ( Dispersed or diffuse opacity areas (different from a slight decrease from normal brightness), details of iris clearly visible)
- Iris: Score 1 (Folding clearly deeper, congestion, swelling, moderate pericornea hyperemia, or injected conjunctivia, either of these symptoms or any of their combination, iris still reacts to light (slow reaction is a positive)
- Erythema of conjunctiva: Score 2 (Diffuse crimson colouration, individual blood vessels easily distinguishable)
- Oedema of the conjunctiva: Score 2 (Obvious tumefaction with partial destruction of eyelids)
Rabbit #3:
- Cornea: Score 1 ( Dispersed or diffuse opacity areas (different from a slight decrease from normal brightness), details of iris clearly visible)
- Iris: Score 1 (Folding clearly deeper, congestion, swelling, moderate pericornea hyperemia, or injected conjunctivia, either of these symptoms or any of their combination, iris still reacts to light (slow reaction is a positive)
- Erythema of conjunctiva: Score 2 (Diffuse crimson colouration, individual blood vessels easily distinguishable)
- Oedema of the conjunctiva: Score 2 (Obvious tumefaction with partial destruction of eyelids)



Interpretation of results:
GHS criteria not met
Conclusions:
Given the extent of the observed eye effects, the substance "Verde D7" (B2240) (Hematite chromium green black) is not considered to require classification for eye irritation, for the following reasons:
- according to the criteria previously specified by Directive 67/548/EEC and subsequent regulations, this substance clearly does not require classification as an eye irritant.
- however, according to EC Regulation No. 1272/2008 and subsequent regulations, the test item would qualify as a borderline case for classification as eye irritant merely resulting from slight change in the interpretation criteria between the current Directive 67/548/EEC (basis for REACH) and the future EC Regulation No. 1272/2008.
- the criteria for assessment of the observed conjunctival redness is only mildly exceeded, whereas all other effects observed are far from any level that would require classification and are fully reversible within 7 days.
- finally, long-term industrial experience in practical handling and use shows an absence of human eye irritation incidents.

In conclusion, by applying a weight-of-evidence approach, a classification of the pigment hematite chromium green black according to EC Regulation No. 1272/2008 is considered to be obsolete. This proposal is also supported by the following statement in EC Regulation No. 1272/2008, Annex I, 3.3.2.7.2:"for those substances where there is pronounced variability among animal responses, this information shall be taken into account in determining the classification."


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

Respiratory irritation

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

Additional information

One study on skin irritation according to OECD TG 404 has been performed.that indicated a mean erythema score of 1.0, 1.0, 1.0 at time point 1, 24, 48h respectively after exposure, hence "Verde D7" (B2240) (Hematite chromium green black) does not generate skin irritation. All skin effects observed were reversed by day 14..

One study on eye irritation according to OECD TG 405 has been performed. All ocular effects observed reversed by day 7.Given the extent of the observed injuries the sample submitted "Verde D7" (B2240) (Hematite chromium green black) does not irritate the eyes.

Justification for classification or non-classification

Skin irritation in vivo:

erythema, mean animal #1, 24 -72h after application: score=1

edema, mean animal #1, 24 -72h after application: score=0

erythema, mean animal #2, 24 -72h after application: score=1       

edema, mean animal #2, 24 -72h after application: score=0

erythema, mean animal #3, 24 -72h after application: score=1       

edema, mean animal #3, 24 -72h after application: score=0

Given that a mean value of 2 or higher was not observed in any of the tested animals, it can be concluded that the sample submitted "VERDE-D7 (B2240) ((Hematite chromium green black) does not generate skin irritation. All skin effects observed were reversed by day 14.

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as skin irritant. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as skin irritant.

Eye irritation in vivo:

conjunctivae score, mean animal #1, 24 -72h: score=1.67   (fully reversible within 7d)

conjunctivae score, mean animal #2, 24 -72h: score=2        (fully reversible within 7d)

conjunctivae score, mean animal #3, 24 -72h: score=2        (fully reversible within 7d)

cornea score, mean animal #1, 24 -72h: score=0.33              (fully reversible within 48h)

cornea score, mean animal #2, 24 -72h: score=0.33              (fully reversible within 48h)

cornea score, mean animal #3, 24 -72h: score=0.33              (fully reversible within 48h)

iris score, mean animal #1, 24 -72h: score=0

iris score, mean animal #2, 24 -72h: score=0.33                     (fully reversible within 48h)

iris score, mean animal #3, 24 -72h: score=0.33                     (fully reversible within 48h)

chemosis score, mean animal #1, 24 -72h; score=0.67            (fully reversible within 72h)

chemosis score, mean animal #2, 24 -72h; score=0.67            (fully reversible within 72h)

chemosis score, mean animal #3, 24 -72h; score=0.67            (fully reversible within 72h)

Given the extent of the observed eye effects, the substance "Verde D7" (B2240) (Hematite chromium green black) is not considered to require classification for eye irritation, for the following reasons:

- according to the criteria previously specified by Directive 67/548/EEC and subsequent regulations, this substance clearly does not require classification as an eye irritant.

- however, according to EC Regulation No. 1272/2008 and subsequent regulations, the test item would qualify as a borderline case for classification as eye irritant merely resulting from slight change in the interpretation criteria between the current Directive 67/548/EEC (basis for REACH) and the future EC Regulation No. 1272/2008.

- the criteria for assessment of the observed conjunctival redness is only mildly exceeded, whereas all other effects observed are far from any level that would require classification and are fully reversible within 7 days.

- finally, long-term industrial experience in practical handling and use shows an absence of human eye irritation incidents.

 

In conclusion, by applying a weight-of-evidence approach, a classification of the pigment hematite chromium green black according to EC Regulation No. 1272/2008 is considered to be obsolete. This proposal is also supported by the following statement in EC Regulation No. 1272/2008, Annex I, 3.3.2.7.2:"for those substances where there is pronounced variability among animal responses, this information shall be taken into account in determining the classification."

Respiratory irritation

The classification as respiratory irritant is covered under the endpoint specific target organ toxicity- single exposure. Please refer to the endpoint summaries on acute toxicity (endpoint 7.2) for further information.