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Toxicological information

Eye irritation

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Physical state: Not stated, but it is common knowledge that this test substance is a solid

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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)



Applicant's summary and conclusion

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."