Registration Dossier

Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
peer-reviewed database
Cross-reference
Reason / purpose for cross-reference:
read-across source
Remarks:
link to target
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
peer-reviewed database, read-across
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The ideal structure of the registered substance is a complex which consists of iron2+ as central ions and a hemiprophyrazine ring as ligand. Therefore, the endpoint in question may be both covered with data on Fe2+ salts as well as hemiprophyrazines and structurally related substances. So the read-across can be performed on both common functional groups and common breakdown products, as the read-across substances are considered breakdown products of the target substance.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source Chemicals, for individual read-across from an analogue in the required endpoints:
- Iron dichloride, CAS 7758-94-3
- Copper, (29H,31H-phthalocyaninato(2-)-kappaN29,kappaN30,kappaN31,kappaN32)-, ((3-(dimethylamino)propyl)amino)sulfonyl derivs., CAS 68411-04-1
- Copper phthalocyanine, CAS 147-14-8
Target Chemical:
(8,20-Dihydro-8,20-diphenyl-5,24:12,17-diimino-7,10:22,19-dinitrilodibenz(f,p)(1,2,4,9,11,12,14,19)
octaazacycloicosinato(2-)-N25,N26,N27,N28)iron, CAS 50293-39-5
All substances do not contain impurities to an extent which is expected to alter the outcome of the experimental results or read-across approach.

3. ANALOGUE APPROACH JUSTIFICATION
There are no data on the respective endpoints for all read-across substances available, but if data is available on all endpoints, a clear trend is available. So in general, read-across is justified. In detail, for the single possible structural analogues, the following is concluded:
CAS 7758-94-3: Both substances contain a Fe2+ ion, and with respect to acute oral toxicity, the substance provides the worst case scenario. So an underestimation of the actual risk here is unlikely. With regard to skin sensitization, iron does not need to be regarded, as it is an endogenous substance and no cases of sensitization were ever reported. Regarding gene mutation in bacteria, it was consistently with all the other possible analogues negative, so read-across is justified. For the irritation endpoints, it is not suitable, as based on the counterion, there are acidic iron salts available, clearly overestimating the possible hazard.
CAS 68411-04-1 / CAS 147-14-8: both source and target chemical contain structurally highly related chelating rings, i.e. a hemiprophyrazine ring or a phthalocyanine ring, they predominantly only differ in the central ion. The organic ring bearing all the chelating nitrogen atoms are identical, the only differ in the way the benzyl rings are attached, which are nevertheless identical chemical groups. With regard to acute oral toxicity, their acute oral LD50 values are way above the limit of classification, the precautionary classification of the target chemical as Acute tox. Cat. 4 does certainly not underestimate the actual risk. Regarding gene mutation in bacteria, all possible analogues are consistently negative ±S9. With regard to irritation and sensitisation, the organic functional groups are more relevant than the central ions, so read-across is also here justified.

4. DATA MATRIX
There is currently no data on the target chemical available, so an estimation using a worst case approach based on the properties of the available surrogates will be used:
Property CAS 50293-39-5 (target) CAS 7758-94-3 (source 1) CAS 68411-04-1 (source 2) CAS 147-14-8 (source 3)
LD50 (oral) Acute tox. Cat. 4 >300, <2000 mg/kg (rats) > 5000 mg/kg (rats) > 10000 mg/kg (rats)
>16000 mg/kg (rabbits)
Skin irritation Not irritating No data No data Not irritating
Eye irritation Not irritating No data No data Not irritating
Skin sensitization Not sensitizing No data No data Not sensitizing
Gene mutation in bacteria Negative ± S9 Negative ± S9 (OECD 471) Negative ± S9 (OECD 471) Negative ± S9 (various assays)
Reason / purpose for cross-reference:
read-across source
Guideline:
other: no data
GLP compliance:
not specified
Remarks:
Despite that the database is up to date (2018), data may be gained prior to 2008, when no testing under GLP was required. This information is not available.
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
not specified
Duration of treatment / exposure:
not specified
Observation period (in vivo):
not specified
Duration of post- treatment incubation (in vitro):
not specified
Number of animals or in vitro replicates:
not specified
Irritation parameter:
other: irritation
Remarks on result:
no indication of irritation
Remarks:
Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not available
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not given
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not given
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not given
Irritant / corrosive response data:
Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.
Interpretation of results:
other: not irritating
Conclusions:
Information was gathered from a peer-reviewed database, hence, the information can be considered as sufficiently reliable to assess the irritating potential of the test item. Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.
Executive summary:

Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.

Data source

Reference
Reference Type:
other: peer-reviewed database
Title:
HSDB, Pigment Blue 15
Author:
HSDB
Year:
2018
Bibliographic source:
HSDB, https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+2925
Report date:
2018

Materials and methods

Test guideline
Guideline:
other: no data
GLP compliance:
not specified
Remarks:
Despite that the database is up to date (2018), data may be gained prior to 2008, when no testing under GLP was required. This information is not available.

Test material

Constituent 1
Reference substance name:
29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32 copper
EC Number:
205-685-1
EC Name:
29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32 copper
Cas Number:
147-14-8
IUPAC Name:
[29H,31H-phthalocyaninato(2-)-kappa~2~N~29~,N~31~]copper

Test animals / tissue source

Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data

Test system

Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
not specified
Duration of treatment / exposure:
not specified
Observation period (in vivo):
not specified
Duration of post- treatment incubation (in vitro):
not specified
Number of animals or in vitro replicates:
not specified

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: irritation
Remarks on result:
no indication of irritation
Remarks:
Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not available
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not given
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not given
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: information not given
Irritant / corrosive response data:
Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Conclusions:
Information was gathered from a peer-reviewed database, hence, the information can be considered as sufficiently reliable to assess the irritating potential of the test item. Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.
Executive summary:

Phthalocyanine blue was apparently non-irritating to the skin and eye of rabbits.