Registration Dossier

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation, other
Remarks:
animal study, not further specified
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:
skin sensitisation, other
Remarks:
animal study, not further specified
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
Version / remarks:
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.
Type of study:
not specified
Justification for non-LLNA method:
data derived from publically available website
Species:
other: not specified; "animal"
Strain:
not specified
Sex:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitizing
Conclusions:
Information was gathered from a peer-reviewed database, hence, the information can be considered as sufficiently reliable to assess the sensitizing potential of the test item. It evidently gave no evidence of sensitization in an animal study.
Executive summary:

CAS 147-14-8 evidently gave no evidence of sensitization in an animal study.

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
Version / remarks:
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.
Type of study:
not specified
Justification for non-LLNA method:
data derived from publically available website

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

In vivo test system

Test animals

Species:
other: not specified; "animal"
Strain:
not specified
Sex:
not specified

Results and discussion

In vitro / in chemico

Results
Remarks on result:
no indication of skin sensitisation

In vivo (non-LLNA)

Results
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
other: not sensitizing
Conclusions:
Information was gathered from a peer-reviewed database, hence, the information can be considered as sufficiently reliable to assess the sensitizing potential of the test item. It evidently gave no evidence of sensitization in an animal study.
Executive summary:

CAS 147-14-8 evidently gave no evidence of sensitization in an animal study.