[2-(29H,31H-phthalocyaninylmethyl)-1H-isoindole-1,3(2H)-dionato(2-)-N29,N30,N31,N32]copper

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The variant with the higher substitution grade was tested for skin irritation in rabbits in a more stringent exposure regime compared to OECD testing guideline 404: Skin irritation was tested prior to the introduction of GLP and OECD testing guidelines (BASF 1976). The study is reported in sufficient detail for evaluation.

Twenty-four hours prior to dermal application, the backs of the rabbits were shaved over an area consisting of at least 10% of the total body surface. Two sites lateral to the midline of the back were used on each rabbit. Immediately before the application of the compound, the right hand side was abraded with the point of a sterile hypodermic needle. The abrasions were sufficiently deep to penetrate the stratum corneum but not to damage the dermis. The left hand side remained intact. 1g of the compound was applied in 50% aqueous suspension to both the abraded and intact test site on a 2.5cm square gauze pad. These were covered with aluminium foil secured with "Sleek" adhesive tape. After 24 hours the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made on days 1,2,5,7 and 8.

 

The test item caused blue staining of the test item on day 1. After that no local effects were seen. The 24h-occlusive exposure is more stringent than the 4h-semiocclusive treatment prescrirbed in OECD testing guideline 404. The substance does not react with air and is not volatile, so that the occlusive conditions have no influence on the outcome. The hihger substituted substance is therefore considered to be non irritating to skin.

The same protocol was used for testing the non-substituted copper phthalocyanine. A GLP compliant study following OECD guideline 404 is available for the quinacridone analoge. In all tests, the substances did not cause local any effects on the skin other than leaving a transient blue residue. The findings on the read-across substances are clearly below thresholds for classification and labelling. Therefore, the slight reduction in substitution grade (2.48 versus 1.4) has no influence on the hazard classification for the endpoint of skin irritation. The target substance is assessed as being not irritating to skin.

A general read-across justification with data matrices are copied into the CSR.

The target substance has been tested for eye irritation in a GLP-compliant BCOP assay (OECD 437) (BASF 2014). The test item was applied onto isolated bovine corneas. Bovine eyes are obtained as a by-product of freshly slaughtered cattle. As positive control, 750 μL of 20% (w/v) solution of Imidazole in de-ionized water was used. As a result, for the test substance, an IVIS of 29 was obtained. This value is below the threshold of 55 and indicates that there is no risk of serious damage to the eyes. Histological evaluation of the cornea revealed changes indicating minimal eye damage.

As the BCOP assay only addresses serious eye damage and not “simple” eye damage, experimental data for the analogue substance with an average higher substitution grade is used for furthe assessment.

For eye irritation, the variant with the higher substitution grade was tested in rabbits prior to the introduction of GLP and OECD testing guidelines (BASF 1976). The study is reported in sufficient detail for evaluation.

The procedure is similar to OECD testing guideline 405. It differs in the shorter observation time of 8 days and in that only 2 animals (Vienna White rabbits) were used.

Ca 50 mg of the test item was applied into one eye of each rabbit without the use of a vehicle. Considering the relative density of 2.01, this is likely to amount to a volume of 0.1ml as required by the OECD testing guidline. The untreated eye served as control.

The test substance was not washed out. A scoring system translatable to Draize Scores was applied. On day eight, the eyes were investigated using fluorescein.

After 1h of application, grade 2 (of max 4) of irritation and dark bluish substance residues were observed for the treated eye of one animal. Grade 2 irritation (cornea and conjunctivae) was also observed at the 24h reading in one animal. Cornea findings were no longer observed at 24 and conjunctivae findings no longer at the 48h reading and no further effects were observed until the last investigation on day 8. No chemosis was observed at any time point. The second animal only showed signs of irritation at the 1h time point. These findings are clearly below the criteria for classification and labelling according to GHS criteria. The lower average substitution grade of the target substance neither introduces reactive groups nor does it introduce unkonwn components. The minimum size and solubility of the copper phthalocyanine core remain unchanged. The slightly lower average substitution grade does not alter the behaviour of the target substance in the eyes. It is considered to be non irritating without further testing.

A general read-across justification with data matrices are copied into the CSR.

 

Therefore, the criteria for classification and labelling as an eye irritant (GHS criteria) are not fulfilled.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin or eye irritation under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013.