Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, (1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)methyl derivs.

Endpoint summary

Description of key information

This UVCB substance is assessed as non hazardous for acute toxicity from experimental data in rats with another UVCB substance consisting of identical components. Both UVCB substances are poorly soluble nanomaterials.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

Higher doses tested; only 7 day observation period.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weight: males 241 g, females 176 g

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

Suspension in 0.5% aqueous CMC solution
Test concentration used: 35%

Doses:

4640 and 10000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Partly feces dark-blue coloured

Gross pathology:

Nothing abnormal detected

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

10 000 mg/kg bw

Quality of whole database:

Klimisch 2

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

It is referred to the attached document.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Species:

rat

Route of administration:

inhalation: dust

Sex:

male/female

Dose descriptor:

discriminating conc.

Effect level:

2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

2 mg/m³ air

Physical form:

inhalation: dust

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

according to D.N. Noakes and D.M. Sanderson: A Method for Determining the Dermal Toxicity of Pesticides; Brit. J. Ind. Med. 26, 59 (1969)

Deviations:

yes

Remarks:

higher dose; body weight not reported.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weight: males 148 g, females 131 g

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

A 50% test substance concentration was used.

Duration of exposure:

24 hours

Doses:

2500 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Application area: 50 cm2
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Mortality:

None

Clinical signs:

other: During and after application as well as after the 14-day observation period, the animals were brisk. Local findings after 24 hours: all animals blue test substance residues, reddening not visible. Local findings after 8 days: light-blue substance residues

Gross pathology:

Nothing abnormal detected

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Quality of whole database:

Klimisch 2

Additional information

The substance itself was not tested for acute toxicity. Experimental data is available for the analogue UVCB substance CAS 559160 -79 -1 which only differs from the target substance by an higher average degree of substitution and consists of the same components. For more information supporting the read-across it is referred to the attachment in the toxicokinetic section. It includes data matrices and chemical structures.

The experimental data

for the analogue UVCB substance CAS 559160 -79 -1

were generated prior to the introduction of GLP and OECD testing guidelines. Study reports containing adequate description of the experimental procedure and results and with adequate identification of the test substance are available.

The protocol for acute oral toxicity differs from the OECD testing guideline by the shorter observation period (7 instead of 14 days) and by a five-fold higher dose (10000 instead of 2000 mg/kg bw) (BASF 1976). Considering the lack of toxicity observed under these testing conditions, the study is considered to provide sufficient information despite the shorter oberservation period. Blue discoloration of the feces indicated passage of the blue colorant through the gastrointestinal tract.

The protocol for acute dermal toxicity differs from OECD testing guideline 402 by a higher dose of 2500 mg/kg bw. No systemic toxicity was observed during the 14 -day observation period. As the test item coloured the application site, local effects could only be partly assessed during the first part of the study. Then later no local effects were noted.

An acute inhalation study with poorly characterized dusty material in rats was performed (BASF 1976). The test atmosphere was generated by blowing air through a layer of the test material and the concentration was calculated from the weight difference of the layer of the test material. During the 8h exposure, an average concentration of ca. 5mg/L was applied. No particle size characterization and no online concentrations are available, therefore the study is only indicative. No rat died as a consequence of treatment.

A more recent acute inhalation toxicity study in rats with a phthalocyanine nanomaterial was performed in 2021.To determine the acute inhalation toxicity (single 4-hour exposure, nose only) of 29H,31Hphthalocyanine as a dust, a study was performed in male and female Wistar rats according to OECD-Guideline method 403, as well as EC and EPA guidelines (BASF 2021). The test was run with an actual measured concentration of 2.046 mg/L (analytical concentration).

Cascade impactor measurements resulted in particle size distributions with mass median aerodynamic diameters (MMADs) of 2.67 and 2.58 μm, which are well within the respirable range.

One of the five males died at 2.046 mg/L on study day 0 during exposure. The death was determined in the 2nd hour of the exposure. No mortality was observed in female animals. Clinical signs of toxicity in animals comprised abdominal and intermittent respiration, respiration sounds, hunched posture, piloerection, substance-contaminated and discolored fur substance like. Findings were observed from hour 1 of exposure until the end of the 14-day post-exposure observation period. The mean body weights of the surviving animals decreased on the first post-exposure observation day but increased thereafter. This is a typical finding for this test design. Gross necropsy of the male animal that died on study day 0 showed blue discoloration of the fur on the entire body. During necropsy of the surviving animals at the termination of the post-exposure observation period the following gross pathological findings were noted: many blue foci in all lung lobes, grey/blue discoloration of the mediastinal lymph nodes and blue discoloration of the fur of the tail and/or head region. To further evaluate the macroscopic findings, histopathological examination was carried out of the respiration tract from the male animal No. 721 which died on study day 0. Minimal amount of green-blue crystals revealing the presence of the test substance were seen in the lumen of the larynx, pharynx and nasal cavity. Furthermore, in the larynx, slight grey granular material in the lumen and a slight edema in the region of the ventral pouch were noted. All these findings are regarded as treatment-related, however they are not considered relevant enough to explain the death of this animal.

Under the current study conditions, the LC50value was > 2.046 mg/L in male and female Wistar rats after a 4-hour inhalation exposure to the dust aerosol of 29H,31H-phthalocyanine.

In addition,for the analogue UVCB substance CAS 559160 -79 -1

a study with intraperitoneal application of 2000 mg/kg bw is available (BASF 1976). No animal died during the 8 -day observation period.

In all studies, effects were clearly absent and far away from any threshold of classification and labelling. There is no uncertainty of read-across arising from the nature or the severety of the effects.

Justification for classification or non-classification

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. The LD50 is greater than 2000 mg/kg bw. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the fifthteens time in Directive EC 2020/1182.