Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-), compound with dodecylamine (1:1)

Endpoint summary

Description of key information

In an acute oral toxicity study with rats (OECD 423, GL), the LD50 was >2000 mg/kg bw and no indication of toxicity was observed. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Age at study initiation: Young adult animals (female animals approx. 14- 18 weeks)
- Weight at study initiation: 185-213g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing: Single housing in stainless steel wire mesh cages, type DK-Ill (Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiät (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Acclimatization tor at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): fully airconditioned
- Photoperiod (hrs dark / hrs light): 12h/12h (6.00 a.m. - 6.00 p.m. / 6.00 p.m. - 6.00 a.m.)

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

Olive oil Ph.Eur./DAB

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20g / 100 mL
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: Inhomogeneous in watery preparations. Olive oil Ph.Eur./DAB had to be used to ensure homogeneity of the preparation.

DOSAGE PREPARATION: The test substance preparation was produced for each administration group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study
- Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Pathology: Necropsy with gross-pathology examination on the last day of the observation period after killing with CO2.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical observation revealed blue discolored feces and was observed from hour 3 until including hour 5 after administration.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: males: ca. 247 g; females: ca. 202 g
- Housing: 5 animals per cage in stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, Germany)
- Fasting period: the animals were given no feed 16 h before administration, but water was available ad libitum
- Diet: Kliba Labordiaet 343 (Klingentalmuehle AG, Kaiseraugst, Switzerland), ad libitum
- Water: ad libitum
- Acclimatization period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24 °C
- Humidity: 30-70 %
- Photoperiod: 12 hrs dark / 12 hrs light

Type of coverage:

semiocclusive

Vehicle:

other: 0.5 % aqueous carboxymethylcellulose

Details on dermal exposure:

- Concentration of the test material in vehicle: 50 %
- Amount of test material applied: 4 ml/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

A single application of the test material was applied on the clipped epidermis (dorsal and dorsolateral parts of the trunk), ca 50 cmxcm. The application site was covered with an semiocclusive dressing for 24 hours. Afterward the dressing was removed and the application site was rinsed with warm water.
The signs and symptoms of toxicity were recorded several times on the day of application, at least once each working day. A check for moribund and dead animals was conducted each working day and once on holidays.
30-60 min after removal of the semiocclusive dressing a scoring for skin findings was conducted, and again one week later and before termination of the study.
- The body weights of the individual animals were gathered prior to application of the test material and on day 7 and 13 after dosing.
- Necropsy of survivors performed: Deceased animals and those sacrificed at the end of the observation period (on day 14 after dosing) were necropsied. 16 h before sacrifice the food was withdrawed and the animals were sacrificed with CO2.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived, no mortality was observed.

Clinical signs:

other: No clinical signs of toxicity were seen in males or females. A local irritation index could not be read, because of staining due to the colour of the test material in males and females.

Gross pathology:

Autopsy revealed no relevant findings.

Table 1: Mean body weight (g) of rats after dermal application

	Males	Females
Dose level [mg/kg bw]	5000	5000
Day 7	277	207
Day 13	304	218

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

A GLP-compliant study, performed according to OECD guideline 423, was performed to assess the acute toxicity following oral administration of the test substance in Wistar rats. Single doses of 2000 mg/kg bw of test substance preparations in olive Ph.Eur./DAB were given to two administration groups ot three fasted female animais, by gavage in a sequential manner. No mortality occurred. ClinicaI observation revealed blue discolored feces. This finding was observed from hour 3 until including hour 5 after administration. The mean body weights of the administration groups increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period.

Under the conditions of this study the LD50 of the test substance after oral administration was found to be greater than 2000 mg/kg body weight in rats.

As outlined in the data waiving for the need of testing for acute dermal toxicity, no hazard is identified for acute dermal exposure.

For supporting evidence, a GLP-compliant acute dermal toxicity study following OECD testing guideline 402 with a structural analogue is presented. CAS 108300 -90 -9 has a higher degree of substituion (three versus 1) and therefore has a higher molecular weight. This makes it not suitable as stand-alone replacement. The analogue substance caused no systemic toxicity and no mortality in the acute dermal toxicity in rats at the limit dose of 2000 mg/kg bw. Scoring of local reactions was limited due to the blue staining by the test substance. This would however also have been observed for the target substance as it is also a blue colorant.

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 acute oral and dermal toxicity under Directive 67/548/EEC.

 

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 acute oral and dermal toxicity under Regulation (EC) No. 1272/2008.