Registration Dossier

Administrative data

Description of key information

Oral: LD50 (rat) > 6400 mg/kg bw (pre-GLP study similar to OECD TG 401)

Dermal: LD50 (rat) > 5000 mg/kg bw (non-GLP study accroding to OECD TG 402)


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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Meets generally accepted scientific standards, well documented study with the following restriction: In some cases in the highest dose group the application volume per animal slightly exceeded the volume of 2 ml/100 g bw, which is recommended in OECD guideline 401 as maximum application volume for aqueous solutions.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
BASF-Test:
In principle, the methods described in the OECD Guideline 401 were used. Young adult laboratory rats were purchased from breeder. Several groups of 5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 14 day study period. The LD50 value was estimated on the basis of the observed mortalities.
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Analytical purity: 100 %
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Firma Gassner, Ottobrunn; SPF breeding
- Average weight at study initiation: males: ca. 170 g; females: ca. 145 g
- Diet: Altromin-R (Altrogge, Lage/L., Germany), ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
Concentration of the test material in vehicle:
- 30 % (6400 and 3200 mg/kg bw)
- 16 % (1600 mg/kg bw),
- 2 % (200 mg/kg bw)

Amount of test material applied per gavage:
- 21.3 ml/kg bw for 6400 mg/kg bw;
- 10.6 ml/kg bw for 3200 mg/kg bw;
- 10.0 ml/kg bw for 1600 mg/kg bw;
- 10.0 ml/kg bw for 200 mg/kg bw
Doses:
200, 1600, 3200, 6400 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed and examined for clinical signs of toxicity during the first hour following application, after 4 hours and further on day 1, 4, 5, 6, 7, 8, 11, 12, and 13 after dosing.
- The body weights of the individual animals were gathered prior to application of the test material.
- Necropsy of survivors performed: yes. Deceased animals and those sacrificed at the end of the observation period (on day 14 after dosing) were necropsied.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 400 mg/kg bw
Mortality:
No mortality was observed at any dose group.
Clinical signs:
- 6400 - 3200 mg/kg bw:
Ca. 4 hours after application the animals were found in a crouched down position with intermittent breath. On the following morning slight apathy,a crouched down position and intermittent breath were observed. The stool of the animals was bluish discoloured until day 4. On the following days the animals were without any findings.
- 1600 - 200 mg/kg bw:
Immediately after application, irregular breath and masticatory movement were observed, after 4 hours the animals were found in a crouched down position. On the following days until day 3, the stool of the animals was bluish discoloured but later on the animals were without any findings.
Body weight:
The body weights of the individual animals were gathered prior to application of the test material only. No further documentation of body weight data was available.
Gross pathology:
Autopsy revealed no relevant findings.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the BASF test (similar to OECD guideline 401) for acute toxicity after oral application, the LD50 for the test material is > 6400 mg/kg body weight for male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
6 400 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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
non-GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Analytical purity: 100 %

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeding Farm VELAZ
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 236-278 g
- Housing: individually in plastic breeding cage Velaz T4
- Diet: DOS 2b - standard pelleted diet, ad libitum
- Water: drinking tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30-70 %
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The amount of the test substance for each animal was weighed (acc. to its body weight) and moistened with water for injection immediately before application.
Approx. 24 h before application of the test substance, the fur on the back of the animals was shaved at area about 6 cm x 6 cm.
Aliquot part of the test material was applied on the depilated area of skin. The application site was covered by mull, plastic foil and held in contact by plaster (strapping). After 24 h the occlusive dressing and the remains of the test substance were removed.
Duration of exposure:
24 h
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 males
Control animals:
no
Details on study design:
Body weight:
Animals were weighed before application, at 8th day and before euthanasia of animals. Average body weight in a group was calculated from individual body weights.

Clinical examination:
After application of the test material the animals were observed individually. Observations included changes of health conditions. Observations were performed daily during the 14 days observation period.

Pathological examination:
All test animal survivors to the end of the study were sacrificed on the 15th day and gross necropsy was carried out. Normally the nutritious state, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
All animals survived the 14 day observation period and the day of sacrifice.
Clinical signs:
No clinical signs of toxicity were observed during the study period.
Body weight:
Body weight gains were within the the physiological range.
Gross pathology:
No individual records of macroscopic changes were found.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Additional information

Oral:

There are valid data available for the assessment of the acute oral toxicity of test substance. Five male and five female Sprague-Dawley rats were treated with 200, 1600, 3200, 6400 mg/kg bw under standardized conditions; the test method is comparable to OECD guideline 401. The animals were observed for 14 d, necropsy was performed even with the survivors. The LD50 was > 6400 mg/kg bw for male and female rats. No mortality was observed at any dose group and autopsy revealed no relevant findings. Clinical signs were reported for all groups. In the 6400 - 3200 mg/kg bw groups, ca. 4 hours after application the animals were found in a crouched down position with intermittent breath. On the following morning slight apathy, a crouched down position and intermittent breath were observed. The stool of the animals was bluish discoloured until day 4. On the following days the animals were without any findings. In the 1600 - 200 mg/kg bw groups, immediately after application, irregular breath and masticatory movement were observed, after 4 hours the animals were found in a crouched down position. On the following days until day 3, the stool of the animals was bluish discoloured but later on the animals were without any findings (BASF AG, 1971).

In another supporting study, conducted with five male and five female mice per group, the animals were treated with 0 or 16000 mg/kg bw under standardized conditions and were observed for 14 d, necropsy was performed with all animals. The LD50 was > 16000 mg/kg bw for male and female mice. No mortality was observed and autopsy revealed no relevant findings. The following clinical signs were reported shortly after dosing in all treated mice: pilo-erection and abnormal body carriage (hunched posture) and abnormal gait (waddling). These findings were accompanied by lethargy (4 animals), ptosis (1 animal), diarrhoea, coloured blue (1 animal). Recovery of all treated mice as judged by external appearance and behaviour, was apparently complete within 4 days of dosing (Huntingdon 1981, Val. 2).

Other studies with partially limited reliability provided a LD50 range of > 10000 to > 15000 mg/kg bw in rats (Kurlandsky 1984, Val. 4; Webb 1984 Val. 4), the LD 50 value for another common test species (mouse) was > 10000 mg/kg bw (Gosselin 1976, Val. 4).

Dermal

There are valid data available for the assessment of the acute dermal toxicity of Copper phthalocyanine. Five male Wistar rats were treated with 5000 mg/kg bw under standardized conditions; the test method was acc. to OECD guideline 401 (limit test). The animals were observed for 14 d, necropsy was performed even with the survivors. The LD50 was > 5000 mg/kg bw for male rats. No mortality was observed, autopsy revealed no relevant findings and no clinical signs of toxicity were reported. Body weight gain was within the normal range (Synthesia 2009, Val. 2).

 

Justification for classification or non-classification

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 toxicity under Regulation (EC) No. 1272/2008, as amended for the 13th time in Regulation (EU) 2018/1480.