Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, [[3-(cyclohexylamino)propyl]amino]sulfonyl derivs.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2018-01-03 to 2018-01-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

1

Reference substance name:

Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, [[3-(cyclohexylamino)propyl]amino]sulfonyl derivs.

EC Number:

309-627-7

EC Name:

Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, [[3-(cyclohexylamino)propyl]amino]sulfonyl derivs.

Cas Number:

100545-46-8

Molecular formula:

C32H16-τN8Cu.(SO3)m.(SO3H)p.(C9H19N2SO2)O.(C9H20N2SO2)n

IUPAC Name:

Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, [[3-(cyclohexylamino)propyl]amino]sulfonyl derivs.

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

SPF Caw

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Supplied by Elevage JANVIER LABS (53940 Le Genest St Isle – France)

- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 week old
- Weight at study initiation: 187-211 g

- Fasting period before study: day -1 and until 4 hours after the test item administration.

- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.

- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 h dartk/ 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2.0003 g of test item for the first step and 2.000 g of test item for the second step, in 10 mL volumetric flask filled up with DMSO.
- Amount of vehicle (if gavage): 10 ml/kg bw of preparation
- Justification for choice of vehicle: Dimethyl sulfoxide (DMSO) was chosen as it produced the most suitable formulation at the requested concentration.

Doses:

Step 1: 2000 mg/kg bw of test item
Step 2: 2000 mg/kg bw of test item

No. of animals per sex per dose:

3 females per dose per step.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations: The first day : at 30 min, 1h, 3h, 4h, 24h, then daily.
Weighing on D0 (prior administration), D2, D7 and D14.

- Necropsy of survivors performed: yes. Animals were euthanized with sodium pentobarbital (Dolethal®).
Only those organs likely to be modified in cases of acute toxicity were examined.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Macroscopic examinations at the end of the study (after euthanisia) with the examination of organs likely to be modified in cases of acute toxicity (i.e. oesophagus, stomach, the entire digestif tract, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, ovaries, uterus, treatment area,adrenals, pancreas).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the study

Clinical signs:

other: No clinical signs related to the administration of the test item were observed during the study.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight. In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat. The test item does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures. No signal word or hazard statement is required.

Executive summary:

The test item was administered to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight.

The experimental protocol was established according to O.E.C.D. Test Guideline No. 423 dated 17 December 2001 concerning acute oral toxicity and the test method B.1tris of Council regulation No.440/2008 dated 30 May 2008.

No mortality occurred during the study.

No clinical signs related to the administration of the test item were observed during the study.

The body weight evolution of the animals remained normal during the study.

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

In conclusion, the LD50 of the test item is higher than 2000 mg/kg body weight.

In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

The test item does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

No signal word or hazard statement is required.