[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]iron

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

The purpose of this study was to assess the Toxicological profile of test item to a single administration via oral route to Sprague Dawley rats. This study was designed to determine the acute toxicity at fixed dose levels by oral route of the test item.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]iron

EC Number:

205-047-2

EC Name:

[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]iron

Cas Number:

132-16-1

Molecular formula:

C32H16FeN8

IUPAC Name:

[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]iron

Details on test material:

- Name of test material (as cited in study report): [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]iron
- Substance type: Organic

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Test Item: [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]iron (CAS No. 132-16-1)
- Source of test material: Sustainability Support Services (Europe) AB, Sweden
- Batch No. of test material: LBBOI
- Manufacturing Date: 1-10-2016
- Expiration date of the lot/batch: 1-10-2018
- Purity test date: No data available
- Consistency: Solid powder

RADIOLABELLING INFORMATION (not applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Test Item and prepared formulation(s) were stored at ambient temperature.
- Stability under test conditions: No data available
- Solubility and stability of the test substance in the solvent/vehicle: No data available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data available

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was suspended in corn oil.The formulation was perpared fresh on the day of dosing.The test item was administered in the dose volume of 10ml/kg bw.
- Preliminary purification step (if any): No data available
- Final dilution of a dissolved solid, stock liquid or gel: No data available
- Final preparation of a solid: No data available

FORM AS APPLIED IN THE TEST (if different from that of starting material) : No data available

OTHER SPECIFICS:
Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used at the commencement of its dosing.
- Weight at study initiation: Body weight range was 194.6 to 208.0 grams.
Body weights at the start :
Female
Mean : 201.41 g (= 100 %)
Minimum : 194.6 g (- 3.38 %)
Maximum : 208.0 g (+ 3.27 %)
Total No. of animals : 12
- Identification: Each female rat was individually identified by the picric acid marking.
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 to 22.5 degree centigrade.
- Humidity (%): 55.1% to 58.7%
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 7-05-2018 to 26-05-2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg, 2000 mg/kg and 2000 mg/kg
- Amount of vehicle (if gavage): No data available
- Justification for choice of vehicle: No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.

DOSAGE PREPARATION (if unusual): No data available

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No data available

Doses:

Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 mg/kg
Dose Group II : 2000 mg/kg

No. of animals per sex per dose:

Three females were used at each step.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality and morbidity, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Body weights:
Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.

Gross Pathology:
Necropsy was performed on all animals at the end of the study period on day 15. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique.

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Statistics:

No data

Results and discussion

Preliminary study:

no data available

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

Group I
Step I :
Animals treated at the dose level of 300 mg/kg body weight resulted in reduced locomotor activity,ataxia gait, and test item colored feces with onset at 30 minutes to day 1 after the dosing. All animals survived through the study period of 14 days and were free of signs of toxicity on day 2 after dosing.

Group I
Step II :
Animals treated at the dose level of 300 mg/kg body weight resulted in reduced locomotor activity,ataxia gait, and test item colored feces with onset at 30 minutes to day 1 after the dosing. All animals survived through the study period of 14 days and were free of signs of toxicity on day 2 after dosing.

Group II
Step I :
Animals treated at the dose level of 2000 mg/kg body weight resulted in reduced locomotor activity,ataxia gait, and test item colored feces with onset at 30 minutes to day 1 after the dosing. All animals survived through the study period of 14 days and were free of signs of toxicity on day 3 to day 4 after dosing.

Group II
Step II :
Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days and were free of signs of toxicity on day 3 to day 4 after dosing.

Clinical signs:

other: Group I Step I : Animals treated at the dose level of 300 mg/kg body weight resulted in reduced locomotor activity,ataxia gait, and test item colored feces with onset at 30 minutes to day 1 after the dosing. All animals survived through the study period

Gross pathology:

Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.

Other findings:

No data available

Any other information on results incl. tables

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Female

Group I :   

Step No.	Dose mg/kg	Total Number of Animals	Observed Signs	Animal Nos.	Period of signs in days From - to	Mortality
I	300	3	Reduced locomotor activity	1	30 min. - 2 hours	0
			Ataxia gait	1	1 hrs. - 6 hours
			Test item colored feces	1	Day 1
			Reduced locomotor activity	2	30 min. - 2 hours	0
			Ataxia gait	2	2 hrs. - 6 hours
			Test item colored feces	2	Day 1
			Reduced locomotor activity	3	1 hr. - 2 hours	0
			Ataxia gait	3	2 hrs. - 6 hours
			Test item colored feces	3	Day 1

 

Group I :

Step No.	Dose mg/kg	Total Number of Animals	Observed Signs	Animal Nos.	Period of signs in days From - to	Mortality
I	300	3	Reduced locomotor activity	4	1 hr. - 4 hours	0
			Ataxia gait	4	2 hrs. - 6 hours
			Test item colored feces	4	Day 1
			Reduced locomotor activity	5	30 min. - 4 hours	0
			Ataxia gait	5	4 hrs. - 6 hours
			Test item colored feces	5	Day 1
			Reduced locomotor activity	6	1 hr. - 2 hours	0
			Ataxia gait	6	2 hrs. - 6 hours
			Test item colored feces	6	Day 1

 

Group II :

Step No.	Dose mg/kg	Total Number of Animals	Observed Signs	Animal Nos.	Period of signs in days From - to	Mortality
I	2000	3	Reduced locomotor activity	7	1 hr. - 6 hours	0
			Ataxia gait	7	2 hrs. - day 2
			Test item colored feces	7	Day 1 - day 2
			Reduced locomotor activity	8	30 min. - 6 hours	0
			Ataxia gait	8	30 min. -day 3
			Test item colored feces	8	Day 1 - day 2
			Reduced locomotor activity	9	30 min. - 6 hours	0
			Ataxia gait	9	30 min. - day 3
			Test item colored feces	9	Day 1 - day 2

 

Group II :

Step No.	Dose mg/kg	Total Number of Animals	Observed Signs	Animal Nos.	Period of signs in days From - to	Mortality
I	2000	3	Reduced locomotor activity	10	30 min. - 6 hours	0
			Ataxia gait	10	1 hrs. - day 3
			Test item colored feces	10	Day 1 - day 2
			Reduced locomotor activity	11	30 min. - 6 hours	0
			Ataxia gait	11	1 hr.- day 3
			Test item colored feces	11	Day 1 - day 2
			Reduced locomotor activity	12	1 hr. - 6 hours	0
			Ataxia gait	12	2 hr. - day 2
			Test item colored feces	12	Day 1

 

Table No.II

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Female

Group I :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	300	Mean	199.50	210.20	5.36	229.00	8.96	14.80
		± SD	6.01	6.37	0.18	6.13	1.93	1.85

 

 

Group I :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
II	300	Mean	203.83	215.97	5.95	232.27	7.54	13.95
		± SD	4.10	4.41	0.52	5.38	0.38	0.49

 

 

Group II :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	200.80	209.53	4.35	229.43	9.50	14.27
		± SD	3.36	3.32	0.296	2.30	0.68	0.78

 

 

Group II :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
II	2000	Mean	201.50	210.00	4.21	227.97	8.55	13.12
		± SD	3.90	4.89	0.55	6.11	0.42	0.88

 

 

Table No.III 

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Female

Group I :

 

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	300	1 - 3	TS	No abnormality detected

Group I :

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
II	300	4 - 6	TS	No abnormality detected

 

Group II :

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	7 - 9	TS	No abnormality detected

 

Group II : 

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
II	2000	10 - 12	TS	No abnormality detected

                      

TS = Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The acute oral LD50 of test chemical was considered to be >2000 mg/kg body weight, when administered via oral route in Sprague Dawley rats.

Executive summary:

The study now reported was designed and conducted to determine the acute oral toxicity profile of test chemical in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in diarrhoea, reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing and no mortality after the dosing. As no mortality was observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in diarrhoea, reduced locomotor activity and ataxic gait with onset at 2 to 4 hours after the dosing and no mortality after the dosing.

Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 of test chemical was >2000 mg/kg body weight. 

Thus, it was concluded that the acute toxicity study of Test chemical, when administered via oral route in Sprague Dawley rats which “not classified" as per criteria of CLP.