2,2'-(vinylenedi-p-phenylene)bisbenzoxazole

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:

2017

Report date:

2017

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:

2,2'-(vinylenedi-p-phenylene)bisbenzoxazole

EC Number:

216-245-3

EC Name:

2,2'-(vinylenedi-p-phenylene)bisbenzoxazole

Cas Number:

1533-45-5

Molecular formula:

C28H18N2O2

IUPAC Name:

2,2'-(ethene-1,2-diyldi-4,1-phenylene)bis(1,3-benzoxazole)

Test material form:

solid: crystalline

Details on test material:

SOURCE OF TEST MATERIAL
- Test Item: 2,2’-(vinylenedi-p-phenylene)bisbenzoxazole (CAS No. 1533-45-5)
- Source of test material: Sustainability Support Services (Europe) AB
- Batch No.of test material: OBA201405A
- Manufacturing Date: October 2016
- Expiration date of the lot/batch: October 2019
- Consistency: Solid, crystalline powder

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient Temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was suspended in corn oil. The formulation was prepared fresh on the day of dosing. The test item was administered in the dose volume of 10 ml/kg body weight. Actual preparation procedures are documented in the raw data.

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 206.6 grams.
Body weights at the start : Female Mean : 199.49 g (= 100 %); Minimum : 194.6 g (- 2.45 %); Maximum : 206.6 g (+ 3.56 %)
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): 20.4 to 22.0 degree centigrade.
- Humidity (%): 53.1% to 58.5%.
- 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: 01-06-2017 to 20-06-2017

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

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:

not specified

Results and discussion

Preliminary study:

not specified

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 : All animals survived through the study period of 14 days.
Group I Step II : All animals survived through the study period of 14 days.
Group II Step I : All animals survived through the study period of 14 days.
Group II Step II : All animals survived through the study period of 14 days.

Clinical signs:

other: Group I Step I : Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. Group I Step II : Animals treated at the dose level of 300 mg/kg body weight did not result in any s

Gross pathology:

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

Other findings:

not specified

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	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
I	300	No clinical signs observed	3	1,2,3	Day 0 - Day 14	0/3

  

Group I :

Step No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
II	300	No clinical signs observed	3	4,5,6	Day 0 - Day 14	0/3

 

Group II :

Step No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
I	2000	No clinical signs observed	3	7,8,9	Day 0 - Day 14	0/3

 

Group II :

Step No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
II	2000	No clinical signs observed	3	10,11, 12	Day 0 - Day 14	0/3

 

 

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	198.80	213.50	7.40	225.83	5.78	13.60
		± SD	1.90	2.20	0.85	2.35	0.22	1.10

 

 

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	202.53	216.87	7.08	229.20	5.70	13.19
		± SD	4.44	3.69	0.53	2.30	0.77	1.37

 

 

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	196.67	211.87	7.73	226.23	6.78	15.04
		± SD	1.92	2.25	0.18	2.06	0.46	0.60

 

 

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	199.97	214.77	7.41	229.60	6.91	14.82
		± SD	2.31	1.72	0.77	1.83	0.08	0.92

 

 

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 lethal concentration (LD50) value for acute oral toxicity test was considered to be >2000 mg/kg bw, when female Sprague Dawley rats were treated with the given test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Executive summary:

The acute oral toxicity profile of the given test chemical in female Sprague Dawley rats according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

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 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 did not result in any signs of toxicity and mortality after the dosing. As no mortality were 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 did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. 

Therefore, the lethal concentration (LD50) value for acute oral toxicity test was considered to be >2000 mg/kg bw, when female Sprague Dawley rats were treated with the given test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).