2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]-1,3-dimethyl-1H-benzimidazolium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Dermal toxicity of 2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl] benzoxazole-5-sulphonamide (CAS No. 68427-35-0) after single dose application by dermal route in rats and an observation period of 14 days.

GLP compliance:

yes

Test type:

other: Acute dermal Toxicity

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazole-5-sulphonamide

EC Number:

270-393-3

EC Name:

2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazole-5-sulphonamide

Cas Number:

68427-35-0

Molecular formula:

C20H19N3O5S

IUPAC Name:

2-[7-(diethylamino)-2-oxo-2H-chromen-3-yl]-1,3-benzoxazole-5-sulfonamide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material : 2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl] benzoxazole-5-sulphonamide
- Molecular formula : C20H19N3O5S
- Molecular weight :413.452 g/mole
- Substance type: Organic
- Physical state:Powder
- Source and lot/batch No.of test material:FG/15-16/1865

Specific details on test material used for the study:

- Name of test material : 2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl] benzoxazole-5-sulphonamide
- Molecular formula : C20H19N3O5S
- Molecular weight :413.452 g/mole
- Substance type: Organic
- Physical state:Powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-House Bred at sa-FORD, Animal Facility (CPCSEA Registration No. 1256/bc/09/CPCSEA)
- Age at study initiation: No data available
- Weight at study initiation: Male:Minimum: 240 g and Maximum: 280 g , Female:Minimum: 222 g and Maximum: 239 g
- Fasting period before study:No data available
- Housing: Animals were housed three per polycarbonate cage of size 37 [cm] x 21 [cm], height 20 [cm] and identified by toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number experimental start date, dosing date and completion date.
- Diet (e.g. ad libitum): conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No: 040316., ad libitum
- Water (e.g. ad libitum): Aqua guard filtered tap water, ad libitum
- Acclimation period:7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.80 °C - Maximum: 22.80 °C
- Humidity (%):Minimum: 47.10% - Maximum: 68.60%
- Air changes (per hr):12 hour light and 12 hour dark
- Photoperiod (hrs dark / hrs light):More than 12 changes per hour

IN-LIFE DATES: From: April 19, 2016
To:May 03, 2016

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: the fur of dorsal area of the trunk of rats was clipped by using clipper.
- % coverage: greater than 10% body surface area
- Type of wrap if used: a porous gauze dressing and non-irritating tape

Details on exposure:
VEHICLE
- Concentration in vehicle: 2000 mg/kgbw
- Amount of vehicle (if gavage): 0.2 ml
- Justification for choice of vehicle:No data available
- Lot/batch no. (if required):No data available
- Purity:No data available

MAXIMUM DOSE VOLUME APPLIED:2000 mg/kgbw

Duration of exposure:

24 hour

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 male, 5 female

Control animals:

not specified

Details on study design:

Details on study design
- Duration of observation period following administration: 14 day observation period
- Frequency of observations and weighing: at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing) and once a day during the 14 day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Yes

Statistics:

No statistical analysis was performed since the study was terminated with limit test

Results and discussion

Preliminary study:

no data available

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period

Clinical signs:

other: No systemic signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period No local signs of toxicity (e.g.: Abrasion, Alopecia, Erythema, Oedema, Scale Formation etc.) were observed at limit dose of 2

Gross pathology:

The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality

Other findings:

No data available

Any other information on results incl. tables

Individual Animal Mortality Record

Animal No.	Sex	Days of Observation (0 to 14)
		Morning Observations	Evening Observations
01	Male	No mortality and morbidity	No mortality and morbidity
02		No mortality and morbidity	No mortality and morbidity
03		No mortality and morbidity	No mortality and morbidity
04		No mortality and morbidity	No mortality and morbidity
05		No mortality and morbidity	No mortality and morbidity
06	Female	No mortality and morbidity	No mortality and morbidity
07		No mortality and morbidity	No mortality and morbidity
08		No mortality and morbidity	No mortality and morbidity
09		No mortality and morbidity	No mortality and morbidity
10		No mortality and morbidity	No mortality and morbidity

Summary of Animal Body Weight (g) and Body Weight Changes (%)

Sex		Body Weight (gram)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
Male	Mean	261.60	273.00	298.40	4.33	14.09
	SD	16.68	19.20	20.03	1.35	3.60
	n	5	5	5	5	5
Female	Mean	229.60	232.40	246.00	1.21	7.14
	SD	7.13	8.02	8.92	0.70	1.45
	n	5	5	5	5	5

Gross Necropsy Observation

Animal No.	Sex	Gross Observation
		External	Internal
01	Male	No abnormality detected	No abnormality detected
02		No abnormality detected	No abnormality detected
03		No abnormality detected	No abnormality detected
04		No abnormality detected	No abnormality detected
05		No abnormality detected	No abnormality detected
06	Female	No abnormality detected	No abnormality detected
07		No abnormality detected	No abnormality detected
08		No abnormality detected	No abnormality detected
09		No abnormality detected	No abnormality detected
10		No abnormality detected	No abnormality detected

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was considered to be > 2000 mg/kg bw when Wistar male and female rats were treated with 2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl] benzoxazole-5-sulphonamide.

Executive summary:

In a acute dermal toxicity study, Wistar male and female rats treated with 2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl] benzoxazole-5-sulphonamide in the concentration of 2000 mg/kg bw orally by gavage as per OECD 402 and observed for 14 days. No effect on survival, clinical sign and  Local Signs/Skin Reactions were observed in treated male and female rats. Gain in body weight were observed on day 7 and 14, as compared to day 0 body weight, weighed prior to dosing in 2000 mg/kg bw treated male and female rats. In addition, No external and internal gross pathological abnormalities were observed in 2000 mg/kg bw treated male and female rats. Therefore, LD50 value was > 2000 mg/kg body weight when Wistar male and female rats treated with 2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl] benzoxazole-5-sulphonamide orally by gavage.