7-(diethylamino)-4-methyl-2-benzopyrone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

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 the given test chemical 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
- Source and lot/batch No.of test material:FG/15-16/1865

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:

semiocclusive

Vehicle:

other: distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: the fur of dorsal area of the trunk
- % coverage: greater than 10% body surface area
- Type of wrap if used: Test item was held in contact with the skin with a porous gauze dressing (Approx. 10% of body surface area of rat) and non-irritating tape throughout a 24-hour exposure period. It was ensured that the animals cannot ingest the test item.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, residual test item was removed by using distilled water.
- Time after start of exposure:24-hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test item was applied uniformly over clipped dorsal area of rat skin.
- Concentration (if solution): Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2 ml distilled water

Duration of exposure:

24-hour

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 amle, 5 femlae

Control animals:

not specified

Details on study design:

Details on study design
- Duration of observation period following administration: 14 days (or other?): 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

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No effect on survival, Clinical Signs,Local Signs/Skin Reactions, Body Weight and gross pathology

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 acute dermal toxicity dose (LD50) was considered to be >2000 mg/kg bw, when male and female Wistar rats were treated with the given test chemical by dermal application over the clipped dorsal area of rat skin.

Executive summary:

The acute dermal toxicity study was conducted by using the given test chemical according to OECD Guideline 402 (Acute Dermal Toxicity) in 10 male and female Wistar rats at the concentration of 2000 mg/kg bw. The given test chemical (100% pure) was moistened with 0.2 ml distilled water and applied by single dermal application on intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed.The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1, 14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs/Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were recorded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period.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 2000 mg/kg body weight of test item during the experimental period.Mean body weight of male and female animals was observed with gain on day 7 and 14 as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

Therefore, the acute dermal toxicity dose (LD50) was considered to be >2000 mg/kg bw, when male and female Wistar rats were treated with the given test chemical by dermal application over the clipped dorsal area of rat skin. Thus, comparing this value with the criteria of CLP regulation, it cannot be classified for acute dermal toxicity.