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Toxicological information

Acute Toxicity: dermal

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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
Body weight:
Mean body weight of male and female animals was observed with gain on day 7 and 14 as compared to day 0
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.