Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
data is from experimental reports

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
To assess the toxicological profile of the test chemical on application as a single semi-occlusive dermal application to rats
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Name of the test chemical: 3-nitrobenzoic acid
Molecular Formula: C7H5NO4
Molecular Weight: 167.1195 g/mol
SMILES: c1(cc(ccc1)[N+](=O)[O-])C(=O)O
Substance Type: Organic
Physical State: Solid

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
Details on test animals
Sex: females, Females were nulliparous and non-pregnant
Source :Vivo Bio Tech Ltd, Gajwel Mandal, Medak District, Telangana
Age at treatment: 8 to 10 weeks
Body weight range at treatment: Females: 213.42 to 248.13 g
Identification :By rat accession number. Identification of individual rats is by cage card and crystal violet colour body markings. The temporary body marking during acclimatization period was done with crystal violet. The rat accession numbers were allotted during the course of the study and was included in raw data and reported.
Housing: Animals were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill having facilities for pelleted food and drinking water in polycarbonate bottle. Steam sterilized corn cob was used and changed once a week along with the cage.
Diet:Rat & Mice pellet feed, manufactured by Krishna Valley Agro Tech LLP, MIDC Kupwad block, Sangli, Maharashtra, was provided ad libitum to animals
Water: Purified water in polycarbonate bottles with stainless steel sipper tubes was provided ad libitum
Acclimatization:After physical examination for good health and suitability for experiment, the rats were acclimatized for six, eight, twelve and fourteen days before treatment for dose range finding and main study respectively under standard laboratory conditions. Animals were observed once daily during acclimatization period.

Environmental Conditions:
Temperature: temperature 20 to 24°C
Relative humidity: 57 to 67 %,
Air changes: Animals were housed under standard laboratory conditions, air conditioned with adequate fresh air supply (12.9 to 14.0 air changes/hour)
Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle
In Life dates: Start: 31 March, 2018 , End: 24 April, 2018

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
DRF G1 2000 mg/kgbw
Main G1 2000mg/kgbw

- Concentration (if solution): 2000 mg/kg (G2) was weighed on an aluminum foil and made into a paste by adding sufficient volume (about 0.5 mL) of Milli-Q water

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
Treatment site at was observed for erythema and edema at 24, 48 and 72 hours after removal of test item using the Draize criteria
Number of animals:
3- [1- DRF; 2- Main]
Details on study design:
TEST SITE
- Area of exposure: clipped skin of the torso
- % coverage: 10% of the body surface of the animal (semi-occlusive).
- Type of wrap if used: The area of application was covered with cotton gauze (size: Females: 8 x 5 cm of 6 ply) and it was secured in position by adhesive tape wound around the torso
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: After the 24 hours contact period, the dressing was removed and the applied area was washed with deionized water and wiped dry using clean towels

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. In addition, the treatment site was observed at 24, 48 and 72 hours after
removal of test item using the Draize criteria
SCORING SYSTEM:
- Method of calculation: Draize method

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There were no skin reactions at the site of application at 24, 48 and 72 hours after test patch removal (as per Draize method).
Other effects:
There were no clinical signs and pre-terminal deaths (mortality) observed during the study. All rats gained body weight throughout the observation period.

Any other information on results incl. tables

APPENDIX 1.      Individual test item application, clinical signs, skin reactionand necropsy findings

Dose range finding study

 

Group & Dose

(mg/kg

body weight)

Date and time of application

Rat

Number

S

e

x

Initial

Bwt

(g)

Quantity

(mg)

applied

Observations and skin reaction

Days

1

2

3

4

5

30 min

1 h

2 h

3 h 

4 h

5 h

6 h

*

Er

@

Ed

@

*

Er

@

Ed

@

*

Er

@

Ed

@

G1 and

2000

DRF

 

05 April 2018

and

10.13 AM

Rm8761

F

231.51

463

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

Group & Dose

(mg/kg

body weight)

Rat

Number

S

e

x

Observation

Necropsy

findings

Days

6

7

8

9

10

11

12

13

14

15

G1 and

2000

DRF

Rm8761

F

N

N

N

N

N

N

N

N

N

N

NAD

F: Female             N: Normal          h: hour    min: minutes                      NAD: No abnormality detected      Er: Erythema                      Ed: Edema  

Score 0: No Erythema / Edema       

    

*: Clinical signs; @: Skin scoring as per Draize method (approximately 24, 48 and 72 hours) after test patch removal

 

Main study

 

Group & Dose

(mg/kg

body weight)

Date and time of application

Rat

Number

S

e

x

Initial

Bwt

(g)

Quantity

(mg)

applied

Observations and skin reaction

Days

1

2

3

4

5

30

min

1 h

2 h

3 h

4 h

5 h

6 h

*

Er @

Ed @

*

Er @

Ed @

*

Er @

Ed @

G1 and

2000

Main

 

10 April 2018

and

10.18AM and 10.20 AM

Rm8762

F

248.73

497

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

Rm8763

F

213.42

427

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

Group & Dose

(mg/kg

body weight)

Rat

Number

S

e

x

Observations

Necropsy

findings

Days

6

7

8

9

10

11

12

13

14

15

G2 and

2000

Main

 

Rm8762

F

N

N

N

N

N

N

N

N

N

N

NAD

Rm8763

F

N

N

N

N

N

N

N

N

N

N

NAD

F: Female             N: Normal          h: hour    min: minutes                       NAD: No abnormality detected      Er: Erythema                       Ed: Edema  

Score 0: No Erythema / Edema          

*: Clinical signs; @: Skin scoring as per Draize method (approximately 24, 48 and 72 hours) after test patch removal

 

 

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Conclusions:
There was no skin reaction observed at test item applied area. The mean erythema and edema scores were 0.0 at all observation times. Hence, it was concluded that the test chemical was Non-Irritating to the skin of Wistar rats under the experimental conditions tested and classified as “Category-Not Classified” as per CLP Classification.
Executive summary:

A study was designed and conducted to determine the dermal reaction profile of the test chemical in Wistar rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.

1 female for the dose range finding study, followed by additional 2 females rats for main study.

Based on the individual body weight, the test item at the dose of 2000 mg/kg body weight was weighed on an aluminum foil and made as a paste in Milli-Q water and applied directly to the clipped skin (clipping was done approximately 24 hour prior to application) of the animal to cover about 10% of the body surface of the animal (semi-occlusive). The area of application was covered with cotton gauze (size: Females: 8 x 5 cm of 6 ply) and it was secured in position by adhesive tape wrapped around the torso. The test item contact period with the skin was for 24 hours.

After the 24 hours contact period, the adhesive tape and cotton gauge was removed and the applied area was washed with deionized water and wiped dry using clean towels.

All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test item using the Draize criteria. There were no clinical signs of toxicity and mortality.

There was no skin reaction observed at test item applied area. The mean erythema and edema scores were 0.0 at all observation times. Hence, it was concluded that the test chemical was Non-Irritating to the skin of Wistar rats under the experimental conditions tested and classified as “Category-Not Classified” as per CLP Classification.