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Toxicological information

Skin irritation / corrosion

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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 report

Data source

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

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
12H-phthaloperin-12-one
EC Number:
230-049-5
EC Name:
12H-phthaloperin-12-one
Cas Number:
6925-69-5
Molecular formula:
C18H10N2O
IUPAC Name:
12H-isoindolo[2,1-a]perimidin-12-one
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material : 12H-phthaloperin-12-one
- Common name : C.I. Solvent Orange 60
- Molecular formula : C18H10N2O
- Molecular weight : 270.29 g/mol
- Smiles notation : O=C1N2c3c4c(cccc4N=C2c2ccccc12)ccc3
- InChl : 1S/C18H10N2O/c21-18-13-8-2-1-7-12(13)17-19-14-9-3-5-11-6-4-10-15(16(11)14)20(17)18/h1-10H
- Substance type : Organic
- Physical state : Solid

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
Details on test animals
Sex: females, Females were nulliparous and non-pregnant
Source : Geniron Biolabs Pvt. Ltd., Bengaluru, India
Age at treatment: 10 to 12 weeks
Body weight range at treatment: Females: 235.18 to 238.33 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:Hypro Rat & Mice pellet feed, manufactured at Sangli, Maharashtra, was provided to 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: 22 to 25°C
Relative humidity: 66 to 68%
Air changes: air conditioned with adequate fresh air supply (12.4 air changes/hour)
Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle

In Life dates: Start: 26 June 2018 , End: 11 September 2018

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
Dose range finding study:200 (0.20 mL/kg body weight), 1000 (1 mL/kg body weight) and 2000(1.99 mL/kg body weight)
Main Study: 2000 mg/kg
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
5 females (3 females for dose range finding study followed by 2 females for main study)
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

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritation was observed.

Any other information on results incl. tables

TABLE 1.            Individual body weight, body weight changes and pre-terminal deaths

Group and

Dose

(mg/kg body weight)

Rat

No.

S

e

x

Body weight (g)

Pre-terminal deaths

Initial

(Day 1 - at treatment)

8th  

day

Weight change

(day 8 – Initial)

15th

day

Weight change

(day 15 – Initial)

G1 and

200

DRF

Rw283

F

235.18

242.68

7.50

248.19

13.01

0

G2 and

1000

DRF

Rw284

F

238.33

245.45

7.12

251.67

13.34

0

G3 and

2000

DRF

Rw285

F

238.16

244.73

6.57

249.14

10.98

0

G3 and

2000

Main study

Rw286

F

230.34

236.59

6.25

241.08

10.74

0

Rw287

F

234.62

242.93

8.31

247.63

13.01

0

 DRF: Dose Range Finding   F: Female

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

(mL)

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

200

DRF

11 April 2018

and

10.55 AM

Rm8907

F

223.58

0.04

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

200

DRF

Rm8907

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

 

 

APPENDIX 2 contd. Individual test item application, clinical signs, skin reaction and 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

30

 min

1 h

2 h

3 h 

4 h

5 h

6 h

*

Er

@

Ed

@

*

Er

@

Ed@

G1- DRF

 and

200

 

03 July 2018

and

11.36 AM

Rw283

F

235.18

47

N

N

N

N

N

N

N

N

N

0

0

N

0

0

Group & Dose

(mg/kg

body weight)

Animal

Number

S

e

x

Observation/ Days

Necropsy

findings

5

 

*

Er

@

Ed

@

6

7

8

9

10

11

12

13

14

15

G1- DRF

 and

200

 

Rw283

F

N

0

0

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

APPENDIX 2 contd. Individual test item application, clinical signs, skin reaction and 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

30

 min

1 h

2 h

3 h

4 h

5 h

6 h

*

Er

@

Ed

@

*

Er

@

Ed

@

G2- DRF

 and

1000

 

05 July 2018

and

11.56 AM

Rw284

F

238.33

238

N

N

N

N

N

N

N

N

N

0

0

N

0

0

Group & Dose

(mg/kg

body weight)

Animal

Number

S

e

x

Observation/ Days

Necropsy

findings

5

 

*

Er

@

Ed

@

6

7

8

9

10

11

12

13

14

15

G2- DRF

 and

1000

 

Rw284

F

N

0

0

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

 

 

APPENDIX 2 contd. Individual test item application, clinical signs, skin reaction and necropsy findings

 

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

30

min

1 h

2 h

3 h

4 h

5 h

6 h

*

Er @

Ed @

*

Er @

Ed @

G3- Main

and

2000

 

12 July 2018

and

11.41 AM to 11.42 AM

Rw286

F

230.34

461

N

N

N

N

N

N

N

N

N

0

0

N

0

0

Rw287

F

234.62

469

N

N

N

N

N

N

N

N

N

0

0

N

0

0

 

Group & Dose

(mg/kg

body weight)

Animal

Number

S

e

x

Observation/ Days

Necropsy

findings

5

 

*

Er

@

Ed

@

6

7

8

9

10

11

12

13

14

15

G3- Main

 and

2000

 

Rw286

F

N

0

0

N

N

N

N

N

N

N

N

N

N

NAD

Rw287

F

N

0

0

N

N

N

N

N

N

N

N

N

N

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 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:

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

The test chemical was tested in 5 females (3 females for dose range finding study followed by 2 females for main study) Wistar rats at the doses of 200, 1000 and 2000 mg/kg body weight.

Based on the individual body weight, the undiluted test item at the doses of 200 (0.20 mL/kg body weight), 1000 (1 mL/kg body weight) and 2000(1.99 mL/kg body weight) - based on the density of the test item1.004 g/cm3 was applied directly to the clipped skin 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 wound around the torso. The test item contact period with the skin was for 24 hours. 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. 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. Body weight was measured on days 1, 8 and 15 and all rats gained weight during experimental period. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the necropsy.

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.