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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 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:
other: liquid/ crystalline mass
Details on test material:
- Name of test material: 2-Propen-1-ol, 3-phenyl-;cinnamyl alcohol;
- Molecular formula: C9H10O
- Molecular weight: 134.177g/mole
- Smiles : c1(ccccc1)/C=C/CO
- Inchl: 1/C9H10O/c10-8-4-7-9-5-2-1-3-6-9/h1-7,10H,8H2/b7-4-
- Substance type: Organic
- Physical state: liquid/ crystalline mass

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
Detailas on test animals and environmental conditions:

Sex: females, Females were nulliparous and non-pregnant
Source : Geniron Biolabs Pvt. Ltd., Bengaluru, India
Age at treatment: 11 to 12 weeks
Body weight range at treatment: Females: 211.56 to 231.27 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. Additionally, polycarbonate rat huts were placed inside the cage as enrichment objects and were changed along with the cage once a week.
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, 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, ten and twelve days before treatment for dose range finding studies and main study respectively under standard laboratory conditions. Animals were observed once daily during acclimatization period.

Environmental Conditions:
Temperature: 22 to 24°C
Relative humidity: 66 to 68%
Air changes: air conditioned with adequate fresh air supply (13.0 air changes/hour)
Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle

Test system

Type of coverage:
occlusive
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 (2 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

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
14 d
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
14 d
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. No abnormality was detected at necropsy.

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

(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

 

24 April 2018

and

10.41 AM

Rm9127

F

231.27

0.05

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

 

Rm9127

F

N

N

N

N

N

N

N

N

N

N

NAD

F: Female             N: Normal          h: hour    min: minutes       DRF: Dose Range Finding           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

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

@

G2 and

1000

DRF

 

26 April 2018

and

10.40 AM

Rm9128

F

218.19

0.22

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

G2 and

1000

DRF

 

Rm9128

F

N

N

N

N

N

N

N

N

N

N

NAD

F: Female             N: Normal          h: hour    min: minutes       DRF: Dose Range Finding               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

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

@

G3 and

2000

DRF

 

28 April 2018

and

10.43 AM

Rm9129

F

211.56

0.42

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

G3 and

2000

DRF

Rm9129

F

N

N

N

N

N

N

N

N

N

N

NAD

F: Female             N: Normal          h: hour    min: minutes       DRF: Dose Range Finding               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

(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 @

G3 and

2000

Main

 

30 April 2018

and

11.01AM to 11.02 AM

Rm9130

F

214.99

0.43

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

Rm9131

F

213.42

0.43

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

G3 and

2000

Main

 

Rm9130

F

N

N

N

N

N

N

N

N

N

N

NAD

Rm9131

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.

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 (2 mL/kg body weight) - based on the density of the test item1.01 g/cm3(as per TIDS) was applied directly to the clipped skin of the animal to cover about 10% of the body surface of the animal (semi-occlusive). The applied area 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 towel. 

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.