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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
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:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The objective of this acute dermal toxicity study was to assess the toxicological profile of the test item on application as a single semi-occlusive dermal application to rats.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-phenylethanol
EC Number:
202-707-1
EC Name:
1-phenylethanol
Cas Number:
98-85-1
Molecular formula:
C8H10O
IUPAC Name:
1-phenylethanol
Details on test material:
- IUPAC Name: 1-phenylethan-1-ol
- Common Name: 1-Phenylethanol
- InChI: 1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3
- Smiles: c1(ccccc1)C(C)O
- Molecular formula :C8H10O
- Molecular weight :122.166 g/mol
- Substance type:Organic
- Physical state:Clear colourless liquid
- Purity as per Certificate of Analysis:99.8%
- Lot No.:10207187
- Manufactured date:20 June 2017
- Retest date:20 June 2027
- pH:4.44
- Density:1.004 g/cm3 at 30°C
- Storage conditions:Ambient (+18 to +36°C)
- SAFETY PRECAUTIONS: Gloves, cap and face mask were used in addition to protective body garments and shoes, to ensure adequate personal health and safety and to avoid inhalation and skin contact with the test item.
- Preparation: 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 item 1.004 g/cm3 (as per TIDS provided by the sponsor) was applied directly to the clipped skin of the animal (semi-occlusive)
Specific details on test material used for the study:
- IUPAC Name: 1-phenylethan-1-ol
- Common Name: 1-Phenylethanol
- InChI: 1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3
- Smiles: c1(ccccc1)C(C)O
- Molecular formula :C8H10O
- Molecular weight :122.166 g/mol
- Substance type:Organic
- Physical state:Clear colourless liquid
- Purity as per Certificate of Analysis:99.8%
- Lot No.:10207187
- Manufactured date:20 June 2017
- Retest date:20 June 2027
- pH:4.44
- Density:1.004 g/cm3 at 30°C
- Storage conditions:Ambient (+18 to +36°C)
- SAFETY PRECAUTIONS: Gloves, cap and face mask were used in addition to protective body garments and shoes, to ensure adequate personal health and safety and to avoid inhalation and skin contact with the test item.
- Preparation: 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 item 1.004 g/cm3 (as per TIDS provided by the sponsor) was applied directly to the clipped skin of the animal (semi-occlusive)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd. Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: Females: 213.88 to 223.58 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. Additionally, polycarbonate rat huts were placed inside the cage as enrichment objects and were changed along with the cage once a week. Bedding: Steam sterilized corn cob was used and changed once a week along with the cage.
- Diet (e.g. ad libitum): Hypro Rat & Mice pellet feed, ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier, ad libitum
- Acclimation period: 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 25°C
- Humidity (%): 66 to 68%
- Air changes (per hr): 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: From: 05 April 2018 To: 03 May 2018

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of dorsolateral thoracic surface
- % coverage: 10% of the body surface
- Type of wrap if used: 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.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the applied area was washed with deionized water and wiped dry using clean towel.
- Time after start of exposure:24 hours
Duration of exposure:
24 hours
Doses:
DRF G1 - 200 mg/kg
DRF G2 - 1000 mg/kg
DRF G3 - 2000 mg/kg
Main G3 - 2000 mg/kg
No. of animals per sex per dose:
DRF G1 - 200 mg/kg - 1
DRF G2 - 1000 mg/kg - 1
DRF G3 - 2000 mg/kg - 1
Main G3 - 2000 mg/kg - 2
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical examination and pre-terminal deaths - The animals were observed for clinical signs and pre-terminal deaths (mortality) once during first 30 minutes after application, and at hourly intervals for 6 hours after application on the day of treatment (day 1) and once daily during Days 2 to 15. In addition, the treatment site was observed for skin reactions at 24, 48 and 72 hours after removal of test chemical using the Draize criteria (Refer Annexure 4 of this report). All rats were observed for changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weights - Individual body weights of animals were recorded on test days 1(Pre-application), 8 (7 days post application), and 15 (14 days post application).
- Necropsy of survivors performed: yes, at the end of the observation period, all rats were euthanised and exsanguinated under isoflurane anesthesia and subjected to detailed necropsy by an experienced prosector and the findings were recorded.
- Other examinations performed: Microscopic examination was not carried out as no gross pathological changes were observed.
Statistics:
not specified

Results and discussion

Preliminary study:
not specified
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no pre-terminal deaths (mortality) observed during the study.
Clinical signs:
There were no clinical signs observed during the study.
Body weight:
All rats gained body weight throughout the observation period.
Gross pathology:
No abnormality was detected at necropsy.
Other findings:
not specified

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

Rm8907

F

223.58

228.46

4.88

234.42

10.84

0

G2 and

1000

DRF

Rm8908

F

217.14

222.02

4.88

230.19

13.05

0

G3 and

2000

DRF

Rm8909

F

220.12

224.34

4.22

229.66

9.54

0

G3 and

2000

Main study

Rm8910

F

215.19

220.23

5.04

226.79

11.6

0

Rm8911

F

213.88

219.78

5.9

221.24

7.36

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

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

 

13 April 2018

and

11.35 to 11.36 AM

Rm8908

F

217.14

0.21

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

Group & Dose

(mg/kg

body weight)

Animal

Number

S

e

x

Observation

Necropsy

findings

Days

6

7

8

9

10

11

12

13

14

15

G2 and

1000

DRF

 

Rm8908

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

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

17 April 2018

and

9.53 AM

Rm8909

F

220.12

0.44

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

Group & Dose

(mg/kg

body weight)

Animal

Number

S

e

x

Observation

Necropsy

findings

Days

6

7

8

9

10

11

12

13

14

15

G3 and

2000

DRF

Rm8909

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

 

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 @

G3 and

2000

Main study

 

19 April 2018

and

10.38 to 10.39 AM

Rm8910

F

215.19

0.43

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

Rm8911

F

213.88

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)

Animal

Number

S

e

x

Observations

Necropsy

findings

Days

6

7

8

9

10

11

12

13

14

15

G3 and

2000

Main study

 

Rm8910

F

N

N

N

N

N

N

N

N

N

N

NAD

Rm8911

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 classified
Conclusions:
Based on the present study results, the acute dermal LD50 of 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1) is >2000 mg/kg body weight in female Wistar rats. The test item is classified as "Not classified”.
Executive summary:

The acute dermal toxicity of 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1) 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) 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. 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. Thus, it was concluded that the acute dermal median lethal dose (LD50) of 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1), when administered to female Wistar rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1) does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.