1-phenylethanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 experimental 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

The objective of this acute oral toxicity study was to assess the toxicological profile of the test item when administered to rats by a single oral gavage.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

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-phenylethan-1-ol

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)

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.

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: 187.72 to 219.59 g
- Identification:By rat accession number. Identification of individual rats was by cage card and turmeric colour body markings. The rat accession number was allotted during the course of the study. The temporary body marking during acclimatization period was done with crystal violet.
- Fasting period before study: rats were fasted for approximately 16 to 18 hours
- Housing:Rats were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill
- 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, Mumbai, ad libitum
- Acclimation period: The animals were acclimatized six days for G1-FTS, eight days for G1-STS and twelve days for G2-FTS before treatment.

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: 27 April 2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 & 2000 mg/kg body weight.
- Amount of vehicle (if gavage):dose volume was 0.30 & 1.99 mL/kg body weight

Doses:

G1 (FTS) - 300 mg/kg
G1 (STS) - 300 mg/kg
G2 (FTS) - 2000 mg/kg

No. of animals per sex per dose:

G1 (FTS) - 300 mg/kg - 3
G1 (STS) - 300 mg/kg - 3
G2 (FTS) - 2000 mg/kg - 3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and pre-terminal deaths - At each step, the animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration. Observations included 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 the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded. Body weights - The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).
- Necropsy of survivors performed: yes, the rats surviving to the end of the observation period were euthanised by using isoflurane anaesthesia and subjected to detailed necropsy.
- Other examinations performed: Gross pathological findings were recorded and reported. 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

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no other details available

Mortality:

G1 (FTS) - 300 mg/kg - There were no pre-terminal deaths observed.
G1 (STS) - 300 mg/kg - There were no pre-terminal deaths observed.
G2 (FTS) - 2000 mg/kg - All the rats died at 1 hour post-dose.

Clinical signs:

other: G1 (FTS) - 300 mg/kg - Clinical signs of recumbency and ataxia – slight were observed in one rat at 30 minutes to 3 hours and the rat was normal from 4th hour onwards. G1 (STS) - 300 mg/kg - Clinical sign of ataxia – slight was observed in one rat at 30 m

Gross pathology:

There were no gross pathological changes at necropsy.

Other findings:

not specified

Any other information on results incl. tables

TABLE 1.      Body weight, body weight change and pre-terminal deaths

Group and Dose (mg/kg body weight)	Rat No.	Sex	Body weight (g)						Day of Death (Time of Death)	No. dead/ No. tested	Pre-terminal deaths (%)
			Initial (Day 1)	8^thday	Weight change (day 8 – Initial)	15^thday	Weight change (day 15 – Initial)	At Death
G1 (FTS) 300	Rm8895	F	209.41	225.63	16.22	238.18	28.77	-	-	0/3	0
	Rm8896	F	187.72	197.16	9.44	206.08	18.36	-	-
	Rm8897	F	209.99	226.15	16.16	232.04	22.05	-	-
G1 (STS) 300	Rm8898	F	209.31	215.81	6.5	227.11	17.80	-	-	0/3	0
	Rm8899	F	214.86	220.91	6.05	228.06	13.20	-	-
	Rm8900	F	193.13	201.97	8.84	211.97	18.84	-	-

G2 (FTS) 2000	Rm8901	F	196.12	-	-	-	-	196.57	1 (10.48 AM)	3/3	100
	Rm8902	F	219.59	-	-	-	-	219.97	1 (10.48 AM)
	Rm8903	F	214.48	-	-	-	-	214.64	1 (10.48 AM)

F: Female        FTS: First Treatment Step            STS: Second Treatment Step             NA: Not Applicable           

 

APPENDIX 1.      Individual clinical signs, dose administration and necropsy findings

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G1 (FTS) 300	11 April 2018 and 10:51 AM to 10:52 AM	Rm8895	F	209.41	0.06	N	N	N	N	N
		Rm8896	F	187.72	0.06	055 (b)	055 (b)	043 (1)	043 (1)	N
		Rm8897	F	209.99	0.06	N	N	N	N	N

Group and Dose (mg/kg body weight)

Rat No.

Sex

Day of observation

Necropsy Findings

2

3

4

5

6

7

8

9

10

11

12

13

14

15

G1 (FTS) 300

Rm8895

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8896

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8897

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

F: Female            FTS: First treatment step              N: Normal            min: minutes         mg: milligrams            kg: kilograms       

mL: millilitre         055 (b): Recumbent;            043 (1): Ataxia – slight;              NAD: No Abnormality Detected 

 

APPENDIX 2 contd. Individual clinical signs, dose administration and necropsy findings                 

 

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G1 (STS) 300	13 April 2018 and 11:30 AM to 11:33 AM	Rm8898	F	209.31	0.06	N	N	N	N	N
		Rm8899	F	214.86	0.06	N	N	N	N	N
		Rm8900	F	193.13	0.06	043 (1)	043 (1)	043 (1)	043 (1)	N

Group and Dose (mg/kg body weight)

Rat No.

Sex

Day of observation

Necropsy Findings

2

3

4

5

6

7

8

9

10

11

12

13

14

15

G1 (STS) 300

Rm8898

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8899

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8900

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

F: Female        STS: Second treatment step               N: Normal              min: minutes       mg: milligrams                      kg: kilograms             

mL: millilitre         043 (1): Ataxia – slight;             NAD: No Abnormality Detected           

 

APPENDIX 2 contd. Individual clinical signs, dose administration and necropsy findings                 

 

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G2 (FTS) 2000	17 April 2018 and 9:47 AM to 9:49 AM	Rm8901	F	196.12	0.39	055 (b)	016	-	-	-
		Rm8902	F	219.59	0.44	055 (b)	016	-	-	-
		Rm8903	F	214.48	0.43	055 (b)	016	-	-	-

Group and Dose (mg/kg body weight)	Rat No.	Sex	Day of observation														Necropsy Findings
			2	3	4	5	6	7	8	9	10	11	12	13	14	15
G2 (FTS) 2000	Rm8901	F	-	-	-	-	-	-	-	-	-	-	-	-	-	-	NAD
	Rm8902	F	-	-	-	-	-	-	-	-	-	-	-	-	-	-	NAD
	Rm8903	F	-	-	-	-	-	-	-	-	-	-	-	-	-	-	NAD

F: Female         FTS: First treatment step                 min: minutes   mg: milligrams                       kg: kilograms     mL: millilitre      

055 (b): Recumbent;    016: Dead;              NAD: No Abnormality Detected

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of the present study, The LD50 of 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1) is 500 mg/kg as per the as per LD50 cut-off value. The test item is classified as “Category 4 (300 – ≤ 2000)” criteria of CLP.

Executive summary:

The acute oral toxicity study of 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1) in Wistar rats was conducted to assess the toxicological profile of the test item. Undiluted test item (Purity: 99.8%) was administered via oral gavage route. The dose volume was 0.30 mL/kg to attain the dose of 300 mg/kg body weight. A single oral gavage administration was done to overnight fasted (approximately 16 to 18 hours) three female rats (G1-FTS) at the dose of 300 mg/kg body weight. Clinical signs of recumbency and ataxia - slight were observed in one rat at 30 minutes to 3 hours and the rat was normal from 4th hour onwards and no pre-terminal deaths were observed, hence three additional female rats were tested at the same dose of 300 mg/kg body weight (G1-STS). The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. Clinical signs of ataxia - slight were observed in one rat at 30 minutes to 3 hours and the rat was normal from 4th hour onwards and no pre-terminal deaths were observed. All survived rats gained weight during experimental period. There were no gross pathological changes at necropsy. The treatment was continued with the next higher dose of 2000 mg/kg body weight (1.99 mL/kg body weight) - G2-FTS. The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. Clinical sign of recumbency was observed in all the three rats and all the rats died at 1 hour post-dose, the dosing was stopped. Thus, the acute oral LD50 (Cut-off value) of 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1) was considered to be 500 mg/kg body weight. Thus, it was concluded that the acute toxicity study of 1-phenylethan-1-ol (1-phenylethanol) (CAS No. 98-85-1), when administered via oral route in Wistar rats falls into the “Category 4 (300 – ≤ 2000)” criteria of CLP.