Ethyl butyrate

Skin irritation / corrosion

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 following standard procedures

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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 determine the dermal reaction profile of the test chemical in Sprague Dawley rats

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl butyrate

EC Number:

203-306-4

EC Name:

Ethyl butyrate

Cas Number:

105-54-4

Molecular formula:

C6H12O2

IUPAC Name:

ethyl butanoate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: Male and Female
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks
- Weight at study initiation: Body weights at the start : Male - Mean: 258.62 g (= 100 %); Minimum : 251.4 g (- 2.79 %); Maximum : 266.4 g (+ 3.01 %)
Total No. of animals : 5
Female- Mean : 230.04 g (= 100 %); Minimum : 224.3 g (- 2.50 %); Maximum : 238.4 g (+ 3.63 %)
Total No. of animals : 5
- Housing:individually housed in polycarbonate cages with paddy husk as bedding
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum):Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period:All animals were acclimatized to laboratory conditions for minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 to 22.0 degree centigrade
- Humidity (%): 55.4% to 58.8%.
- Air changes (per hr): ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

2000 mg/kg

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

10(5/sex)

Details on study design:

TEST SITE
- Area of exposure: Dorsal surface and sides from scapular to pelvic area.
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.
- Time after start of exposure: 24 hours
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : Observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours
on the day of dosing and once daily thereafter for 14 day.
SCORING SYSTEM: Draize Method.
Grading of Skin Reaction
1. Erythema and Eschar Formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight
Eschar formation (injuries in depth) 4
Maximum possible = 4

2. Oedema Formation
No oedema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm 3
Severe edema (raised more than 1 mm and extending
Beyond area of exposure) 4
Maximum possible = 4

3. Other dermal abnormalities (not indicative of irritation)
Desquamation………………………………………………………..D
Exfoliation (of eschar)……………………………………………….Ex

Draize, J. H.: Appraisal of the safety of chemicals in foods, drugs and cosmetics: pp 46-49 Assoc. of food and drug officials of the united states, Topka, Kansas (1965).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

14 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

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:

Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Other effects:

Clinical Signs of Toxicity and Mortality
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
Gross Pathological Findings
Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.

Any other information on results incl. tables

Summary of Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/025

Test System : Sprague Dawley Rat

Sex : Male 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No dermal reaction observed	5	1 - 5	Day 0 - Day 14	0/5

 

Sex : Female

 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No dermal reaction observed	5	6 - 10	Day 0 - Day 14	0/5

 

Individual Animal - Evaluation of Dermal Reactions

Laboratory Test Item Code :TAS/122/025

Test System : Sprague Dawley Rat

Sex : Male  

Group : I

Dose  : 2000 mg/kg body weight

Animal	Dermal	D A Y S
No.	Reaction	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
1	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
4	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

Sex : Female  

Group : I

Dose  : 2000 mg/kg body weight

Animal	Dermal	D A Y S
No.	Reaction	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
6	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
7	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
8	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
9	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
10	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

 

Summary of Clinical Signs of Toxicity and Mortality

 

Laboratory Test Item Code :TAS/122/025

Test System : Sprague Dawley Rat

Sex : Male

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	5	1 - 5	Day 0 - Day 14	0/5

 

 

Sex : Female

 

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	5	6 - 10	Day 0 - Day 14	0/5

Mean Body Weight and Percent Body Weight Gain (g)

 

Laboratory Test Item Code :TAS/122/025

Test System : Sprague Dawley Rat

Sex : Male

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	258.62	283.10	9.46	303.84	7.33	17.48
		± SD	5.70	6.54	0.57	7.88	1.51	1.35

 

 Sex : Female

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	230.04	241.18	4.84	252.74	4.79	9.86
		± SD	5.50	6.35	0.50	7.32	0.44	0.83

Summary of Gross Pathological Findings

Laboratory Test Item Code :TAS/122/025

Test System : Sprague Dawley Rat

 

Sex : Male

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	1 - 5	TS	No abnormality detected

Sex : Female

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	6 - 10	TS	No abnormality detected

                     TS = Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal. Hence, it was concluded that the test chemical was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance,the test chemical can be classified under the category "Not Classified" as per CLP regulation.

Executive summary:

A study was designed and conducted to determine the acute dermal toxicity profile of the test chemical in Sprague Dawley rats. 10(5/sex) young adult Sprague Dawley rats were used for the study.

The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period.

 

Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item.Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.   

Animals exhibited normal body weight gain through the study period of 14 days.Gross pathological examination did not reveal any abnormalities attributable to the treatment.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal.  Hence, it was concluded that the test chemical was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance,the test chemical can be classified under the category "Not Classified" as per CLP regulation.