Ethyl isovalerate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-11-03 to 2017-02-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl propionate

EC Number:

203-291-4

EC Name:

Ethyl propionate

Cas Number:

105-37-3

Molecular formula:

C5H10O2

IUPAC Name:

ethyl propionate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Males 8 weeks old; Females 9 weeks old
- Weight at study initiation: Males 267.5-283.4g; Females 217.6-231.5g
- Housing: one animal per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: for four days after three days of quarantine (including health examinations)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1-24.6°C (measured), permissible range 19.0-25.0°C
- Humidity (%): 47.7-61-7% (measured), permissible range 30.0-70.0%
- Air changes (per hr): 10-15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surface
- % coverage:
- Type of wrap if used: lint, Soft Cloth Tape with Liner and surgical tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton moistened with tepid water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.25 mL/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose;

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality, clinical signs, general conditions at 30 minutes after dosing and at 1, 2, 4, 6 hours after dosing on day 0 and once daily thereafter for 14 days; body weight was recorded prior to dosing on day 0 and on day 1, 3, 7, and on day of necropsy, day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no histopathology, since no gross findings were observed at necropsy.

Statistics:

Statistical analysis was performed using SAS progam V9.3.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals at 2000 mg/kg bw and in the control group survived the duration of the study. There were no effects on the mortality. (see table 1)

Clinical signs:

other: All animals at 2000 mg/kg bw and in the control group showed no abnormalities of clinical signs. (see table 2)

Gross pathology:

No grossly visible evidence of morphological abnormalities were observed in any animal at 2000 mg/kg bw or in the control group.

Any other information on results incl. tables

Table 1: Summary of Mortality

Sex	dose (mg/kg)	No. animals	Days after dosing															mortality
			0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
male	0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/5
	2000	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/5
Female	0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/5
	2000	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/5

Table 2: Individual Clinical Signs

Sex	Dose (mg/kg)	No. animals	Clinical sign	Hours (day 0) after dosing
				0.5	1	2	4	6
Male	0	5	NOA	5	5	5	5	5
	2000	5	NOA	5	5	5	5	5
Female	0	5	NOA	5	5	5	5	5
	2000	5	NOA	5	5	5	5	5

Sex	Dose (mg/kg)	No. animals	Clinical sign	Days after
				1	2	3	4	5	6	7	8	9	10	11	12	13	14
Male	0	5	NOA	5	5	5	5	5	5	5	5	5	5	5	5	5	5
	2000	5	NOA	5	5	5	5	5	5	5	5	5	5	5	5	5	5
Female	0	5	NOA	5	5	5	5	5	5	5	5	5	5	5	5	5	5
	2000	5	NOA	5	5	5	5	5	5	5	5	5	5	5	5	5	5

NOA: No observable abnormality

Table 3: Individual Body Weights

Sex	Dose		Days after dosing				Gain
			0	3	7	14	0-14
Male	0	Mean	274.9	288.3	315.7	358.1	83.2
		S.D.	3.2	1.9	6.9	12.8	12.4
		N	5	5	5	5	5
	2000	Mean	276.0	284.1	305.2	344.9	68.9
		S.D.	6.8	10.2	12.1	18.9	14.1
		N	5	5	5	5	5
Female	0	Mean	225.5	228.0	237.2	248.4	22.9
		S.D.	4.9	3.2	7.5	14.0	10.0
		N	5	5	5	5	5
	2000	Mean	226.3	227.6	239.2	254.4	28.2
		S.D.	7.0	2.4	4.4	5.2	8.7
		N	5	5	5	5	5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of the acute dermal study in Sprague-dawley rats, the test substance has an LD50 value greater than 2000 mg/kg bw.

Executive summary:

The purpose of this study was to assess the potential toxicity and the approximate LD50 value of the test substance following a single dermal application to Sprague-Dawley rats.

 

Test groups consisted of one dose group at a dose of 2,000 mg/kg and a control group, and each group consisted of 5 males and 5 females. All animals were monitored for clinical signs and body weight changes after dosing during the 14-day observation period. They were subjected to gross necropsy at the end of the observation period.

 

There were no deaths of animals in the 2,000 mg/kg groups. No test substance-related effects were observed in clinical signs, body weight data or necropsy findings in the 2,000 mg/kg groups.

 

Based on the result of this study, the LD50 value of the test substance was considered to be greater than 2,000 mg/kg in male and female rats under the conditions of this study. Therefore, it was not classified according to CLP.