Isopropyl 2-methylbutyrate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 May and 11 May 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target chemicals are analagous

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source and target chemicals are both pure with low impurity.

3. ANALOGUE APPROACH JUSTIFICATION
In light of the structural and physico-chemical similarities between EMB, EMV and IMB it is our consideration that experimental testing for an acute dermal repeated dose toxicity study using IMB can be waived, as study data from the structurally related esters EMB and EMV can be used to read-across and predict the toxicity of IMB.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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 (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 2-methylbutyrate

EC Number:

231-225-4

EC Name:

Ethyl 2-methylbutyrate

Cas Number:

7452-79-1

Molecular formula:

C7H14O2

IUPAC Name:

Butanoic acid, 2-methyl-, ethyl ester

Constituent 2

Reference substance name:

Ethyl Methylbutyrate-2

IUPAC Name:

Ethyl Methylbutyrate-2

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Ethyl Methylbutyrate-2
- Molecular formula (if other than submission substance): C7H14O2
- Molecular weight (if other than submission substance): 130.21 g/mol
- Physical state: Colourless liquid
- Analytical purity: 99.4%
- Lot/batch No.: 20010036
- Storage condition of test material: Approximately 4°C in the dark
- Other:
- Date received: 08 May 2000

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 20010036

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: approx. 4°C in the dark.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: approximately 8 to 12 weeks old
- Weight at study initiation: males weighed 222 to 231g, and the females 215 to 226g
- Fasting period before study: No details provided in report
- Housing: The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Acclimation period: minimum acclimatisation period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
(Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study).
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- The calculated volume of the test material, as received, was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.
- Time after start of exposure: After the 24-hour contact period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dose volume 2.33 ml/kg and Specific gravity 0.861 (Dose level 2000 mg/kg)

Duration of exposure:

24 hours

Doses:

Dose volume: 2.33 ml/kg
Specific gravity: 0.861
Dose level: 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
- Other examinations performed: After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) “Dermal and Eye Toxicity Tests” In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31 (see attached report for details). Any other skin reactions, if present were also recorded.

Statistics:

No details provided in report

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:

There were no deaths

Clinical signs:

No clinical signs of toxicity were noted during the study.

Body weight:

All animals showed expected gain in bodyweight during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No signs of dermal irritation were noted during the study.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

The acute dermal median lethal dose (LD50) of the test material, ETHYL METHYLBUTYRATE-2, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.