Isopropyl 2-methylbutyrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 April to 19 May 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The substance is an analogue of IMB

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target substances have similar purities and few impurities.

3. ANALOGUE APPROACH JUSTIFICATION
All three substances are Cramer class 1 (simple chemical structure with low order oral toxicity with a toxicological threshold of 1800µg/person/day or 30µg/kg bw/day) and have similar chemical and physico-chemical properties, being short chain aliphatic esters. Each is rapidly hydrolysed by esterases to form constituent alcohols and carboxylic acids which become substrates for β-oxidation. For each substance, toxicological endpoint classification is identical for acute oral toxicity, skin irritation and mutagenicity (point mutation, gene mutation and structural chromosomal aberrations).

In light of the structural and physico-chemical similarities between EMB, EMV and IMB it is our consideration that experimental testing for an acute inhalation 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:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed concentration procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 2-methylvalerate

EC Number:

254-384-1

EC Name:

Ethyl 2-methylvalerate

Cas Number:

39255-32-8

Molecular formula:

C8H16O2

IUPAC Name:

ethyl 2-methylpentanoate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Toyo Gosei / H3-G-26
- Expiration date of the lot/batch: 25 July 2014
- Purity test date: No data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In original container at 2° to 8°Cin the dark.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal breeding facility
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10-11 weeks
- Weight at study initiation: male 285 to 303g and female 199 to 204g
- Fasting period before study: no data
- Housing: polypropylene rat cages covered with stainless steel grid tops
- Diet: High Fiber feed ad libitum
- Water: UV sterilised ad libitum
- Acclimation period: 26 hours

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19° to 22°C
- Humidity (%): 64 to 65%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12:12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

not specified

Mass median aerodynamic diameter (MMAD):

ca. 1 - ca. 4 µm

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ht 30cm; 30cm internal diameter;
- Exposure chamber volume: 63.5 litres
- Method of holding animals in test chamber: single transparent perspex exposure tube.
- Source and rate of air: 15 changes per hour.
- Method of conditioning air: no data
- System of generating particulates/aerosols: spray atomiser
- Method of particle size determination: seven-stage cascade impactor
- Treatment of exhaust air: passes through 1.0% sodium hydroxide and moisture traps containing silica gel.
- Temperature, humidity, pressure in air chamber: 22.4 to 22.6°C; 43.7 to 44.4% RH. A slight negative pressure was maintained inside the chamber by keeping the air outflow rate slightly more than the air inflow rate, to prevent leakage of the test item into the surrounding area.

TEST ATMOSPHERE
- Brief description of analytical method used: open face sampler with glass microfibre papers
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): not applicable.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter): 1 to 4µm

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Remarks on duration:

In addition to the 4 hour exposure there was a 15 minute equilibration period.

Concentrations:

5.967 mg / l air

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 1, 3, 7 and 14.
- Necropsy of survivors performed: yeso
- Other examinations performed: clinical signs, body weight,organ weights, histopathology,

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.967 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

None

Clinical signs:

other: None

Body weight:

Mean body weight of rats post-exposure equalled or increased on days 1, 3, 7 and 14 in both sexes of rats when compared with pre-exposure (day 0) mean body weight.

Gross pathology:

Visceral examination did not reveal any lesions of pathological significance.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results of this study ethyl 2-methylvalerate was found to be non-toxic and will not be classified for inhaltion toxicity.