Ethyl 3,5,5-trimethylhexanoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male Wistar rats were exposed to 1 percent of the test item in 40 percent alcohol for 1 h (whole body exposure).

GLP compliance:

no

Remarks:

study performed before implementation of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 3,5,5-trimethylhexanoate

EC Number:

266-959-4

EC Name:

Ethyl 3,5,5-trimethylhexanoate

Cas Number:

67707-75-9

Molecular formula:

C11H22O2

IUPAC Name:

ethyl 3,5,5-trimethylhexanoate

Details on test material:

- Name of test material (as cited in study report): 3,5,5-Trimethyl-ethyl-capronat
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann GmbH, D-Borchen
- Age at study initiation: young adult
- Weight at study initiation: 130 – 150 g
- Fasting period before study: no (only during inhalation exposure period)
- Housing: in type 3 makrolon cages
- Diet (e.g. ad libitum): Altromin maintainance diet, 1324, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 22
- Humidity (%): approx. 50
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: 40% ethanol

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation exsiccator
- Exposure chamber volume: no data
- Source and rate of air: 200 L/h
- System of generating particulates/aerosols: nebuliser

TEST ATMOSPHERE
- Brief description of analytical method used: no data

VEHICLE
- Composition of vehicle (if applicable): 40% EtOH
- Concentration of test material in vehicle (if applicable): 1%
- Justification of choice of vehicle: relatively intoxic to rat

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

1 h

Concentrations:

1% in vehicle, corresponding to 1000 mg/m³ air

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology of upper trachea, mid trachea, lung (3 test animals + 3 control animals)

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 1 000 mg/m³ air (nominal)

Based on:

act. ingr.

Exp. duration:

1 h

Remarks on result:

other: no mortality

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 250 mg/m³ air (nominal)

Based on:

act. ingr.

Exp. duration:

4 h

Remarks on result:

other: extrapolated from 1 h value

Mortality:

no animals died

Clinical signs:

other: no clinical signs apart from temporarily impaired general condition directly after inhalation exposure

Body weight:

no data

Gross pathology:

Pathologically and histologically no compound specific alterations of the target organs (respiratory tract) could be observed.

Other findings:

Slight to moderate tracheitis was observed in all examined animals (test and control group). The lungs of all examined animals showed moderate to marked focal interstitial pneumonia, often combined with bronchitis and/or bronchopneumonia. In trachea and lung no qualitative or quantitative difference was observed between control and test group animals. Thus, the test substance did not show any specific substance related effects to the respiratory tract.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The 1 h LC0 of 3,5,5-Trimethyl-ethyl capronate in male rats was 1000 mg/m³ air.

Executive summary:

In an acute inhalation toxicity screening study, groups of 5 male young adult Wistar rats were exposed by inhalation route to 3,5,5-Trimethyl-ethyl capronate in 40% Ethanol for 1 hour to whole body at concentrations of 0 and 1%.  Animals then were observed for 7 days.

No animals died at the limit concentration of 1% in 40% Ethanol. No clinical signs apart from temporarily impaired general condition directly after inhalation exposure were observed.

Slight to moderate tracheitis was observed in all examined animals (test and control group). The lungs of all examined animals showed moderate to marked focal interstitial pneumonia, often combined with bronchitis and/or bronchopneumonia. In trachea and lung no qualitative or quantitative difference was observed between control and test group animals. Thus, the test substance did not show any specific substance related effects to the respiratory tract.

The 1 h LC0 was >= 1% test substance in 40% Ethanol, corresponding to 1000 mg/m³.

 “The ranges of the acute toxicity estimates (ATE) for inhalation toxicity [according to Regulation (EC) No 1272/2008] are based on 4-hour testing exposures. Conversion of existing inhalation toxicity data which have been generated using a 1-hour exposure can be carried out by dividing by a factor of […] 4 for dusts and mists.”

Based on this, a factor of 4 was used to extrapolate from 1 h exposure to 4 h exposure, resulting in a 4 h LC0 Males >=  0.25 mg/L air.