Fatty acids, C16-18, 2-ethylhexyl esters

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

Oktober 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: no particle size determination; lack of details on test substance; no rationale given for chosen test concentration (targeted conc. was 2 mg/L)

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexan-1-ol

EC Number:

203-234-3

EC Name:

2-ethylhexan-1-ol

Cas Number:

104-76-7

Molecular formula:

C8H18O

IUPAC Name:

2-ethylhexan-1-ol

Details on test material:

- Name of test material (as cited in study report): 2-Ethyl hexanol
- Physical state: colorless liquid
- Purity: technical grade
- Stability: stable at room temperature
- Expiration date: 31 December 1989
- Test article preparation: the test article was used as supplied by the Sponsor and generated by nebulization.

Test animals

Species:

rat

Strain:

other: Wistar rat, KFM-Han (outbred), SPF quality.

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Fuellinsdorf, Switzerland
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 180-199.4 g for males; 180-199.6 g for females;
- Fasting period before study: no data
- Housing: groups of five in Makrolon type 4 cages with standard softwood bedding
- Diet (e.g. ad libitum): standard pellet diet, Kliba 343, Batch 42/89 and 45/89
- Water (e.g. ad libitum): tap water from Geneva, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Inhalation was performed according to the method of Sachsse et al., 1973: "Measurements of Inhalation Toxicity of Aerosols in Small Laboratory Animals".
- Exposure apparatus:
The animals are confined separately in tubes which are positioned radially around the exposure chamber. The flow-past, nose-only design of this exposure system has been developed based upon the fluid dynamic modeling of the aerosol flow from the entry to the animal‘s nose. The internal active volume of the chamber tor exposing 40 animals by nose only is one liter. The resulting time for the concentration at an animal port to reach 99 % of its ultimate value (T99) is 34 seconds for the 40 animal chambers.
This system is constructed of anodised aluminium and readily accepts a variety of different sized Makrolon animal restraint tubes which have been designed in consideration of the anatomy and physiology of the rodent. The test article stream reaches the animal‘s nose through ports situated at different levels around the axis of the exposure chamber. Each level has 8 ports and can be rotated, allowing dose observation of all the animals without interruption of exposure. The entire unit is modular, permitting easy cleaning and the choice of how many levels of animals will be used.
The system is unique in comparison with conventional nose-only exposure systems in that it insures a uniform distribution of the test article at all chamber levels, provides a constant stream of "fresh" test article to each animal, and precludes rebreathing of the exhaled air.

- Exposure chamber volume: 1 L
- Method of holding animals in test chamber: restraint tubes
- Source and rate of air: no further details given
- Method of conditioning air: no further details given
- System of generating particulates/aerosols: The test article was placed in an automatic syringe pump feeding a nebulizer (No. 950, Hospitak, New York, U.S.A.). The test atmosphere generated by the nebulizer was then diluted with clean air to achieve the concentration required for this study and discharged into the exposure chamber.
- Method of particle size determination: not determined
- Temperature, humidity: temperature: 21 ºC; relative humidity: 0.6 %; oxygen concentration: 20.9 vol%;

TEST ATMOSPHERE
- Brief description of analytical method used: The test article concentration, oxygen concentration, relative humidity and temperature were measured on test atmosphere samples taken at the site of the animal's snout in the exposure system. Analytical determinations were performed by GC.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not determined
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not determined

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Aerosol samples were prepared by passing through three bottles, each filled with acetone and cooled to with dry ice and analyzed by GC.

Duration of exposure:

4 h

Concentrations:

1.49 mg/L
(The target concentration was 2 mg/L air)

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days
Clinical signs and mortality were observed once per hour during exposure, once after exposure on the day of testing and twice daily thereafter.
Body weights were recorded prior to exposure and weekly thereafter.
All animals were necropsied and subjected to gross macroscopic examination.
Lungs, trachea and larynx were collected and fixed from all animals.

Statistics:

none

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.49 mg/L air

Based on:

test mat.

Remarks:

highest attainable liquid aerosol concentration

Exp. duration:

4 h

Mortality:

No deaths occured during exposure nor during the 15-day observation period.

Clinical signs:

other: No clinical signs were observed during or following exposure nor during the 15-day observation period.

Body weight:

No treatment-related effects on body weights were noted

Gross pathology:

No macroscopic changes were observed.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Assuming that the given concentration is the highest attainable liquid aerosol concentration, no classification is required.