2-ethylhexan-1-ol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-03-30 through 1989-04-12

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Acceptable, well-documented study report which meets basic scientific principles. Original report available as copy. Restriction: low number of animals, short observation period. Only 2 dose levels tested. Restriction acceptable because of low test substance volatility. No data on gross pathology.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

only 2 dose levels; low animal numbers; 7 day observation period

Principles of method if other than guideline:

Method: similar to OECD 403 with restrictions: 2 dose levels tested. 3 animals per sex and dose level were tested. Test atmosphere concentration and particle size was determined. Observation period was 7 days.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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): C-1257
- Physical state: clear liquid
- Analytical purity: 99.5%
- Storage condition of test material: cool ventilated cabinets or fume hoods

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 Breeding Laboratories, Inc., Raleigh, North Carolina
- Age at study initiation: Group I Group II
Males 8 weeks 9 weeks
Males 9 weeks 11 weeks

- Weight at study initiation: Group I Group II
Males: range: 230-238 g; 350-335 g
mean: 235g 353g
Females: range: 221-228 g; 250-265 g
mean: 225g 258g



- Fasting period before study:
- Housing: in stainless steel wire mesh cages; in groups of 2 during the first week of acclimatisation; singly thereafter
- Diet (e.g. ad libitum): standard laboratory diet (Purina Rodent laboratory Chow Brand Animal Diet #5001)
- Water (e.g. ad libitum): automated watering system
- Acclimation period: 1 week (Group I) and 3 weeks (Group II)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 67-76°F
- Humidity (%): 40-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12hrs dark/12 hrs light

Administration / exposure

Route of administration:

other: Group I: vapour + aerosol; Group II: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexigla / glass exposure chamber
- Exposure chamber volume: 100 L
- Method of holding animals in test chamber: animals were caged
- Source and rate of air: house-supply air
- System of generating particulates/aerosols:
Group I: the test material was placed into a 250 mL Erlenmeyer flask from where it was delivered by a fluid metering pump into the fluid inlet of an air atomizing nozzle. House-supply air was delivered through the air inlet to the atomizer to generate the aerosol which was directed into the exposure chamber.
Group II: air was drawn through 2 glass bubblers, place in water bath in tandem, which contained the test material. The air was heated to 50°C in the first and 30°C in the second bubbler; the air was then directed to a 3-neck flask containing glass wool before the filtered air was directed to the exposure chamber.

- Method of particle size determination:
Group I: once during exposure using a Delron DCI-6 Cascade Impactor.
Group II: hourly during exposure using a TSI Aerodynamic Particle Sizer (Model 3300)



TEST ATMOSPHERE
- Brief description of analytical method used:
Group I: gravimetric determination of test material drawn from the breathing zone onto glass microfibre filter paper followed by a charcoal tube. The gravimetric concentration (aerosol/vapour/total) was calculated by dividing the weight difference in mg by the volume of air sampled in L.

Group II: hourly samples were drawn and directed to a IRAN 1A Ambient Air Analyzer. The exposure level was determined from the absorbance using a calibration curve constructed using the same equipment.

- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable): none


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Group I: 81% of particles < 10 microns
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Group I: 5.6 microns (geometric st. dev. 1.9)
Group II: no aerosol formation was considered, due to very low levels of particulates (0.015 mg/m³)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.89 mg/L (vapour) and 5.3 mg/L (mixed vapour and aerosol)

No. of animals per sex per dose:

3

Control animals:

other: historical controls

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: viability was assessed twice daily. Body weights were determined on days 1 (immediately prior to exposure) and on day 8 (prior to sacrifice).
- Necropsy of survivors performed: no

Statistics:

none

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.89 - <= 5.3 mg/L air

Exp. duration:

4 h

Remarks on result:

other: 0.89 mg/L (vapour); 5.3 mg/L (mixed vapour (1.1 mg/L) and aerosol (4.3 mg/L))

Mortality:

Group I: all animals died (6/6)
Group II: no animals died (0/6)

Clinical signs:

other: Group I: 4 animals died during the exposure period or shortly thereafter. Observations included laboured breathing, nasal discharge, prostration, and closed eyes.

Body weight:

Group I: 4 animals died during the exposure period or shortly thereafter.
Group II: decreased activity was noted during exposure; after the exposure the animals were unremarkable, and most gained weight during the following week.

Gross pathology:

No data

Any other information on results incl. tables

The proportion of inspirable aerosol was high in the first experiment with Group I, and there was a large discrepancy between the measured and the nominal concentration which was calculated from the amount of test material consumed during the exposure.

In experiment I the measured concentration was only 12.3% compared to the nominal concentration which was calculated from the consumed test material.

The differences in nominal and measured exposure concentrations are attributed to impaction or sedimentation or absorption of the aerosol/vapour on the surfaces in the exposure chamber.

Group	Concentration (mg/L)
	aerosol	vapour	total	nominal
I	4.3	1.1	5.3	43
II	-	0.89	0.89	2.5

Within the study report the vapour saturation concentration was calculated to be 1.4 mg/L at 20°C, based on the vapour pressure of 0.2 mm Hg (i.e. 0.267 hPa).

When using the vapour pressure of 0.93 hPa, which was obtained in a highly reliable and newly available study, a saturated vapour concentration of 4.9 mg/L (i.e. 4884 mg/cubicmetre) can be calculated.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the The LC50 was >0.89 mg/L. The complete mortality in the first experiment was attributed to the high proportion of respirable aerosol.

Executive summary:

Following the 4 hour inhalation exposure to 0.89 mg 2-EH/L no mortalities or clinical signs of toxicity were noted in male and female Sprague-Dawley rats within the 7-day observation period.

In contrast, all animals of the 5 mg/L target concentration group died, 4 of them during the exposure or shortly thereafter. It was, however, demonstrated that only 20% of the measured concentration was attributable to vapour whereas 80% was represented by particulates. The majority of the particulates (81%) had a mean aerodynamic diameter of 10 µm and were thus respirable by rats. The measured concentration was only 12.3% compared to the nominal concentration which was calculated from the consumed test material.

Based on the above it is concluded that the 4-hour LC50 in rats was >0.89 mg/L (BioDynamics, 1989).