Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
, the observation period lasted 15 days instead of 14 days
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: SPF-reared, Wistar derived rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Wiga, Sulzfeld, FRG.
- Age at study initiation: young adult.
- Weight at study initiation: 259 g (male) and 174 g (female).
- Housing: the rats were housed in groups of five animals, males and females separated. They were housed under conventional conditions in the anmimal room in suspended stainless steel cages fitted with wire-mesh floor and front.
- Diet (e.g. ad libitum): the Institute's stock diet for rats was provided at libitum.
- Water (e.g. ad libitum): water was provided from an automatic drinking-water system ad libitum.
- Acclimation period: the animals were acclimatized in a cleaned and disinfected animal room in the inhalation facilities until the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.6 - 23.9°C
- Humidity (%): 42-58%
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): 12-hour light and 12-hour dark cylce was maintained.


IN-LIFE DATES: From: December 11, 1989 To: December 26, 1989

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure chamber:
Animals were exposed tot the test atmosphere in an all glass, total body inhalation chamber of the Institute's design with a capacity of about 0.102 m³. The test atmosphere entered at the bottom of the chamber and exited through an exhaust pipe at the top. During exposure the animals were housed individually in cages constructed of stainless steel wire mesh. Ports in the wall of the inhalation chamber allowed sampling of the test atmosphere. The total air flow through the chamber was 1.05 m³ per hour, resulting in about 10 air changes per hour. Both the temperature and the relative humidity were measured at the outlet of the chamber two times per hour. The temperature was 21 ± 0°C. Relative humidity turned out to be 74.5 ± 1.4%.
Generation of test atmosphere:
The vapour pressure of ethyl lactate is relatively low for generating a test atmosphere at a vapour concentration of at least 5 g/m³. Therefore, the test atmosphere was generated by nebulizing ethyl lactate. It was expected that the major part of the aerosol particles would evaporate. For the generation of the aerosol ethyl lactate was metered by a roller pump to a Rhema air driven nebulizer. The aerosol was blown into a mixing chamber, to allow the aerosol particles to mix with air and to evaporate. Next, the resulting test atmosphere was passed to the inhalation chamber.

- Method of particle size determination: A particle size analysis was performed using an 11-stage cascade impactor to show the possible presence of aerosol in the test atmosphere

TEST ATMOSPHERE
The actual concentration of ethyl lactate in the test atmosphere was determined by gas chromatography. An Intersmat I 53 GC equiped with flame ionization detector was used. The response of the flame ionization detector (FID) to ethyl lactate was calibrated, by injecting 1 µl of a calibration solution ccontaining 100 mg ethyl lactate/25 ml demineralised water into the gaschromatograph. Forty liter samples of teh test atmosphere were bubbled through 35 ml of demineralised water. After sampling, the sample fluid was made up with demineralised water to a volume of 50 ml. The concentration of ethyl lactate in the sampling fluid was determined by injecting 1 µl of the sample fluid into the gas chromatograph. From the response of the FID to the sampling fluids, the volume of sampling fluid and the volume of test atmosphere passe through the bubbler the concentration could be calculated. The nominal concentration of ethyl lactate was determined by dividing the amount of test material used by the total volume of air drawn through the inhalation chamber.


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


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:
Analytical verification of test atmosphere concentrations:
yes
Remarks:
determined by gas chromatography
Duration of exposure:
4 h
Concentrations:
actual concentation of ethyl lactate in the test atmosphere turned out to be 5.4 ± 0.4 g/m³. The nominal concentration was 17.6 g/m³. From the determination of the particle size distribution it appeared that no aerosol could be shown. This does not necessarily mean that there were no droplets in the test atmosphere, since it is very likely that after deposition of the droplets in the impactor the ethy lactate has evaporated. Actually, the large difference between actual and nominal concentration points to loss of test material, which at this high concentration level only is observed during aerosol exposures.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
During the exposure the animals were deprived of food and water, and were housed individually/ Immediately after the exposure, the animals were returned tot their living cages (5 males or 5 females to a cage) and were held for an observation period of 15 days. The observation period was extended with one day because day 14 fell on Chirstmas day.
The rats were visually inspected for reactions to treatment after 15, 30, 60, 120 and 240 min. after the start of tehexposure, and once daily during teh observation period.
Body weights were recorded just prior to exposure and at days 7, 14 and 15. At teh end of the observation period, the rats were killed by exsanguination from the abdominal aorta under ether anaesthesia, autopsied and examined for gross pathological changes.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.4 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC0
Effect level:
5.4 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None of the rats died during or after exposure.
Clinical signs:
other: During the entire exposure the animals showed a decreased breathing frequency. Wet noses were seen after 30 minutes of exposure and piloerection after 60 minutes. Half closed eyes and lachrymation were all observed only at 15 minutes after the start of th
Body weight:
Body weight gain was not visibly affected by the exposure. All animals gained weight in a normal way.
Gross pathology:
Gross-examination at autopsy revealed pale lungs in one male and three females. In three females the lungs showed a few petechiae.

Any other information on results incl. tables

The decrease in breathing frequency together with the wet nares and lachrymation are indicative of irritational properties of the test material.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 4-hour LC50 of ethyl lactate in rats is higher than 5.4 g/L. The results are in line with findings in the oral study.
Executive summary:

Ethyl lactate was tested for its acute inhalation toxicity. Male and female SPF-reared, Wistar derived rats were exposed to a concentration of approximately 5.4 mg/L for 4 hours. A decreased breathing rate was observed during exposure. Wet noses were seen after 30 minuter of exposure and piloerection after 60 minutes. Half closed eyes and lachrymation were all observed only at 15 minutes after the start of the exposure. These signs had all disappeared the next day.All animals appearde normal for the remainder of the 15 day observation period and gained weight in a normal way. All animals survived till the end of the study. Gross-examination at autopsy revealed pale lungs in one male and three females. In three females the lungs showed a few petechiae. The level of 5.4 mg/L was the maxiumum attainable concentration due to the physical properties of the test material. Based on these results, the LC50 of ethyl lactate is greater than 5.4 mg/L