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Administrative data

Description of key information

Ethyl-S-lactate is practically non-toxic by the oral and inhalation route, but is irritating to the airway due to lactic acid formation at hydrolysis during uptake in the body.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 28, 1989 - October 12, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Breeding Centre for Laboratory Animals Çharles River Wiga GmbH", Sulzfeld, F.R. Germany.
- Age at study initiation: 5 weeks.
- Weight at study initiation: males: 139-158 g; females: 126-141 g.
- Fasting period before study: overnight.
- Housing: Groups of five animales, males and females separated in stainless cages eith wire-screen bottom and front.
- Diet (e.g. ad libitum): The Institute's cereal-based, open-formula basal diet for rats was fed to the animals ad libitum during the quarantine and study periods except for fasting prior to dosing.
- Water (e.g. ad libitum): Tap water was freely available at all times by means of an automatic watering system.
- Acclimation period: The rats were kept under the environmental conditions of the Institute's animal house for an acclimatization period of about 1 week prior to the test.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C.
- Humidity (%): 30-70%.
- Air changes (per hr): about 10 airchanges per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark.



IN-LIFE DATES: From: September 28, 1989 To:October 12, 1989
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was diluted with water in a concentration of 20% (w/v). The test dilution was given by gavage, in one single dose of 10 ml/kg body weight to five male and five female rats.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
A preliminary study was carried out to find the general level of acute toxicity for the test substance.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed frequently for signs of intoxication during the first 4 post-treatment hours and later on, at least once daily, throughout an observation period of 14 days. Individual body weights were recorded on day 0, 3, 7 and 14.
- Necropsy of survivors performed: At the end of the observation period, the rats were killed with carbon dioxide for macroscopic examination.
Statistics:
Since no mortality occurred a LD50 could not be calculated; a LD50 exceeding 2000 mg/kg body weight was given as a result.
Preliminary study:
A prelimary study was carried out to find the general level of acute toxicity of the test substance; data of this preliminary study were not presented in the report.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occcurred
Clinical signs:
At 1, 4 and 24 hours after treatment all animals showed moderate signs of piloerection. These signs of intoxication were not observed 48 hours after treatment and thereafter.

Body weight:
All animals gained weight after 3 days and thereafter, and no mortality occurred.
Gross pathology:
Macroscopic examination at the end of the observation period did not reveal any treatment-related gross alteration.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of ethyl-S-lactate is clearly less than the limit for classification as harmful
Executive summary:

Ethyl-S-lactate was administered to rats by oral gavage. The LD50 is higher than the upper limit for classification (2000 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The LD50 is higher than 2000 mg/kg bw.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
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
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
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.
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.

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

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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
5 400 mg/m³
Quality of whole database:
The substance is not acutely toxic in terms of systemic toxicity; however, there was a decrease in breathing frequency together with the wet nares and lachrymation, indicating respiratory irritation properties of the test material.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Ethyl-S-lactate was tested at limit concentrations and appeared practically non-toxic by the oral and inhalation route.

Oral administration of doses of 2000 mg/kg bw induced no mortality, and no clear signs of toxicity were seen in the surviving animals. At 5400 mg/m3 ethyl-S-lactate in air induced no mortality. 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 the exposure. These signs had all disappeared by the next day.

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

In a sensory irritation study, the RD50 values of ethyl-(L)-lactate were 772 mg/m³ in mice and 791 mg/m³ in rats. In the same study an RD50 of 760 mg/m³ in mice and 701 mg/m³ in rats was found for n-butyl-L-lactate. The similarity in the results for ethyl-L-lactate and n-butyl-L-lactate support the conclusion that the effects on breathing rate can be attributed to irritating effects from the lactic acid formed at hydrolysis of the substances (see statement in section 7.9.3), which is a rapid process during and after uptake in the organism. The sensory irritating effect is thus a pH effect and not a toxic effect.

Justification for classification or non-classification

Ethyl-S-lactate is practically non-toxic by the oral and inhalation route, but is irritating to the airway due to lactic acid formation at hydrolysis during uptake in the body.