Ethyl (S)-2-hydroxypropionate

Endpoint summary

Description of key information

In an acute oral toxicity study conducted according to OECD guideline 401, groups of Wistar rats (5/sex) were given Ethyl (S)-lactate (99.5 % purity) as a single oral dose of 2000 mg/kg bw. No mortality occurred and an oral LD50 value of greater than 2000 mg/kg bw, both in male and female rats, was determined in this study.

In an acute inhalation study conducted according to OECD guideline 403, groups of Wistar rats (5/sex) were exposed to 5.4 mg/L Ethyl lactate for 4 hours. No mortality occurred and thus the LC50 can be considered to be greater than 5.4 mg/L.

In an acute inhalation toxicity study, young adult Wistar rats (5/sex), were exposed to aerosols of Ethyl lactate at a concentration of 5.4 mg/L in air for 4 hours. No mortality occurred and based on the result from this key study, the LC50 is considered to be greater than 5.14 mg/L.

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:

1989-09-28 to 1995-08-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material used in the report: ethyl lactate
- CAS number: 687-47-8 (confirmed by sponsor)
- Trade name: Purasolv EL
- Batch number: EA 0188F
- Appearance: liquid
- Purity: 99.5%
- Storage: at room temperature, in the dark

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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 animals, males and females separated in stainless cages either 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 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark.

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 bw

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 bw 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.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occcurred

Clinical signs:

other: 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.

Gross pathology:

Macroscopic examination at the end of the observation period did not reveal any treatment-related gross alteration.

Interpretation of results:

other: CLP criteria not met

Conclusions:

In an acute oral toxicity study in rats conducted according to OECD Test Guideline 401, no mortality occurred at the limit dose of 2000 mg/kg bw. Based on the results and in accordance with OECD Guideline 401, the oral LD50 was determined to be greater than 2000 mg/kg bw in both male and female rats.

Executive summary:

In an acute oral toxicity study conducted according to OECD Test Guideline 401, groups of Wistar rats (n= 5/sex) were given a single oral dose of Ethyl (S)-lactate (purity: 99.5%) in water at a dose of 2000 mg/kg bw and were observed for 14 days. All animals survived until the end of the study. 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. All animals gained weight after 3 days and thereafter. At necropsy, no treatment-related macroscopic findings were observed in any animal.

Based on the results the LD50 value was determined to be greater than 2000 mg/kg bw. Therefore, classification for acute oral toxicity according to the CLP Regulation 1272/2008 is not warranted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.4 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

None of the rats died during or after exposure.

Clinical signs:

other: See remarks

Remarks:

During the entire exposure dreased 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 study

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:

other: CLP criteria not met

Conclusions:

In an acute inhalation toxicity study in rats conducted according to OECD Test Guideline 403, no mortality occurred at the concentration of 5.4 mg/L air. Based on the results and in accordance with OECD Guideline 403, the LC50 was determined to be greater than 5.4 mg/L air in both male and female rats.

Executive summary:

In an acute inhalation toxicity study conducted according to OECD Guideline 403, groups of SPF-reared, Wistar derived rats (n= 5/sex) were exposed to a concentration of approximately 5.4 mg ethyl lactate/L for 4 hours and were observed for 15 days. All animals survived until the end of the study. A decreased breathing rate was observed during exposure. 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 the next day. All animals appeared normal for the remainder of the 15 day observation period and gained weight in a normal way. At necropsy, gross-examination 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 maximum attainable concentration due to the physical properties of the test material. Based on these results, the LC50 of ethyl lactate is determined to be greater than 5.4 mg/L. Therefore, classification for acute inhalation toxicity according to CLP Regulation 1272/2008 is not warranted.

This acute inhalation study is classified as acceptable. It does satisfy the guideline requirement for an acute inhaltion study (OECD TG 403) in rats.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 5 400 mg/m³ air

Physical form:

inhalation: aerosol

Quality of whole database:

Guideline study

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study conducted according to OECD guideline 401, groups of Wistar rats (5/sex) were given Ethyl (S)-lactate (99.5% purity) as a single oral dose of 2000 mg/kg bw. No mortality occurred and an oral LD50 value of greater than 2000 mg/kg bw, both in male and female rats, was determined in this study.

No study is available elucidating the acute toxicity of the target substance after inhalation. Thus, available data from the racemat Ethyl lactate was used. In this acute inhalation toxicity study, young adult Wistar rats (5/sex), were exposed to Ethyl lactate at a concentration of 5.4 mg/L for 4 hours. No mortality occurred and based on the result from this key study, the LC50 is considered to be greater than 5.4 mg/L.

Justification for classification or non-classification

Based on the available data, the target substance Ethyl (S)-lactate does not warrant classification for acute toxicity. The LD50 value for the oral route is above the limit value of the relevant OECD guideline. The LC50 value received from an acute inhalation study conducted with an suitable read-across partner exceed the limit dose of 5.4 mg/L.