Butyl (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 butyl-S-lactate (> 97% purity) as a single oral dose of 2000 mg/kg bw in maize oil. 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 toxicity study, young adult Wistar rats (5/sex), were exposed by nose-only inhalation to aerosols of butyl-S-lactate at a concentration of 5.14 g/L in air for 4 hours. 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:

August 1989 to 1989-11-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted in Feb 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name used in the study report: (S (-) - Butyl lactate)
- Trade Name: Purasolv BL
- Batch No.: BU 021F
- Purity: min. 97%
- Appearance: clear, colourless liquid
- CAS No.: CAS: 138-22-7 (although this is the CAS number for butyl lactate of unspecified stereochemistry, the substance is clearly identified as the S-enatiomer)

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding Center for Laboratory Animals 'Charles River Wiga GmbH, Sulzfeld, F.R., Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: 161-188 g for males and 126-139 g for females
- Number of animals: 5 females, 5 males
- Housing: in groups of 5 animals, stainless cages with wire-screen bottom
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

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

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 % (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: No data

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

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. At the end of the observation period, the rats were killed for macroscopic examination. No microscopic examination was performed.

Statistics:

No data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: At 1, 4 and 24 h after treatment all animals showed moderate piloerection, which was not observed 48 h afterwards. At 4 h post treatment all animals showed moderate signs of diarrhoea, which were not observed 24 h after treatment.

Gross pathology:

No treatment-related gross lesions were observed.

Other findings:

No other findings

Table 1: Summary of dose applied, mortality and mean body weights on day 0, 3, 7 and 14 after exposure to butyl-S-lactate:

Sex	Test concentration [mg/kg]	Mean body weight [g] on day				Mortality per 5 animals
		0	3	7	14
Male	2000	174	324	238	267	0/5
Female	2000	131	156	163	172	0/5

Interpretation of results:

GHS criteria not met

Conclusions:

Butyl-S-lactate is not acutely toxic when administered to rats by gavage, at a single dose of 2000 mg/kg bw. The LD50 is greater than 2000 mg/kg bw for both sexes.

Executive summary:

In an acute oral toxicity study conducted according to OECD guideline 401, groups of Wistar rats (5/sex) were given butyl-S-lactate (min. 97 % purity) as a single oral dose of 2000 mg/kg bw in maize oil. The animals were observed for 14 days after the single exposure. No mortalities occurred. Therefore, the oral LD50 value is greater than 2000 mg/kg bw, both in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Guideline study

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

Study period:

July 1991 to 1995-08-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted May 1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Specific details on test material used for the study:

- Name: n-butyl-S(-)-2-hydroxy propionate
- Purity: > 97%
- Appearance: Clear liquid
- CAS: 138-22-7 (although this is the CAS number for butyl lactate of unspecified stereochemistry, the substance is clearly identified as the S-enatiomer)
- Storage: room temperature

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding Center for Laboratory Animals, Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 7-8 weeks
- Mean weight at study initiation: 212 g for males and 163 g for females
- Housing: 5 males or females/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19–21.5
- Humidity (%): On several days the relative humidity fluctuated between 70 and 80 %. Higher values (up to 88 %) were reached for short periods of time, due to cleaning activities.
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remark on MMAD/GSD:

See Table 1 in box "Any other information on results incl. tables".

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber: consisted of a 5-sections cylindrical aluminium column (ca. 60 L) surrounded by a transparent PVC cylinder
- Method of holding animals in test chamber: plastic animal holders (Battelle)
- System of generating particulates/aerosols: The test atmosphere was generated by atomizing the test material into small droplets by using a compressed air driven nebulizer of the Institute's design. The nebulizer consisted of an atomizer and a glass jar, containing the test material. The atomizer coded DR Oil, was purchased from Lechler (Germany). The nebulizer was operated at a pressure of 1.0 bar. During operation, the test material was drawn through a sucking pipe to the atomizer. The generated spray was blown against a baffle which was fitted approximately 8 cm below the nozzle orifice to remove the larger droplets. The impacted test material was drained back into the test material supply at the bottom of the jar. The resulting aerosol was passed from the glass jar to the inlet of the exposure unit. From there it was directed downward through the mixing chambers towards the animal noses. At the bottom of the unit the test atmosphere was exhausted.
- Method of particle size determination: by using an 11-stage cascade impactor
- Total air flow: 1.5 m³/h
- Temperature, humidity, pressure in air chamber: The mean temperature was 20.7 ± 0.1 °C. Relative humidity was less than 1 %.

TEST ATMOSPHERE
- Brief description of analytical method used: The actual concentrations of the test atmosphere were determined once every hour by GC
- Samples taken from breathing zone: No

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: See Table 1 in box "Any other information on results incl. tables".

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

5 g/m³ (target concentration), the analytically verified concentration was 5.14 g/m³

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: before, during and after exposure, and once daily during the observation days
- Weighing: recorded prior to exposure and at days 7 and 14
- Necropsy of survivors performed: yes, at the end of the observation period, surviving rats were killed by exsanguination from the abdominal aorta under ether anaesthesia. All rats were autopsied and examined for gross pathological changes.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.14 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occured.

Clinical signs:

other: During exposure, visually decreased breathing frequency and wet nose and head were observed in all animals to the same extent. Immediately after exposure, visually decreased breathing frequency and wet head were still present. A wet fure was observed in a

Body weight:

Normal body weight gain was observed in all rats during the observation period (see Table 2 in box "Any other information on results incl. tables").

Gross pathology:

No treatment-related lesions were detected after the examination.

Analytical results:

Mean actual concentration (and standard deviation) turned out to be 5.14 (0.13) g/m³. Particle size distribution is given below in Table 1.

Table 1: Aerodynamic particle size distribution of n-butyl-S-(-)-lactate test atmosphere

Aerodynamic diameter (µm)	Distribution in % total mass
< 1.0	0.0
1.0	0.3
1.4	1.1
1.8	1.5
2.4	6.5
2.8	20.0
3.1	20.7
3.4	31.2
3.8	9.0
4.2	2.4
> 4.2	7.2

Body weight:

Normal body weight gain was observed in all rats during the observation period.

Table 2: Individual and mean body weights of male and female rats exposed to n-butyl-S-(-)-lactate aerosols for 4 h.

	Body weight (g)
	Males			Females
	Day 0^a	Day 7	Day 14	Day 0^a	Day 7	Day 14
	209	235	272	169	176	192
	222	234	265	167	177	191
	213	239	270	167	170	183
	221	238	271	160	163	174
	193	209	239	153	157	169
Mean	212	231	263	163	168	182

^a: just before exposure

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute inhalation toxicity study in rats, conducted in accordance with OECD test guideline 403, no mortality occurred. Based on the results, the 4 h inhalative LC50 for n-butyl-S-(-) lactate can be considered to be greater than 5.14 mg/L in rats.

Executive summary:

In an acute inhalation toxicity study, young adult Wistar rats (5/sex), were exposed by nose-only inhalation to aerosols of n-butyl-S-(-)-lactate (> 97% purity) at a concentration of 5.14 mg/L in air, one single time for a period of 4 hours. Animals were observed for 14 days. No mortality occurred. Clinical observations revealed visually decreased breathing frequency, wet head and/or fur, during and shortly after exposure. No abnormalities were observed during the 14-day observation period. All rats showed normal body weight gain during the observation period. No gross lesions were detected at necropsy. Since no mortality occurred during the entire observation period, the LC₅₀ can be considered to be greater than 5.14 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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 butyl-S-lactate (> 97% purity) as a single oral dose of 2000 mg/kg bw in maize oil. 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 toxicity study, young adult Wistar rats (5/sex), were exposed by nose-only inhalation to aerosols of butyl-S-lactate at a concentration of 5.14 g/L in air for 4 hours. Based on the result from this key study, the LC50 is considered to be greater than 5.14 mg/L.

 

Justification for classification or non-classification

Based on the available data, the target substance Butyl-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 exceed the limit dose of 5.14 mg/L.