Butyl (S)-2-hydroxypropionate

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Butyl (S)-2-hydroxypropionate

EC Number:

252-036-3

EC Name:

Butyl (S)-2-hydroxypropionate

Cas Number:

34451-19-9

Molecular formula:

C7H14O3

IUPAC Name:

butyl 2-hydroxypropanoate

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

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.