2-methylpropyl-(R)-2-hydroxypropanoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

1992-06-02 to 1992-07-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Isobutyl-S-lactate used as read-across partner.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

77027-84-0

Cas Number:

77027-84-0

IUPAC Name:

77027-84-0

Constituent 2

Reference substance name:

Isobutyl-(S)-lactate

IUPAC Name:

Isobutyl-(S)-lactate

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report): 2-Methyl-propyl-(S)-lactate
- Chemical name: (S)-2-hydroxypropanoic acid, 2-methylpropyl ester
- Analytical purity: 99.7 %
- Molecular formula (if other than submission substance): C7H14O3
- Lot/batch No.: PSP-IBL-01
- Flash point: 70 °C
- Boiling Point: 455 K at 1.0E+05 Pa
- Density: 0.979 kg/L at 293 K

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wistar rats, Crl:WI(WU)BR
- Age at study initiation: 10-11 weeks (5-6 when delivered + 35 days acclimatisation)
- Weight at study initiation: Mean weight of male rats 278 g and female rats 174 g.
- Housing: The animals were housed in an animal room, 5 per cage.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 35 days
- Fasting: during exposure the animals were deprived of food and water
ENVIRONMENTAL CONDITIONS
Due to technical problems, no check for temperature and humidity was conducted in the period of 14 to 18 May 1992.
- Temperature (°C): 21.0 to 24.0
- Humidity (%): 34 to 71, the relative humidity was between 70 and 83 % at one day and up to 92 % during short periods due to cleaning activities.
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation-chamber from ADG Developments LTD.
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: Plastic animal holder (Battelle)
- Source and rate of air: Compressed with a mean air flow through the test chamber of 37.6 L/min (2.3 m³/h)
- System of generating particulates/aerosols: Atomizer (DR 011, Lechler)
- Method of particle size determination: 11-stage cascade impactor
- Temperature and humidity in air chamber: Temperature and relative humidity has been monitored with a digital thermohygro-monitor (type DAL-02, Novasina AG) and recorded 7 times during the exposure at regular intervals. Temperature was held at 21.7 ± 0.1 °C and relative humidity was below 1 %.

TEST ATMOSPHERE
- Brief description of analytical method used: The actual concentration of 2-methyl-propyl-(S)-lactate in the test atmosphere was determined once each hour by means of gas chromatographic analysis (Vega). The concentration of the test substance in the test atmosphere has been validated once an hour. Therefore, 10 L test atmosphere was passed at 2 L/min through acetone in an impinger, kept at 4 °C. Filled up to 50 ml in a volumetric flask, the sample was then tested using GC. To determine the concentration of 2-methyl-propyl-(S)-lactate in the test atmosphere samples, the peak area of the 2-methyl-propyl-(S)-lactate peak was compared with that of a standard solution containing 105.3 mg 2-methyl-propyl-(S)-lactate in 100 ml acetone, corresponding to a concentration level of 10.53 g 2-methyl-propyl-(S)- lactate per m³ air. The nominal concentration of 2-methyl-propyl-(S)-lactate was determined by dividing the total amount of test material used by the total volume of air passed through the exposure device. Particle size distribution measurement was carried out once using an 11-stage cascade impactor.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Once per hour via gas chromatography

Duration of exposure:

4 h

Concentrations:

Target concentrations: 5 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 observations: Before, during and shortly after exposure, as well as once a day during the observation period.
- Body weight: Before exposure and at day 7 and 14
- Necropsy of survivors performed: Yes

Statistics:

N.A.

Results and discussion

Preliminary study:

N.A.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6 160 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occurred.

Clinical signs:

other: During exposure, the breathing patterns of all tested rats changed. Those changes have mostly been a visually noticable decrease in breathing frequency accompanied by signs of post-inspiratory apnoea. In one male and one female rat, the decrease in breath

Body weight:

Normal body weight gain was observed in eight out of ten rats during the observation period. One female rat showed weight loss during the first week, another female rat showed only marginal body weight gain during the second week of observation.

Gross pathology:

No abnormalities were found at necropsy.

Other findings:

Analytical results:
The actual concentrations measured during the exposure to 2-methyl-propyl-(S)-lactate are given in Table 1. The mean actual concentration (and standard deviation) were 6.16 (0.23) g/m³ (Table 1). The nominal concentration was 9.4 g/m³.
Particle size distribution:
The particle size distribution is given in Table 2. The particle size measurement showed that ca. 86 % of the particles had an aerodynamic diameter between 2.4 and 4.2 µm.

Any other information on results incl. tables

Table 1: Actual concentration of 2-methyl-propyl-(S)-lactate in the test atmosphere
Sampling time	Sample no.	Peak area (counts)	Average peak area (counts)	Concentration (g/m³)	Total (g/m³)
Standard solution		795223	792991
		738862
		834753
		803124
9.57	*1-1	164577	162449	1.08	5.91
		160321
	1-2	723596	728293	4.83
		732990
10.57	*2-1	148205	144104	0.96	6.37
		140002
	2-2	819073	815944	5.41
		812815
11.57	*3-1	133891	139593	0.93	6.03
		145295
	3-2	757717	769336	5.10
		780954
12.57	*4-2	124018	125003	0.83	6.30
		125987
	4-2	846954	827766	5.50
		808577
Mean					6.16
SD					0.23

*= content of sampling tube

SD= standard deviation

Table 2: Aerodynamic particle size distribution of 2-methyl-propyl-(S)-lactate test atmosphere
Aerodynamic diameter (µm)		Distribution in % of total mass
< 1.0		0
1.0		0
1.4		0
1.8		0
2.4		5
2.8		20
3.1		18
3.4		11
3.8		27
4.2		5
> 4.2		14

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, the acute inhalation toxicity of 2-methyl-propyl-(S)-lactate, as determined in a study according to OECD guideline 403, exceeds an LC50 (4 h) of 6.16 g/m³.

Executive summary:

In an acute inhalation toxicity study according to OECD guideline 403, groups of young adult Wistar rats (5/sex) were exposed at a limit concentration of  6.16 g/m³ via the inhalation route (nose only) to 2-methyl-propyl-(S)-lactate (99.7% purity) in compressed air for 4 hours. After exposure, the animals were observed for a period of 14 days. No mortality or distinct clinical signs were observed after treatment. Macroscopic examination of the animals at the end of the observation period did not reveal any treatment-related gross changes. As no mortality occurred during the 14-day observation period, the inhalation LC₅₀ of 2-methyl-propyl-(S)-lactate is considered to exceed 6.16 g/m³ in male and female rats.