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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-07-14 - 1993-07-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl 2-hydroxy-2-methylpropionate
EC Number:
218-301-2
EC Name:
Methyl 2-hydroxy-2-methylpropionate
Cas Number:
2110-78-3
Molecular formula:
C5H10O3
IUPAC Name:
methyl 2-hydroxy-2-methylpropionate
Test material form:
liquid
Details on test material:
- State of aggregation: Colorless transparent liquid
- Density: 1.023 g/cm³ (25°C)
- Flash point: 137°C
- impurity: Water (0.1 wt%)
- Molecular weight: 118.12
- Soluble in water and oil
- Other:

Test animals

Species:
rat
Strain:
other: SD (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc. on July 6, 1993
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 5 weeks
- Weight at study initiation: 119 +/- 4.1 g (males) and 106 +/- 6.8 g (females)
- Fasting period before study: overnight fast from the evening of the previous day
- Housing: 6 - 10 animals per suspension-type metallic cage for rats
- Diet: ad libitum (pellet food for rats (MF; Oriental Yeast Co., Ltd.)
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2°C
- Humidity (%): 55 +/- 6 %
- Photoperiod (hrs dark / hrs light): 12-hr light/12-hr dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5, 5, 10, 20 and 50 (v/v)%
- Amount of vehicle (if gavage): 1.0 mL/100 g of bw

Preparation of dosing solutions
Designated amounts of the test substance were weighed and dissolved in distilled water to prepare 0.5-50 (v/v)% aqueous dosing solutions.
Doses:
50, 500, 1000, 2000 and 5000 mg/kg bw
No. of animals per sex per dose:
6 males per dose (50, 500, 1000, 2000 and 5000 mg/kg bw)
6 females per dose (50, 500, 1000, 2000 and 5000 mg/kg bw)
Control animals:
yes
Remarks:
distilled water, 1.0 mL/100 g of body weight
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: Day 0 immediately before administration and Days 2, 7, and 14 using an electronic balance (Model 1219 MP, Carl Zeiss)
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
No preliminary study performed.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 - <= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Four males and 5 females from the 5000 mg/kg group died within 24 hrs after administration.
No other animal from any other group died.
Clinical signs:
Among males, staggering gait occurred in two animals from the 5000 mg/kg group 5 min after administration. These animals showed increased body muscle tone and died 10 min after administration. Other animals started to show sedation and body drooping 3 hrs after administration and fell into collapse. Two males died within 24 hrs after administration.
No changes in general signs of symptoms were observed in animals from the 50-2000 mg/kg groups.
Among females, symptoms such as sedation, body drooping and staggering began to be seen in the 5000 mg/kg group about 30 min after administration. Animals then fell into collapse and 5 females died within 24 hrs.
Body weight:
Body weight decreased in females from the 5000 mg/kg group on Day 2, but their weight gain was normal thereafter. Males showed no abnormality.
Gross pathology:
Dead males and females showed congestion and hemorrhage in the lungs and white color changes in the liver and duodenal mucosa. However, surviving males and females showed no particular abnormality at the end of the study.

Any other information on results incl. tables

Table 1: Mortality of rats

Sex Dose
(mg/kg)
Days after administration Final
death
rate
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Male 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
50 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
500 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
1000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
2000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
5000 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4/6
Female 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
50 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
500 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
1000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
2000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/6
5000 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5/6

Table 2: General signs and symptoms

  Dose
(mg/kg)
Staggering Body
muscle
tone
Sedation Body
dropping
Collapse
Male 0 0/6 0/6 0/6 0/6 0/6
50 0/6 0/6 0/6 0/6 0/6
500 0/6 0/6 0/6 0/6 0/6
1000 0/6 0/6 0/6 0/6 0/6
2000 0/6 0/6 0/6 0/6 0/6
5000 2/6 2/6 2/4 2/4 2/4
Female 0 0/6 0/6 0/6 0/6 0/6
50 0/6 0/6 0/6 0/6 0/6
500 0/6 0/6 0/6 0/6 0/6
1000 0/6 0/6 0/6 0/6 0/6
2000 0/6 0/6 0/6 0/6 0/6
5000 1/6 0/6 5/6 6/6 1/2

Number of animals with findings/Number of surviving animals

Applicant's summary and conclusion

Interpretation of results:
other: CLP criteria not met
Conclusions:
The test substance methyl 2-hydroxyisobutyrate was considered weakly toxic in rats. The test item does not meet the classification criteria of Regulation (EC) No. 1272/2008 (CLP Regulation).
Executive summary:

An oral acute toxicity study of methyl 2-hydroxyisobutyrate was conducted in rats according to OECD Guideline 401.

Briefly, the test substance methyl 2-hydroxyisobutyrate was administered by gavage to male and female SD rats (SPF) to determine its lethal dose and evaluate its acute toxicity.

The LD50 was estimated to be 2,000-5,000 mg/kg in both males and females.

In the monitoring of general signs and symptoms, both males and females from the 5000 mg/kg group showed staggering gait 5-30 min after administration. Two males from this group died 10 min after administration after showing increased body muscle tone. Other males and females gradually showed sedation and body drooping, and some of them died within 24 hrs after showing collapse.

Both males and females from the 50-2000 mg/kg groups showed no changes in general symptoms. Body weight decreased in females from the 5000 mg/kg group 2 days after administration, but normal weight gains were observed thereafter. Males showed no abnormality. Necropsy revealed congestion and hemorrhage in the lungs and white color changes in the liver and duodenal mucosa in dead males and females, but surviving animals showed no particular abnormality at the end of the study.

Based on these findings, methyl 2-hydroxyisobutyrate was considered weakly toxic in rats. The test item does not meet the classification criteria of Regulation (EC) No. 1272/2008 (CLP Regulation).

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