(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 February 2020 - 31 March 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 433 (Acute Inhalation Toxicity: Fixed Concentration Procedure)

Version / remarks:

2018

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

EC Number:

807-159-2

Cas Number:

69701-99-1

Molecular formula:

C10H16O4

IUPAC Name:

(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Appearance: Colorless liquid
- Storage conditions: Room temperature and protected from light
- Lot number: 09892803
- Purity: 98.8% (excludes optical isomer)
- Expiration date: 15 February 2023

Test animals

Species:

rat

Strain:

other: [Crl:CD (SD)IGS Rats

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories; Raleigh, North Carolina 27610
- Rationale for use of males: OECD 433 guideline
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 256 to 295 grams
- Housing: Polycarbonate cages with a stainless steel mesh lid.
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light):12 hour light/dark cycle

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remark on MMAD/GSD:

Group MMAD (µm) Range
1 2.7 1.75 – 1.82
2 3.6 1.92 – 1.94

Details on inhalation exposure:

Restraint was required for nose only exposure. Animals were restrained (individual plastic exposure tube) during the exposure administration procedures (4 hours = 240 minutes). Animals were also restrained in tubes for up to 10 minutes each before and after exposure, during which time each animal was loaded into and out of the cones. The total time of restraint was expected to be up to a maximum of 260 minutes including the exposure time. The animals were habituated to the method of restraint once for 30 to 60 minutes preceding their test article exposure.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

Nominal: 1.0 and 5.0 mg/L
Measured: 0.942 and 5.607 mg/L
Mean achieved gravimetric concentration was below target by 6% for Group 1.
Mean achieved gravimetric concentration was above target by 12% for Group 2.

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: hourly during exposure, upon return to cage and hourly up to 2 hours after test article administration, then twice daily
- Frequency of weighing: once pretest and again on Days 1 (prior to exposure), 4, 8 and 15
- Observations involved: general condition, skin and fur, eyes, nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration
- Necropsy of survivors performed: yes
- Other examinations performed: Special attention was paid to the lungs and respiratory tract for signs of irritancy and local toxicity

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 0.942 - < 5.607 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Five unscheduled deaths occurred. All 5 animals in the 5.0 mg/L exposure group were euthanized for welfare reasons on Days 1 or 2 of the exposure period due to MEDOL-10-related marked breathing impairment. Relevant macroscopic findings included gaseous distension of the gastrointestinal tract (stomach, small intestine and/or large intestine) and were considered to be secondary to aerophagia.

Clinical signs:

salivation

Body weight:

The animals exposed to 1.0 mg/L of test article showed normal weight gains during the 14 days after exposure.
The animals exposed to 5.0 mg/L of test article did not have body weights measured after exposure

Gross pathology:

Macroscopic changes at 1.0 mg/L were limited to red discoloration of the thymus in 1 male. The finding was considered incidental and not related to MEDOL-10 exposure.

Other findings:

Clinical Observations
The animals exposed to 1.0 mg/L of test article showed no test article-related clinical signs during or after exposure.
The animals exposed to 5.0 mg/L of test article showed no test article-related clinical signs during the exposure but showed excessive salivation, decreased activity and wet rales soon after the exposure. As a result of worsening conditions, 4 of 5 animals were euthanized on the day of exposure and the 5th animal was euthanized on the morning after exposure.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The lethal concentration in 50 percent of the animals (LC50) would be estimated to be >0.942 mg/L but <5.607 mg/L.

Executive summary:

Introduction-

The purpose of this study was to investigate the acute inhalation toxicity of MEDOL-10 and, if appropriate, allow the use of serial steps of Fixed Concentration Procedure (FCP) to provide a ranking of test article toxicity. Data from this study was primarily used to
classify and label the test article in accordance with the United Nations (UN) Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Results-

Five unscheduled deaths occurred. All 5 animals in the 5.0 mg/L exposure group were euthanized for welfare reasons on Days 1 or 2 of the exposure period due to MEDOL-10-related marked breathing impairment. Relevant macroscopic findings included gaseous distension of the gastrointestinal tract (stomach, small intestine and/or large intestine) and were considered to be secondary to aerophagia.

Conclusion-

Thus, the lethal concentration in 50 percent of the animals (LC50) would be estimated to be >0.942 mg/L but <5.607 mg/L which would categorize the test article as GHS Category 4.