Methyl 2-((allyloxy)methyl)acrylate

Endpoint summary

Description of key information

Acute toxicity, oral, (rat): 300 mg/kg bodyweight < LD50 < 2000 mg/kg bodyweight

Acute toxicity, inhalation, (rat): LC50 1.087mg a.i/L air

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:

16 Apr 2013 - 13 Jun 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

- Supplier : Orient Bio Co., Ltd. 699-13, Mokdong-ri, Buk-myeon, Gapyeong-gun, Gyeonggi-do, Korea
- Number of animals and sex distinction at the time of receipt : 14 females
- A range of age and body weight at the time of receipt : 8 weeks old, 174.8 g ~ 186.2 g
- A range of age and body weight at the time of administration : 9 weeks old, 180.0g ~ 182.8 g (1st step), 181.7 g ~ 188.2 g (2nd step), 10 weeks old, 190.3 g ~ 197.1 g (3rd step)


- Housing: stainless stell cage
- Diet:ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ±2 0
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:

300, and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 4 hours after treatment and then daily for 14 days
- Frequency of observations and weighing: Body weight was measured at animal receipt day, animal allocation day, just before treatment and on day 7 and 14 after the administration. Body weight of dead animal was also measured when it was found to be dead.
- Necropsy of survivors performed: yes

Preliminary study:

not specified

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All the animals died in 3rd step(2000 mg/kg body weight), two (Animal No. : 2302, 2303) animals on day 1 and one (Animal No. : 2301) animal on day 2 after adminstration. No mortality was observed in the 1st and 2nd step (300 mg/kg body weight) groups.

Clinical signs:

other: Clinical signs related with the substance, the salivation, inanimation and prone position, were observed from 2 hour to day 1 in 3rd step (2000 mg/kg) dose group. No clinical signs was observed in 1st and 2nd step (300 mg/kg) groups. Clinical signs were c

Gross pathology:

In necropsy finding of died animals, test substance retention in the stomach were observed in all (Animal No. : 2301 ~ 2303) died animals. There were no necropsy findings caused by administration of test substance in all survived animals.

Other findings:

not specified

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results, the 2-(Allyloxymethyl) acrylic acid methyl ester was classified in to GHS (Globally Harmonized Classification System for Chemical Substances and Mixtures) Category 4 (300 mg/kg body weight < LD50 < 2000 mg/kg body weight) in this study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

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:

22nd August 2018 - 13th October 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal breeding facility. Jai Research Foundataion.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9-11weeks
- Weight at study initiation: Male: 311.3g - 377.3g Female: 172.9g - 215.7g
- Fasting period before study: Not specified.
- Housing: Maximum 3 rats of same sex/cage.
- Historical data:
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: 7 to 9 days. Rats were also acclimatised for a period of 4h one day prior to exposure in the rat restrainer tubes.
- Method of randomisation in assigning animals to test and control groups: The censored randomization method. (Gad and Weil, 1994)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 55 to 66%
- Air changes (per hr): Minimum 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark maintained by an automatic timer.

IN-LIFE DATES: 22nd August 2018 - 13th October 2018

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 1 - <= 4 other: microns

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation Chamber.
- Exposure chamber volume: 2.062 Liters
- Method of holding animals in test chamber: Restraint tubes.
- Source and rate of air (airflow): Dynamic air flow rate of 12 air changes per hour and ensure adequate oxygen content of at least 19%.
- System of generating particulates/aerosols: The test item will be aerolized with the help of a spray atomizer or aerosol generator.
- Method of particle size determination: Particle size analysis will be carried out using a cascade impactor by the gravimetric method.
- Temperature, humidity, pressure in air chamber: 22°C. humidity between 30 and 70%.

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: Gravimetric method.
- Samples taken from breathing zone: yes



TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1-4microns

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Initial a study conducted with three male and three female rats. 100% mortality was observed in exposed rats at the breathing zone concentration of 5.276mg a.i/Lair, it was considered a sighting study. The full study was then conducted at three dose levels 2.407, 2.17 and 0.829 mg a.i/L air.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Breathing zone concentrations were 2.407, 2.107 and 0.829 mg a.i/L air.

No. of animals per sex per dose:

Three groups of rats, consisting of five males and five females per group used in the main study.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice a day.
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.087 mg/L air

Based on:

test mat.

95% CL:

> 0.776 - <= 1.523

Exp. duration:

4 h

Remarks on result:

other: This is a calculated value. Due to a mortality pattern observed, determination of a separate LC50 value for male and female rats was not possible.

Mortality:

Percent mortalities (both sexes combine) were observed 100, 90 and 30 at the breathing zone concentrations 2.407, 2.17 and 0.829 mg a.i/L air respectively.

Clinical signs:

lethargy (hypoactivity)

Body weight:

In groups 2 and 3 a decrease in body weight was noted however increased at day 14 when compared to Body weight on day 0.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Percent mortalities (both sexes combine) were observed 100, 90 and 30 at the breathing zone concentrations 2.407, 2.17 and 0.829 mg a.i/L air respectively.
Based on the results of this study, an indication of the classification for FX-AO-MA is as follows:

Category 4: H332: Harmful if inhaled

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An acute oral toxicity study was conducted (Healthcare Research Laboratory, 2013, Study TBK-0202 (KG-2013-141)) to assess the toxicity of 2-(Allyloxymethyl) acrylic acid methyl ester following a single oral administration. The study was conducted in accordance with OECD guidelines 423 and in compliance with GLP.

 

In accordance with the method, the 2-(Allyloxymethyl) acrylic acid methyl ester was administered at the dose levels of 300, 300 and 2000 mg/kg (steps 1, 2 and 3, respectively) by oral gavage. Three animals were used per dose group. As all the rats at 2000 mg/kg dose level died, no further rats were dosed at 2000 mg/kg. No rats in the first two group died at 300 mg/kg.

 

It was concluded that the acute median lethal dose in rats following oral administration of 2-(Allyloxymethyl) acrylic acid methyl ester was between 300 mg/kg and 2000 mg/kg.

 

An acute inhalation toxicity study was conducted (Jai Research Foundation, 2018, Study (405-1-01-20539) to assess the toxicity of 2-(Allyloxymethyl) acrylic acid methyl ester following a 4 hour nose only inhalation exposure. The study was conducted in accordance with OECD guidelines 403 and in compliance with GLP.

 In accordance with the method, rats were exposed to 2-(Allyloxymethyl) acrylic acid methyl ester breathing zone concentrations of 2.407, 2.107 and 0.829 mg a.i/L air by nose only exposure. Ten animals were used per dose group. Clinical signs of toxicity abdominal breathing was observed in rats exposed to breathing zone concentrations of 2.407 mg a.i/L air while abdominal breathing and lethargy were observed in rats exposed to, 2.107 and 0.829 mg a.i/L air.

Percent mortalities (both sexes combined) were 100, 90 and 30 at the breathing zone concentrations 2.407, 2.107 and 0.829 mg a.i/L air respectively that indicates dose dependent mortality.

It was concluded that the acute median lethal concentration in rats following inhalation of 2-(Allyloxymethyl) acrylic acid methyl ester was 1.087 mg a.i/L air.

Justification for classification or non-classification

The acute oral LD50 was determined to be between 300 - 2000 mg/kg, and on this basis 2-(Allyloxymethyl) acrylic acid methyl ester was classified as H302 "Harmful if swallowed", and 2-(Allyloxymethyl) acrylic acid methyl ester is classified as acute toxicity category 4.

 

It is acknowledged that under the CLP Regulation, Category 4 for acute oral toxicity applies when the Acute Toxicity Estimate (ATE) / LD50 falls between 300 - 2000 mg/kg (c.f. 2-(Allyloxymethyl) acrylic acid methyl ester LD50 between 300 - 2000 mg/kg), however as no deaths were seen at 300 mg/kg, it is assumed for the purpose of classification that the LD50 is above 300 mg/kg, and that classification in Category 4 is appropriate.

 

The acute inhalation LC50 was determined to be 1.087 mg a.i/L air, and on this basis 2-(Allyloxymethyl) acrylic acid methyl ester was classified as H332 "Harmful if inhaled", and 2-(Allyloxymethyl) acrylic acid methyl ester is classified as acute toxicity category 4.

 It is acknowledged that under the CLP Regulation, Category 4 for acute inhalation toxicity for dusts/mists applies when the Acute Toxicity Estimate (ATE) / LC50 falls between 1 - 5 mg/L air (c.f. 2-(Allyloxymethyl) acrylic acid methyl ester LD50 between 1 - 5 mg/L air), it is assumed for the purpose of classification that the LD50 is between 1-5 mg/L air, and that classification in Category 4 is appropriate.