Registration Dossier

Administrative data

Description of key information

There are data for EMA for oral and inhalation routes. There are no reliable data for EMA for the dermal route although there are data for other members of the lower alkyl methacrylate esters category that are consistent and sufficient to enable an assessment for this endpoint. Available data indicate a very low acute toxicity of EMA.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
acceptable for assessment although with limited documentation
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Version / remarks:
no guideline available at the time of the study
Principles of method if other than guideline:
Pre-dates GLP and existing guidelines
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: albino
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
12700, 14510, 16330 and 18140 mg/kg (single dose)
No. of animals per sex per dose:
10 rats per dose
Details on study design:
 Doses were given via stomach tube to test animals and observed to toxic symptoms and death.
Statistics:
LD50 for rats was calculated by the method of Bliss (1938), but was not reported.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
13 424 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Original value LD50:  14.8 ml/kg = 13424 mg/kg
Mortality:
Deaths in rats were as follows: 3/10  (low dose), 8/10 (next dose), and 10/10 rats at the two highest doses. Rats died within 1-96 hours.
Clinical signs:
Author noted that both species exhibited increased respiratory rate and lacrimation within 2-5 minutes; followed by motor weakness and decreased respiration, increased defecation and urination in 15-40 minutes. Animals which did not survive, died in a coma.

The LD50 estimated by the method of Bliss clearly demonstrates that the test material is of low acute toxicity by the oral route.

Conclusions:
A reliable published acute oral LD50 in rats was 13424 mg/kg bw.
Executive summary:

A reliable published acute oral LD50 in rats was 13424 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
13 424 mg/kg bw

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
DATA QUALITY: Study was conducted in accordance with a recognized scientific procedure for determining the acute inhalation toxicity of a test substance, following GLP regulations. The study meets national and international scientific standards and provides sufficient information to support the conclusions regarding the acute inhalation toxicity of Ethyl Methacrylate.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Crl: CD BR
Sex:
male/female
Details on test animals and environmental conditions:
Young adult male and female Crl:CD BR rats, 8 weeks old,  weighing 240-351 grams (males) and 152-221 grams (females); housed singly  or in pairs by sex. Food and water available ad libitum, except during  exposure.
Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see comment below
Duration of exposure:
4 h
Concentrations:
12.2, 40.4, 48.4 and  57 mg/L
No. of animals per sex per dose:
5 males and 5 females per dose group. 
Control animals:
not specified
Details on study design:
Four groups of five male and five female rats were exposed  nose-only for 4 hours to several concentrations of the test material in  air. The chamber airflow was 25 L/min, the chamber temperature was 23-30  degrees C, and the relative humidity was 31-44%, with 21 percent oxygen.  Test concentrations were generated by 
vaporizing the test material in air  using a heated J-tube. Filtered high pressure air fed through the J-tube mixed with the test substance and was metered into the 29 L glass  exposure chamber. Concentrations were varied by varying the rate of test  substance introduced into the J-tube.  Each group of rats was observed for 
mortality and  clinical signs during exposure and daily throughout the 14 days  post-dosing.  Animals were  weighed daily throughout the study. No  necropsy was conducted.

Analytical verification of test atmosphere concentrations: Atmospheric concentrations were  monitored at 30 min intervals during exposure, by gravimetric analysis  and GC. The chamber vapor concentration was 
determined by comparing the GC response of the test material with calibration standards.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
55 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
 Deaths occurred at 48 mg/L and higher; 1/5 males and 0/5 females at 48  mg/L; and 4/5 males and 2/5 females at  57/L. No deaths occurred at the  other doses.
Clinical signs:
other: Rats exposed to 57 mg/L experienced nasal discharge,  gasping, irregular respiration, lethargy, lung noise, and moderate weight  loss. At 48 mg/L, rats demonstrated oral, nasal and ocular discharge,  gasping, irregular respiration lethargy, lung noise, hu
Body weight:
sporadic weight loss returned to normal by the end of  the study.
Conclusions:
In a valid guideline study acute (4 hr) inhalation LC50 in rats was 55 mg/L.
Executive summary:

In a valid guideline study acute (4 hr) inhalation LC50 in rats was 55 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
55 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral

In the key study (Deichmann, 1941) the LD50 for EMA was determined to be 13424 mg/kg bw.

The study was performed before GLP and OECD guidelines were established and therefore only basic data were available. However, it is broadly consistent with data obtained in other species and with other esters in the category of lower alkyl methacrylate esters and, therefore, the entire data base provided sufficient information to assess the acute oral toxicity.

 

Inhalation

The acute toxic potential of ethyl methacrylate after inhalation exposure in rats is low (LC50 = 55 mg/L 4 h exposure (Kelly, 1993)

 

Dermal

No valid data exist for EMA by the dermal route. Valid data for shorter (MMA) and longer (n-BMA) esters within the category, as well as two early pre-guideline studies (invalid according to Klimisch criteria) on the longest ester (2-EHMA), that are sufficient for the assessment and that indicate low acute dermal toxicity.

 

Other routes

There are studies for toxicity using other routes of exposure (i.p.,) using different species which are not considered being relevant for the assessment.

  

Justification for classification or non-classification

EMA is of low acute toxicity by the oral and inhalation routes. By analogy to shorter and longer esters of the lower alkyl methacrylate ester category EMA is considered to be of low dermal toxicity. Based on the available information ethyl methacrylate is not required to be classified for its acute toxicity potential according to 67/548/EEC and UN-GHS requirements, respectively.