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Administrative data

Description of key information

Acute oral toxicity: LD 50 rat combined male and female > 5000 mg/kg bw
Acute dermal toxicity: LD 50 rat > 2780 mg/kg bw

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:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is a screening test but followed international guidance requirements with acceptable restrictions. The stuy method was similar to the OECD 401 Guideline.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: no certificate of analysis, no necropsy on dead animals, no weighing of dead animals
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: young adult
- Weight at study initiation: male: 216g; female: 206g
- Fasting period before study: overnight prior to dosing
- Housing: individually housed in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES: From: To: no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
not applicable as the substance is administered as supplied

MAXIMUM DOSE VOLUME APPLIED: 4-5 mL
Doses:
5000 mg/kg bw
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 and weighing: observations daily, weighing prior dosing and at death or at the end of the 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights, histopatholog: not examined
Statistics:
Calculation of te LD50 and 95% confidence limits by the method of moving averages, using the tables constructed by Weil.
Preliminary study:
Not applicable: Limit test
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks:
Dose of substance as registered (including residual water necessary for the stability and impurities)
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks:
Dose of substance as registered (including residual water necessary for the stability and impurities)
Remarks on result:
other: 0/5 males died
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Remarks:
Dose of substance as registered (including residual water necessary for the stability and impurities)
Remarks on result:
other: 3/5 females died within 48h of dosing
Mortality:
3 females died within 48 hours of dosing.
Clinical signs:
Animals appeared sickly following dosing.
Body weight:
Males gained weight normally after dosing (mean of 119g for all males) whereas the surviving females gained weight but in a lesser extent (58 and 40 g gained at the end of the observation period for the 2 surviving females).
Gross pathology:
Organs of the thorax and abdomen appeared normal in the survivors.
Other findings:
no other findings

no other information

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified for acute oral toxicity as the LD50 combined male and female in rat is higher than 5000 mg/kg bw.
Executive summary:

In an acute oral toxicity screening study, performed similarly to the OECD guideline No. 401, a group of Sprague Dawley male and female rats (5 animals/sex) was given a single oral dose of Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide (named as DV-2422N in the study report) by gavage at the dose of  5000 mg/kg bw. The test item was administered as supplied (undiluted). Clinical signs, mortality and body weight gain were checked for a period of up to 14 days.All surviving animals were sacrificed at the end of the study and necropsied for gross abnormalities.

 

Oral LD50 rat combined males and females > 5000 mg/kg bw

 

3/5 females died within 48 hours of dosing whereas no male died. Males gained weight normally after dosing (mean of 119g for all males) whereas the surviving females gained weight but in a lesser extent (58 and 40 g gained at the end of the observation period for the 2 surviving females). Organs of the thorax and abdomen appeared normal in the survivors.

 

Under the test conditions, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified for acute oral toxicity according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Screening Study performed similarly to the OECD 401 Guideline (Klimisch score = 2)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 29 March to 09 August 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study without any restriction
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
N° 2011/40
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: male: 360g (range 350 to 369g); female: 238g (range 229 to 253 g)
- Fasting period before study: no
- Housing: housed by five from the same sex in polycarbonate cages with stainless steel lids (Tecniplast 2000P, 2065 cm²) containing autoclaved sawdust. Nylabone was given as enrichment.
- Diet (e.g. ad libitum): ad libitum, SSNIFF R/M-H pelleted maintenance diet, batch No. 5776558 (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): ad libitum, tap water (filtered with a 0.22 µm filter)
- Acclimation period: 5 days for females, 8 days for males

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): 12 cycles/hour of filtered, non-recylced air
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: To: no data
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
test item applied as supplied
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10
- Type of wrap if used: the application site was covered with a hydrophilic gauze pad. The gauze pad was held in place with an aerated hypoallergic dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after removal of the dressing, any residual test item was removed using a dry cotton pad.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the quantity of test item applied to each animal was adjusted according to the body weight recorded on the day of dose application.
- Concentration (if solution): not applicable as the test item is applied as supplied
- Constant volume or concentration used: no

VEHICLE
Not applicable as the test item is applied as supplied
Duration of exposure:
24h
Doses:
2000 mg/kg bw ( in terms of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide content i.e. approximately 2780 mg/kg in terms of registered substance (including residual water necessary for stability and impurities)).
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each animal was checked for mortality and morbidity, frequently during the hours following treatment, then once a day until the end of the observation period. Animals were observed for clinical signs at least once during the first 30 min, periodically during the first 4h and than once a day. The body weight of each animal was recorded the day of group allocation then on the day of treatment and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: a macroscopic post-mortem examination was performed on all animals. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. No microscopic examination was performed.
Statistics:
no
Preliminary study:
Not applicable: Limit test
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
other: Dose adjusted for content of N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide and methacrylic acid
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 780 mg/kg bw
Based on:
test mat.
Remarks:
Dose of substance as registered (including residual water necessary for the stability and impurities)
Mortality:
No unscheduled deaths occured.
Clinical signs:
No clinical signs indicative of a systemic toxicity were observed in any animals. No cutaneous reactions were observed in any animals.
Body weight:
When compared with the historical control data, body weight of the animals was not affected by the test item treatment.
Gross pathology:
The only macroscopic observation was enlarged spleen with irregular surface in a single female. This isolated finding was considered to be incidental and unrelated to the test item application.
Other findings:
No other findings.

No other information

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified for Acute dermal toxicity according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.
Executive summary:

In an acute dermal toxicity study, performed in compliance with the GLP and according to the OECD 402 Guideline, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide was applied undiluted on the clipped and healthy intact skin (area of 10% of the whole body surface) of groups of Sprague Dawley male and female rats (5 animals/sex). 2000 mg/kg of the main consituents (i.e. 2780 mg/kg bw for the registered substance) was applied as a film on the skin. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days. All animals were sacrificed at the end of the study and necropsied for gross abnormalities.

 

Dermal LD50in male and female rats > 2000 mg/kg bw

 

No mortalities occurred in any animals at the tested doses. No clinical signs indicative of a systemic toxicity were observed in any animals. No cutaneous reactions were observed in any animals. When compared with the historical control data, body weight of the animals was not affected by the test item treatment. The only macroscopic observation was enlarged spleen with irregular surface in a single female. This isolated finding was considered to be incidental and unrelated to the test item application.

 

Under the test conditions, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified for acute dermal toxicity according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 780 mg/kg bw
Quality of whole database:
The study is GLP compliant and has a Klimisch score 1.

Additional information

In an acute oral toxicity study performed similarly to the OECD 401 Guideline, a group of Sprague Dawley male and female rats (5 animals/sex) was given a single oral dose of undiluted Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide by gavage at the dose of  5000 mg/kg bw (test material as registered i.e. including impurities and resudual water necessary for the stability)

. 3/5 females died within 48 hours of dosing whereas no male died. Males gained weight normally after dosing whereas the surviving females gained weight but in a lesser extent. Organs of the thorax and abdomen appeared normal in the survivors. The LD50 combined males and females was therefore determined to be higher than 5000 mg/kg bw.

In a GLP-compliant acute dermal toxcitiy study performed according to the OECD 402 Guideline, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide was applied undiluted on the skin of groups of Sprague Dawley male and female rats (5 animals/sex) at the single dose of 2780 mg/kg bw (test material as registered i.e. including impurities and resudual water necessary for the stability). No mortalities occurred in any animals at the tested dose. No clinical signs indicative of a systemic toxicity were observed in any animals. No cutaneous reactions were observed in any animals and body weight of the animals was not affected by the test item treatment. The only macroscopic observation was enlarged spleen with irregular surface in a single female. This isolated finding was considered to be incidental and unrelated to the test item application. The LD50 was therefore determined to be higher than 2780 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
Based on the physico-chemical properties (low vapour pressure of the main constituents of the registered substance) and unlikely aerosol formation, the inhalation route was not considered the most appropriate for the second acute toxicity study.

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008 including ATP3.

Self classification:

Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified for the acute oral and dermal toxicity according to the Regulation (EC) 1272/2008 (CLP) and to the Directive 67/548/EEC as the oral and dermal LD50 (rats) are higher than 2000 mg/kg bw.

No classification for the acute inhalation toxicity is proposed due to a lack of data.