Registration Dossier

Administrative data

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
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Reference substance name:
Reaction mass of N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide and methacrylic acid
EC Number:
934-058-1
IUPAC Name:
Reaction mass of N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide and methacrylic acid
Test material form:
other: viscous liquid
Details on test material:
- Name of test material (as cited in study report): Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide, Sipomer WAM II
- Storage condition of test material: at room temperature and protected from light

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:
Not applicable: Limit test
Effect levelsopen allclose all
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.

Any other information on results incl. tables

No other information

Applicant's summary and conclusion

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.