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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 June - 01 July 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted and well described study in accordance with GLP and OECD Guideline 423 without any deviation.
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:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Zinc methacrylate
EC Number:
236-144-8
EC Name:
Zinc methacrylate
Cas Number:
13189-00-9
Molecular formula:
C4H6O2.1/2Zn
IUPAC Name:
zinc bis(2-methylacrylate)
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): ZnDMA
- Physical state: White powder
- Analytical purity: 97 %
- Lot/batch No.: 08010301
- Production date: 03 January 2008
- Date of receipt: 02 June 2008
- Expiration date of the lot/batch:03 January 2009
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 190-211 g
- Fasting period before study: Food was removed at Day 1 and then redistributed 4 h after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with stainless steel mesh lids.
- Diet: Food, ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 41-70 %
- Air changes: At least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
- 3 females/dose (2000 mg/kg bw)
- 6 females/dose (300 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
Bodyweight: The animals were weighed on Day 0 (just before administering the test item) then on Days 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels and macroscopic examination was performed.
Statistics:
None

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: All animals were died at 2000 mg/kg bw. No mortality was observed at 300 mg/kg bw.
Mortality:
- All three treated rats were died at 2000 mg/kg bw between 3 and 6 h after the test item administration.
- No mortality was observed at 300 mg/kg bw.
Clinical signs:
- At 2000 mg/kg bw, mortalities were preceded by a decrease of the spontaneous activity (3/3) associated with a decrease of muscle tone (2/2), a decrease or an absence of Preyer's and righting reflex (3/3) and a piloerection (2/2).
- At 300 mg/kg bw, from 30 minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated with a decrease of righting reflex (5/6) and a piloerection (5/6). The animals recovered a normal activity between the 3rd and the 4th day of the test.
Body weight:
- Body weight evolution of the animals remained normal throughout the study.
Gross pathology:
- Macroscopical examination of the animals treated at 2000 mg/kg bw which died during the test revealed a white thickening layer at the level of the corpus.
- No macroscopic abnormalities were observed at 300 mg/kg bw.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the oral LD50 for ZnDMA is 500 mg/kg bw in female rats therefore it is classified as R22 "harmful if swallowed" according to the Annex VI to the Directive 67/548/EEC and classified to "category 4" according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP, groups of Sprague Dawley rats were given a single oral (gavage) dose of ZnDMA at 2000 mg/kg bw (3 females) followed by 300 mg/kg bw (6 females). Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

All three treated rats were died at 2000 mg/kg bw between 3 and 6 h after the test item administration. No mortality was observed at 300 mg/kg bw. At 2000 mg/kg bw, mortalities were preceded by a decrease of the spontaneous activity (3/3) associated with a decrease of muscle tone (2/2), a decrease or an absence of Preyer's and righting reflex (3/3) and a piloerection (2/2). At 300 mg/kg bw, from 30 minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated with a decrease of righting reflex (5/6) and a piloerection (5/6). The animals recovered a normal activity between the 3rd and the 4th day of the test. Body weight evolution of the animals remained normal throughout the study. Macroscopical examination of the animals treated at 2000 mg/kg bw which died during the test revealed a white thickening layer at the level of the corpus. No macroscopic abnormalities were observed at 300 mg/kg bw. In this study, the oral LD50 of test item was considered to be 500 mg/kg bw in female rats.

Under the test conditions, the oral LD50 for ZnDMA is 500 mg/kg bw in female rats therefore it is classified as R22 "harmful if swallowed" according to the Annex VI to the Directive 67/548/EEC and classified to "category 4" according to the CLP Regulation (EC) N° (1272-2008).

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