Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 April 2010 to 04 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
magnesium dinitrate hexahydrate
Cas Number:
13446-18-9
Molecular formula:
H12MgN2O12
IUPAC Name:
magnesium dinitrate hexahydrate
Constituent 2
Chemical structure
Reference substance name:
Magnesium nitrate
EC Number:
233-826-7
EC Name:
Magnesium nitrate
Cas Number:
10377-60-3
Molecular formula:
HNO3.1/2Mg
IUPAC Name:
magnesium
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): Magnesium nitrate hexahydrate
- Physical appearance: White solid flakes

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8-11 weeks old) were selected.
- Weight at study initiation: 149 - 192 gram. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available.
- Housing: Labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.
- Other:
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 21.5ºC
- Humidity (%): 34 - 60%. Temporary deviations from the minimum level of relative humidity (40%) occurred, but laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN LIFE DATES: From: 14 April 2010 To: 04 May 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Elix, Millipore S.A.S., Molsheim, France
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg test substance / mL vehicle.
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Lot/batch no. (if required): Not indicated.
- Purity: Not indicated.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg.

DOSAGE PREPARATION (if unusual): The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.
Doses:
2000 mg/kg.
Single dosage, on Day 1 via oral gavage using plastic feeding tubes.
No. of animals per sex per dose:
6 ( two subsequent groups of three animals)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (Day 1 - Day 15)
- Frequency of observations and weighing: Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15 (see 'Any other information on materials and methods inc. tables). Body weights: on Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes (see 'Any other information on materials and methods inc. tables).
- Other examinations performed: Mortality: twice daily.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Preliminary study:
Not applicable.
Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
other: LD50 cut-off value
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: According to the OECD423 test guideline
Mortality:
No mortality occurred. See attached document 'Results tables'.
Clinical signs:
Hunched posture and piloerection were observed for all animals on Day 1. See attached document 'Results tables'.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. See attached document 'Results tables'.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals. See attached document 'Results tables'.
Other findings:
Not applicable.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
Based on these results, Magnesium nitrate hexahydrate does not have to be classified and has no obligatory labeling requirement for acute oral toxicity according to the:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.