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Description of key information

With magnesium nitrate (hexahydrate) the acute oral toxicity study with rats showed an LD50 >2000 mg/kg bw. No reliable acute dermal toxicity study with magnesium nitrate is present, however a dermal toxicity study in rats with potassium nitrate showed an LD50 >5000 mg/kg bw. An acute inhalation study is not required due to the low vapour pressure and the high particle size of magnesium nitrate (hexahydrate). The read-across rationale can be found in the document attached in the appropriate target record.

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:
14 April 2010 to 04 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
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
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).
Preliminary study:
Not applicable.
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.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has klimisch code 1.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was performed with a substance analogue and the data are read across.
Justification for type of information:
As the target substance is a nitrate, read-across can be applied using nitric acid, potassium calcium salt as the source substance. The read-across rationale can be found in the document attached under 'Attached justification'.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
all animals survived
Clinical signs:
all animals appeared active and healthy
Body weight:
all animals gained weight
Gross pathology:
Gross pathology: All animals survived, gained weight and appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. No gross abnormalities were noted for the animals necropsied at the conclusion of the 14-day observation period.

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
LD50 > 5,000 mg/kg. The obtained result can be read across to magnesium nitrate.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The study has been performed according to OECD and/or EC guidelines and according to GLP principles. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Additional information

The acute oral toxicity study in rats was performed recently according to OECD, EC, EPA and JMAFF test guidelines with magnesium nitrate (hexahydrate) itself. No mortality, no bodyweight effects and no effects on gross pathology. Hunched posture and piloerection were observed for all animals on Day 1. Therefore the LD50 was determined to be >2000 mg/kg bw.

No reliable study with magnesium nitrate is available for the dermal route of exposure. The acute dermal toxicity study in rats performed according to OECD 402 with potassium nitrate, a read across substance, showed also and LD50 value >5000 mg/kg bw. No effects of toxicity were observed, no mortality, no clinical signs, no effect on bodyweight or on gross pathology.

A study for the inhalation route of exposure is not required, as magnesium nitrate (hexahydrate) has a very low vapour pressure and in addition has a high particle size (only 10% of the particles is smalles than 200 micrometer), so only a negligible fraction might be inhaled via particles. Inhalation exposure is therefore very unlikely.

Justification for selection of acute toxicity – oral endpoint

One acute oral study is available.

Justification for selection of acute toxicity – dermal endpoint

One acute dermal study on the read-across substance potassium nitrate is available.

Justification for classification or non-classification

Justification for classification or non classification (magnesium nitrate)

Based on the available data, magnesium nitrate does not have to be classified according to the CLP Regulation with regard to acute toxicity.

Justification for classification or non classification (aqueous solution)

It is considered justified to use the formula presented in CLP section 3.1.3.6.1 for all 3 exposure routes, although magnesium nitrate and calcium nitrate have not been studied for their acute inhalation toxicity. The mixture is an aqueous solution. Magnesium nitrate and calcium nitrate are not volatile and have a very low vapor pressure. It is not considered justified to assume that vapor from these substances need to be taken into account, also given their high solubility in water and their low acute oral and dermal toxicity.

Applying the formula presented in CLP section 3.1.3.6.1., the ATE (oral) of 500 mg/kg bw for calcium nitrate and the ATE (inhalation) of 2.65 mg/L for nitric acid, the following classification is obtained:

Acute oral toxicity: non-classified (ATEmix: 10 g/kg bw at 5% calcium nitrate)

Acute dermal toxicity: non-classified

Acute inhalation toxicity: non-classified (ATEmix: 53 mg/L at 5% nitric acid)