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Description of key information

No reliable skin irritation study with magnesium nitrate is present. In a reliable study with ammonium nitrate (OECD 404) no irritation was observed. The read-across rationale can be found in the document attached in the appropriate target records.

An in vivo eye irritation study according to OECD guideline 405 with magnesium nitrate (hexahydrate) itself does not show irritation in rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Sufficient information on the M&M is available to determine the reliability. The study has been performed according to OECD and/or EC guidelines. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Remarks:
study performed before GLP was in place.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Bantin and Kingman Ltd., The Field Station, Grimston, Aldbrough, Hull, HU11 4QE
- Weight at study initiation: 2.72-3.23 kg
- Housing: individually in grid floor cages
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum):free access
- Acclimation period: at least 3 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 C
- Humidity (%): 44-53%
- Air changes (per hr): single air conditioned
- Photoperiod (hrs dark / hrs light):14 hours artificial light (06.00-20.00)
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
water
Controls:
other: each animal served as its own control
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): 0.5 g moistened with water
Duration of treatment / exposure:
4 hours
Observation period:
up to 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: covered with gauze patch and plastic collar around the neck


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towel moistened with water.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
5
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
5
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
5
Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) 1272/2008
Conclusions:
P0018 (ammonium nitrate) was regarded as non-irritant to rabbit skin.
Endpoint:
skin irritation / corrosion, other
Remarks:
not specified
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
GLP compliance:
not specified
Interpretation of results:
other: irritating
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 07 - March 21, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Belton, Leics, England; Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used within the study were at least 6 weeks old *
- Weight at study initiation: body weights were at least 1.0 kg *.
- Housing: Individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Uden, The Netherlands) were available during the study period.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimatization period: at least 5 days before start of treatment under laboratory conditions.

* Animal specifications (sex, age and body weight) are specified in the attached table.

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.

Results of analysis for diet (nutrients and contaminants), hay and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5-20.5ºC
- Humidity (%): 40 - 71%
Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN LIFE DATES: 07 February 2001 and 07 March 2011
Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit):
average 57.5 mg (range: 57.2 mg – 57.9 mg) (a volume of approximately 0.1 mL)
Duration of treatment / exposure:
Single instillation on Day 1.
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 and 14 days after instillation of the test substance.
Number of animals or in vitro replicates:
3 males
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 4 weeks later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Animals were treated by instillation of, the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.

Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
-Washing (if done): No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation:
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
0: No ulceration or opacity (may include slight dulling of normal luster)
1: Scattered or diffuse areas of opacity, details of iris clearly visible
2: Easily discernible translucent area, details of iris slightly obscured
3: Nacreous area, no details of iris visible, size of pupil barely discernible
4: Opaque cornea, iris not discernible through the opacity

Area of cornea involved:
0: No ulceration or opacity
1: One quarter or less but not zero
2: Greater than one quarter, but less than half
3: Greater than half, but less than three quarters
4: Greater than three quarters, up to whole area

IRIS
0: Normal
1: Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive)
2: No reaction to light, hemorrhage, gross destruction (any or all of these)

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
0: Blood vessels normal
1: Some blood vessels definitely hyperaemic (injected)
2: Diffuse, crimson color, individual vessels not easily discernible
3: Diffuse beefy red

Chemosis (refers to lids and/or nictitating membranes):
0: No swelling
1: Any swelling above normal (includes nictitating membranes)
2: Obvious swelling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids more than half closed

Discharge:
0: No discharge (may include small amounts observed in inner canthus of normal animals)
1: Any amount different from normal and/or lacrimation
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs (considerable area around the eye)

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Instillation of approximately 58 mg of Magnesium nitrate hexahydrate (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of slight dulling of the normal luster of the cornea and no epithelial damage was observed. The corneal injury resolved within 24 hours. Iridial irritation grade 1 was observed and resolved within 24 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days. There was no evidence of ocular corrosion.
Individual and mean eye irritation scores are specified in the attached table.
Other effects:
Remnants of the test substance were present in the eye on Day 1. No staining of (peri) ocular tissues by the test substance was observed.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
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 labelling requirement for eye irritation according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

Acute eye irritation/corrosion study with Magnesium nitrate hexahydrate in the rabbit according to OECD 405 guideline and GLP principles.

Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of slight dulling of the normal luster of the cornea and no epithelial damage was observed. The corneal injury resolved within 24 hours. Iridial irritation grade 1 was observed and resolved within 24 hours.

The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days.

Remnants of the test substance were present in the eye on Day 1. No staining of (peri) ocular tissues by the test substance was observed.

Based on these results Magnesium nitrate hexahydrate does not have to be classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

No reliable studies with magnesium nitrate itself are present for skin irritation. However, in a reliable skin irritation study in rabbits (performed comparable to OECD 404) with ammonium nitrate, no signs of skin irritation was observed up to 72 hours.

An acute eye irritation/corrosion study with Magnesium nitrate hexahydrate in the rabbit was performed according to OECD 405 guideline and GLP principles. Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of slight dulling of the normal luster of the cornea and no epithelial damage was observed. The corneal injury resolved within 24 hours. Iridial irritation grade 1 was observed and resolved within 24 hours.

The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days.

Remnants of the test substance were present in the eye on Day 1. No staining of (peri) ocular tissues by the test substance was observed.

Based on these results, magnesium nitrate does not have to be classified for eye irritating properties.

Justification for selection of skin irritation / corrosion endpoint:

One in vivo study on the read-across substance Ammonium nitrate is available. The study has been performed according to OECD and/or EC guidelines. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Justification for selection of eye irritation endpoint:

One in vivo study on magnesium nitrate is available.

Justification for classification or non-classification

Justification for classification or non classification (magnesium nitrate)

With regard to skin and eye irritation magnesium nitrate does not have to be classified according to the CLP Regulation.

Justification for classification or non classification (aqueous solution)

The current harmonized classification of nitric acid (Index No. 007-004-00-1) for the endpoints skin and eye irritation/corrosion is as follows:

Skin Corr. 1A; H314: C ≥ 20%

Skin Corr. 1B; H314: 5% ≤ C < 20%

 

This product is therefore classified as follows:

When the product contains ≥3% calcium nitrate: Eye Damage 1; H318

When the product contains ≥1 - <3% calcium nitrate: Eye Irritant 2; H319

When the product contains <1% calcium nitrate: No Hazard category