Magnesium diethyl dicarbonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-06 to 2010-04-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conduced according to guidelines in a GLP-certified laboratory.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2000); including the most recent partial revisions.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium hydroxide

EC Number:

215-170-3

EC Name:

Magnesium hydroxide

Cas Number:

1309-42-8

Molecular formula:

H2MgO2

IUPAC Name:

magnesium dihydroxide

Details on test material:

Identification: Magnesium hydroxide
Molecular formula: Mg (OH) 2
Molecular weight: 58.32
Stability under storage conditions: Stable
Description: White powder
Test substance storage: At room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan, Belton, Leics, England
- 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: Animals were individually housed in labelled cages with perforated floors and shelters.
- Diet: Pelleted diet for rabbits approximately 100 grams per day was provided at least three times a week.
- Water: Free access to tap water
- Acclimation period: Acclimitisation period was at least 5 days before start of treatment under laboratory conditions.
Results of analysis for diet, hay and water were assessed and did not reveal any findings that were considered to have affected the study integrity.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0±3.0°C
- Humidity (%): 40-70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 06-04-2010 to: 2-04-2010

Test system:

Amount/ concentration applied:
Animals were treated by instillation of on average, 57.3 mg (range 57.0-57.5 mg) of the test substance (a volume of approximately 0.1mL) in the conjunctival sac of one of the eyes.

Observation period:
Observations were made 1, 24, 48 and 72 hours after instillation.
Mortality/ Viability: Twice daily
Toxicity: At least once daily
Body weight: Day of treatment and after the final observation
Necropsy: No necropsy was performed according to protocol.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

57.3 mg (range 57.0-57.5 mg)

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.

Number of animals or in vitro replicates:

3 males were used in the treatment.

Details on study design:

The study was performed in a stepwise manner and was started by treatment of a single rabbit. The other two animals were treated in a similar manner 2 weeks later, after considering the degree of eye irritation observed in the first animal.
Washing: Immediately after the 24-hour observation period, a solution of 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. The procedure was repeated to assess recovery. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no irritation

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no irritation

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no irritation

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no irritation

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no irritation

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no irritation

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 72 hours in all animals.

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 72 hours in all animals.

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 72 hours in all animals.

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 72 hours in all animals.

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

0.3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 72 hours in all animals.

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

0.3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 72 hours in all animals.

Irritant / corrosive response data:

Instillation of approximately 57 mg of Magnesium hydroxide into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of a slight dulling of the normal lusture and/or epithelial damage (maximum 10% of the corneal area) in two animals. The corneal injury had resolved within 24 or 48 hours. Iridial irritation grade 1 was observed in all animals and had resolved within 24 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 72 hours in all animals.

Coloration/ Remnants
Remnants of the test substance were present in the eye of two animals on Day 1.

Toxicity/ Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1:

Mean value eye irritation scores

 

	Mean 24, 48 and 72 hours.
Animal	Corneal opacity	Iris	Conjunctivae
			Redness	Chemosis
328	0.0	0.0	1.0	0.0
377	0.0	0.0	1.0	0.3
379	0.0	0.0	1.0	0.3

 

 

Table 2:

Animal specifications

 

Animal	Sex	Age at start (weeks)	Body weights( grams)
			Prior to application	At termination
328	Male	10-12	2198	2256
377	Male	7-9	1516	1701
379	Male	7-9	1615	1739

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on these results Magnesium hydroxide does not have to be classified and has no obligatory labelling requirement for eye irritation according to the:
-Globally Harmonised System of Classification and Labeling of Chemicals (GHS) of the United Nations
-Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.