Magnesium oxalate

Endpoint summary

Description of key information

Skin irritation is investigated on the basis of read-across study. In vivo study was performed for investigating eye irritation. No adverse effect is observed for skin or eye irritation/corrosion.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information in a detailed justification report is included as attachment to the same record.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
For the determination of analogue in this read-across approach, the following points have been considered:
- Chemical speciation and valency (common magnesium cation: Mg2+).
- The water solubility, as it provides a first indication of the availability of the metal ion in the different compartments of interest. The most simplistic approach to hazard evaluation is to assume that the specific metal-containing compound to be evaluated shows the same hazards as the most water-soluble compounds.
- In fluids of organisms and in aqueous media, dissociation of magnesium oxalate takes place immediately, resulting in formation of magnesium cations (Mg2+) and oxalate anions. Thus, any ingestion or absorption of magnesium oxalate by living organisms, in case of systemic consideration, will inevitably result of exposure to the dissociation products.
- Magnesium is an abundant mineral naturally present in the body. It is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation (IOM 1997, Rude 2010, Rude 2012). Magnesium is required for the normal functioning of several biochemical and physiological reactions and pay an essential role in the human body (Rude 2012). An adult body contains approximately 25 g magnesium, with 50% to 60% present in the bones and most of the rest in soft tissues (Volpe 2012). Human Recommended Dietary Allowances (RDA) for magnesium is up to 420mg per day (IOM 1997). For the same reasons (involvement in biochemical and physiological functions), magnesium is also naturally present in various organisms of the environment such as fish, crustacea or vegetables. Besides they are identified as food sources of magnesium (US 2012). Consequently, it can be concluded that magnesium is of low (eco)toxicological relevance when ingested and taken up systemically. Thus, any possible toxicological or ecotoxicological effect triggered by magnesium oxalate exposure can be attributed to oxalate anion.
- Counter ions: the assumption that the oxalate ion is responsible for the common property or effect implies that the toxicity or ecotoxicity of the counter ion present in the compound will be largely irrelevant in producing the effects to be assessed.
- Likely common breakdown products via physical and/or biological processes for the targeted substance (magnesium oxalate) and the analogues identified cannot present strong differences since the structures are very simple and very similar (formation of Mg2+ or oxalate ion).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical information is provided in the “source” endpoint. No impurity affecting the classification is reported for the source chemical.
Information on the impurities of the target chemical are detailed in the attached report.

3. ANALOGUE APPROACH JUSTIFICATION
The main hypothesis for the analogue approach are verified. They are presented in the detailed report attached. The experimental data performed on the substance (tests performed in this REACH registration dossier on strontium peroxide) confirms the analogue approach performed (same results on analogues).

4. DATA MATRIX
A data matrix is presented in the detailed report attached.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 60 minutes

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 60 min

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

0

Other effects:

not other effect

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the results, interpreted according to Official Journal of the European Union 2001/59/EC dated August 6th, 2001 and OECD n° 404 April 24th 2002, the test substance “OXALIC ACID DI-HYDRATE” must be considered NOT IRRITANT for the skin. In a read across approach, it can be concluded that magnesium oxalate has to be considered as not irritant to the skin.

Executive summary:

A GLP Laboratory test has been conducted following the OECD Guideline TG 404 for Skin irritation.

On the basis of the results, interpreted according to Regulation CE 1272/2008, the test substance “OXALIC ACID DI-HYDRATE” must be considered NOT IRRITANT for the skin, and consequently, in a read across approach, the targeted substance magnesium oxalate can be considered as not irritant.

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:

September 2018

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

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Bernardy, batch No 1601762
- Expiration date of the lot/batch: 29 September 2019
- Production date: 29 September 2016
- Purity test date: 30 September 2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was used after being reduced in fine powder in the study.

FORM AS APPLIED IN THE TEST
As such.

Species:

rabbit

Strain:

New Zealand White

Remarks:

Female

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: supplied by C.E.G.A.V (La Passerie, F-61350 Saint Martin d’Egrenne).
- Age at study initiation: 10 or 11 weeks old
- Housing: individual box installed in conventional air-conditioned animal husbanding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17°C to 23°C
- Humidity (%): 30% to 70%
- Air changes (per hr): at least ten changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (07.00 to 19.00) and twelve hours darkness

Vehicle:

unchanged (no vehicle)

Remarks:

As recommanded in the OECD Guideline, the other eye remained untreated serving as control.

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g of the test item was instilled, after being reduced in fine powder, into the conjunctival sac of one eye after gently pulling the lower lid away from the eyeball.

VEHICLE
No vehicle used

Observation period (in vivo):

1 hour, 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No washing
- Time after start of exposure: Residual test item requiring a physiological saline rinse off was noted at the reading time 1 hour in all animals.

SCORING SYSTEM:
As recommanded by the OECD Guideline

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

The ocular reactions observed during the study have been slight to moderate and totally reversible:
- at the conjunctivae level: a slight to moderate redness noted 1 hour after the test item instillation in all animal and totally reversible between days 1 and 2. This reaction was associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 1 and 2.
- at the iris level: an injection noted 1 hour after the test item instillation in two animals and totally reversible on day 1.

Animal n° Weiht (kg)	Time after treatment	CONJUCTIVAE		IRIS	CORNEA
		CHEMOSIS (A)	REDNESS (C)	LESION (D)	OPACITY (E)
A7107	24 hours	1	1	0	0
	48 hours	0	0	0	0
	72 hours	0	0	0	0
Start: 2.32	TOTAL	1	1	0	0
End: 2.42	Mean	0.3	0.3	0.0	0.0
A7118	24 hours	0	0	0	0
	48 hours	0	0	0	0
	72 hours	0	0	0	0
Start: 2.19	TOTAL	0	0	0	0
End: 2.28	Mean	0.0	0.0	0.0	0.0
A7119	24 hours	0	0	0	0
	48 hours	0	0	0	0
	72 hours	0	0	0	0
Start: 2.27	TOTAL	0	0	0	0
End: 2.35	Mean	0.0	0.0	0.0	0.0
CLASSIFICATION	According to the calculated means, the test item does not have to be classified

Interpretation of results:

GHS criteria not met

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item Magnesium oxalate does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
No symbol and warning label are required.

Executive summary:

The test item Magnesium oxalate was instilled, as supplied, into the eye of three New Zealand rabbits at the dose of 0.1 g.

The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. Test Guideline No. 405 dated October 9th, 2017.

The ocular reactions observed during the study have been slight to moderate and totally reversible:

- at the conjunctivae level: a slight to moderate redness noted 1 hour after the test item instillation in all animal and totally reversible between days 1 and 2. This reaction was associated with a slight

to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 1 and 2.

- at the iris level: an injection noted 1 hour after the test item instillation in two animals and totally reversible on day 1.

In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item Magnesium oxalate does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

No symbol and warning label are required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

No adverse effect are observed, consequently, no classification is needed.