Magnesium dimetaphosphate

Endpoint summary

Description of key information

No reliable data is available with magnesium dimetaphosphate. Reliable data for the read across substance trimagnesium bis(orthophosphate)(CAS 7757 -87 -1) are available.

Skin Irritation: not irritating in vitro (RA-A 7757 -87 -1, OECD 439, GLP, RL1)
Eye irritation: not irritating in vivo (RA-A 7757 -87 -1, OECD 405, GLP, RL1)

Respiratory irritation: no study available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to read across justification in IUCLID chapter 13

Reason / purpose for cross-reference:

read-across source

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

15 min

Value:

118.8

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks:

8.6% tissue viability

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system: not specified
- Direct-MTT reduction: no
- Colour interference with MTT: no

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes

The individual and mean OD540 values, standard deviations and tissue viabilities for the test item, negative control item and positive control item are given in Table 1. The mean viability values and standard deviations of the test item and positive control, relative to the negative control are also given in Table 1.The relative mean viability of the test item treated tissues was 118.8% after a 15-minute exposure period.

Quality Criteria

The relative mean tissue viability for the positive control treated tissues was 8.6% relative to the negative control treated tissues and the standard deviation value of the percentage viability was 1.0%. The positive control acceptance criterion was therefore satisfied.

The mean OD540 for the negative control treated tissues was 0.659 and the standard deviation value of the percentage viability was 6.2%. The negative control acceptance criterion was therefore satisfied.

The standard deviation calculated from individual percentage tissue viabilities of the three identically treated tissues was 7.6%. The test item acceptance criterion was therefore satisfied.

Table1 : Mean OD₅₄₀ Values and Percentage Viabilities for the Negative Control Material, Positive Control Material and Test Material

Material	OD540of tissues	Mean OD540of triplicate tissues	±SDof OD540	Relative individual tissue viability (%)	Relative mean viability (%)	± SD of Relative mean viability (%)
Negative Control Material¤	0.666	0.659	0.041	101.1	100*	6.2
	0.696			105.6
	0.615			93.3
Positive Control Material¤	0.059	0.056	0.006	9.0	8.6	1.0
	0.061			9.3
	0.049			7.4
Test Material	0.823	0.783	0.050	124.9	118.8	7.6
	0.727			110.3
	0.799			121.2

SD=    Standard deviation

*=     The mean viability of the negative control tissues is set at 100%

¤ = Control group shared with Harlan Laboratories Ltd, Project numbers 41200853, 41200860, 41200866, 41200871, 41200880, 41200884 and 41201543

Interpretation of results:

GHS criteria not met

Conclusions:

Magnesium dimetaphosphate was considered to be non-irritant.

Executive summary:

No skin irriation potential was considered for magnesium dimetaphosphate as found in the source study performed with trimagnesium bis(orthophosphate). As explained in the justification for type of information, the differences in molecular structure between magnesium dimetaphosphate and trimagnesium bis(orthophosphate) are unlikely to lead to differences in the skin irritation potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to read across justification in IUCLID chapter 13

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Initial pain reaction = 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.
No corneal effects were noted during the test.
Iridial inflammation was noted in both treated eyes one hour after treatment.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Moderate conjunnctival irritation was one in one treated eye and minimal conjunctival irritation was noted in the other treated eye at the 24-hour observation with minimal conjunctival irritation noted in both treated eyes at the 48-hour observation.
Both treated eyes appeared normal by the 72-hour observation.

Other effects:

Bodyweight
Both animals showed expected gain in bodyweight during the study.

Interpretation of Results

The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:

Score for conjunctivae =         (A + B + C) x 2
Score for iris                            =         D x 5
Score for cornea                      =         (E x F) x 5

Using the numerical data obtained a modified version of the system ( Modified Kay and Calandra Interpretation of Eye Irritation Test was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.

If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.

 

Table1               IndividualScores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	72304Male				72338Male
	IPR= 2				IPR = 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0
IRIS
D	1	0	0	0	1	0	0	0
Score (D x 5)	5	0	0	0	5	0	0	0
CONJUNCTIVAE
A = Redness	2	2	1	0	2	2	1	0
B = Chemosis	2	1	1	0	2	2	0	0
C = Discharge	2	0	0	0	2	1	0	0
Score (A + B + C) x 2	12	6	4	0	12	10	2	0
Total Score	17	6	4	0	17	10	2	0

 

IPR=  Initial pain reaction

 

Table 2               Individual Total Scores and Group Mean Scores for Ocular Irritation

 

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
72304 Male	17	6	4	0
72338 Male	17	10	2	0
Group Total	34	16	6	0
Group Mean Score	17.0	8.0	3.0	0.0

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

Magnesium dimetaphosphate did not meet the criteria for classification as irritant according to Regulation (EC) No. 1272/2008 (EU CLP) as observed in this study.

Executive summary:

No eye irritating potential is estimated for magnesium dimetaphosphate as found in the source study performed with trimagnesium bis(orthophosphate). As explained in the justification for type of information, the differences in molecular structure between magnesium dimetaphosphate and trimagnesium bis(orthophosphate) are unlikely to lead to differences in the eye irritation potential.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to read across justification in IUCLID chapter 13

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

in vitro irritation score

Run / experiment:

240 min

Value:

9

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

no indication of irritation

 

Corneal Opacity and Permeability Measurement

Individual and mean corneal opacity measurements and individual and mean corneal permeability measurements are given in Table 1.

Corneal Epithelium Condition

The condition of each cornea post treatment is given in Table 2.

One cornea treated with the test item was clear and two corneas were slightly cloudy post treatment. The corneas treated with the negative control item were clear post treatment. The corneas treated with the positive control item were cloudy post treatment.

 

In Vitro Irritancy Score

 

The results are summarised as follows:

Treatment	In vitroirritancy score
Test item	9.0
Negative control	3.9
Positive control	87.7

 

Criterion for an Acceptable Test

The positive control In Vitro irritancy Score was within the range of 58.8 to 126.1. The positive control acceptance criterion was therefore satisfied.

 

 

 

Table 1. Individual and Mean Corneal Opacity and Permeability Measurements

Treatment	Cornea Number	Opacity				Permeability (OD)		In vitroIrritancy Score
		Pre-Treatment	Post-Treatment	Post-Treatment-Pre‑Treatment	Corrected Value		Corrected Value
Negative Control	1	3	7	4		0.032
	2	4	7	3		0.036
	3	4	7	3		0.036
				3.3*		0.035^		3.9
Positive Control	4	4	107	103	99.7	0.688	0.653
	5	6	66	60	56.7	0.909	0.874
	6	3	76	73	69.7	0.987	0.952
					75.3¤		0.827¤	87.7
Test Material	10	6	11	5	1.7	0.022	0.0
	11	4	19	15	11.7	0.018	0.0
	12	4	21	17	13.7	0.033	0.0
					9.0¤		0.000¤	9.0

 

OD= Optical density                 * = Mean of the post treatment-pre‑treatment values      ^= Mean permeability             

¤ = Mean corrected value

Table 2. Corneal Epithelium Condition

 

Treatment	Cornea Number	Observation
		Immediately after Rinsing
Negative Control	1	clear
	2	clear
	3	clear
Positive Control	4	cloudy
	5	cloudy
	6	cloudy
Test Material	10	clear
	11	Slightly cloudy
	12	Slightly cloudy

 

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of this study, magensium dimetaphosphate is considered to be not corrosive or a severe eye irritant in vitro. Therefore, magnesium dimetaphosphate does not meet the criteria for classification for Severe Eye Damage Category 1 according to Regulation (EC) No 1272/2008 (CLP) or the Globally Harmonized System (GHS).
No conclusion can be made whether the substance is an eye irritant or not.

Executive summary:

No eye damaging potential is estimated for magnesium dimetaphosphate as found in the source study performed with trimagnesium bis(orthophosphate). As explained in the justification for type of information, the differences in molecular structure between magnesium dimetaphosphate and trimagnesium bis(orthophosphate) are unlikely to lead to differences in the eye irritation potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Since no studies regarding skin and eye irritation are available for magnesium dimetaphosphate, data was used from a structural analogue trimagnesium bis(orthophosphate). Due to the similar structure of these two substances (as described in the read across justification) a similar skin and eye irritation potential is assumed.

Skin irritation

Skin irritation was evaluated in vitro and in vivo with the structural analogue trimagnesium bis(orthophosphate).

In a GLP-compliant in vitro study (Harlan, 2012), the skin irritation potential of trimagnesium bis(orthophosphate) was evaluated using the SKINETHIC™ RHE Model according to OECD Guideline 439. Triplicate tissues were treated with 10 mg of the test substance for 15 min, followed by rinsing and a 42 h post-exposure incubation period. Triplicate tissues concurrently treated with 10 µL of Dulbecco’s Phosphate Buffered Saline (DPBS) with Ca++ and Mg++ or Sodium Dodecyl Sulphate (SDS) 5% w/v served as negative and positive controls, respectively. At the end of the exposure period, tissues were rinsed prior to MTT loading. Formazan crystals were extracted from the MTT loaded tissues by acidic isopropanol extraction. The optical density of the extracts was measured at 540 nm. The relative mean viability (MTT reduction to formazan in treated vs. negative control tissues) was calculated as percent mean optical density of the isopropanol extracts from treated tissues relative to the negative control.

The relative mean viability of the test substance-treated tissues was 118.8% of the negative control value, while the relative mean tissue viability of the positive control was 8.6%.

This result is supported by in vivo tests done before GLP and guidelines were available (Stauffer, 1972 and Younnger, 1975).

Therefore, based on the study results, trimagnesium bis(orthophosphate) and thus magnesium dimetaphosphate do not meet the criteria for classification according to Regulation (EC) No 1272/2008 (CLP) or the Globally Harmonized System (GHS), and are thus considered to be not skin irritating.

Eye irritation/corrosion

A Bovine Corneal Opacity and Permeability (BCOP) Assay was conducted with trimagnesium bis(orthophosphate) following OECD Guideline 437 and in accordance with GLP (Harlan, 2012). Three corneas were treated with the test substance at 20% w/v in 0.9% w/v sodium chloride solution for 240 min at 32°C. Two groups of three corneas each treated with 0.9% w/v sodium chloride and 20% w/v imidazole in 0.9% w/v sodium chloride served as negative and positive controls, respectively. Following opacity and permeability measurements, the in vitro irritancy score was calculated.

Two corneas treated with the test item were sligthly cloudy and one was clear post treatment. The corneas treated with the negative control item were clear post treatment. The corneas treated with the positive control item were cloudy post treatment. The in vitro irritancy scores of the test substance-treated, negative and positive control corneas were 9.0, 3.9 and 87.7.

Therefore, the test material does not meet the criteria for classification for Severe Eye Damage Category 1 according to Regulation (EC) No 1272/2008 (CLP) or the Globally Harmonized System (GHS), and is thus considered not to be an ocular corrosive or severe irritant in vitro but no conclusion could be made regarding eye irritating potential.

Trimagnesium bis(orthophosphate) was tested for its irritancy potential to the rabbit eye in a GLP-compliant study conducted according to OECD Guideline 405 (Harlan, 2012). Two New Zealand White rabbits were sequentially tested. In each case, 100 mg of the test material was placed into the conjunctival sac of one eye, the untreated eye serving as control. The treated eyes were not rinsed after exposure, and ocular effects were assessed at 1, 24, 48 and 72 h post-instillation. No corneal effects were noted during the study. Iridial inflammation was noted in both treated eyes one hour after treatment. Moderate conjunctival irritation was noted in both treated eyes one and 24 hours after treatment. Minimal conjunctival irritation noted in both treated eyes at the 48-hour observation. Both treated eyes appeared normal at the 72-hour observation. The test item produced individual scores of 0/0 for corneal opacity, 0/0 for iritis, 1.0/1.0 for conjunctival redness and 0.67/0.67 for chemosis, calculated as the mean scores following gradings at 24, 48 and 72 hour after instillation. Observed effects were fully reversible within the 72 h observation period.

Therefore, trimagnesium bis(orthophsohate) and thus magnesium dimetaphosphate do not fulfill the criteria for classification according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), and are thus considered to be not eye irritating.

Justification for classification or non-classification

No classification is proposed for skin or eye irritancy of magnesium dimetaphosphate in accordance with Regulation (EC) No. 1272/2008 (EU CLP). This conclusion is based on reliable and adequate data from a structrual analogue and as such no further testing is anticipated.