Registration Dossier

Administrative data

Description of key information

Skin irritation (in vitro, OECD 439, RL1): not irritating

Skin corrosion (in vitro, OECD 431, RL1): not corrosive

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

Eye irritation (RA-A 7757 -87 -1, OECD 405, RL1): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
The study was performed between 26 January 2010 and 28 January 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: SkinEthic HCE model
- Tissue batch number(s): not specified
- Production date: not specified
- Shipping date: not specifed
- Delivery date: 26 January 2010
- Date of initiation of testing: not reported

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 3 min exposure: room temperature, 60 min exposure: 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: For rinsing a wash bottle containing DPBS was used. Rinsing was achieved by filling and emptying each tissue insert with a constant soft stream of DPBS for approximately 40 seconds to gently remove any residual test material.
- Observable damage in the tissue due to washing: not reported
- Modifications to validated SOP: none reported

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.5 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: Anthos 2001 microplate reader
- Wavelength: 450 nm
- Filter: not specified
- Filter bandwidth: not specified
- Linear OD range of spectrophotometer: not specified

NUMBER OF REPLICATE TISSUES: 2

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied: 20 mg
- Concentration: moistened with 20 µL sterile distilled water

NEGATIVE CONTROL
- Amount(s) applied: 40 µL

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 40 µL
- Concentration: 8.0N
Duration of treatment / exposure:
3 and 60 minutes
Number of replicates:
2
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 min
Value:
104.7
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60 min
Value:
94.1
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: not reported
- Direct-MTT reduction: no
- Colour interference with MTT: no


ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The mean OD540 of the two negative control tissues were 1.147 for the 3 minute exposure and 1.165 for the 60 minute exposure. The negative control acceptance criterion was therefore satisfied.
- Acceptance criteria met for positive control: The relative mean viability of the positive control material treated tissues was 11.1% after a 3 minute exposure and 5.2% after a 60 minute exposure. The positive control acceptance criterion was therefore satisfied.

Table 1 Mean OD540Values and Percentage Viabilities for the Negative Control Material, Positive Control Material and Test Material:

Material

Exposure Time

Mean OD5401

Relative Mean Viability
(%)

Negative Control

3 minute

1.147

100*

60 minute

1.165

100*

Positive Control

3 minute

0.127

11.1

60 minute

0.061

5.2

Test Material

3 minute

1.201

104.7

60 minute

1.096

94.1


1=     Mean of SkinEthic tissues tested in duplicate

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

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was considered not to have the potential to be corrosive in vivo. Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
In accordance with the testing strategy detailed in Annex VIII, column 1 of Regulation (EC) No. 1907/2006 the assessment of the endpoint ‘skin irritation or skin corrosion’ has been performed following the consecutive steps detailed in the Regulation. As such an in vitro skin corrosion study has been performed. This study shows that magnesium hydrogenorthophosphate is not corrosive to the skin.
Executive summary:

Introduction: The purpose of this test was to evaluate the corrosivity potential of the test material using the SkinEthic in vitro Reconstituted Human Epidermal (RHE) Model after treatment periods of 3 and 60 minutes. Corrosion is directly related to cytotoxicity in the SkinEthic tissue. Cytotoxicity was determined by the metabolic conversion of the vital dye MTT to formazan by viable cells in the test material treated cultures relative to the negative control. The results were used to make a prediction of the corrosivity potential of the test material. The method was designed to meet the requirements of the following:

OECD Guidelines for the Testing of Chemicals No. 431 “In Vitro Skin Corrosion: Human Skin Model Test” (adopted 2004)

Methods: Duplicate SkinEthic RHE tissues were topically treated with the test material for exposure periods of 3 minutes and 60 minutes.

Duplicate negative control and positive control treated tissues were concurrently exposed for 3 minutes and 60 minutes.

At the end of the exposure period each SkinEthic RHE tissue was rinsed using Dulbecco’s phosphate buffered saline (DPBS) and placed into a ‘holding plate’. They were then transferred to an MTT ‘loading plate’ and incubated (37°C, 5% CO2) for 3 hours. At the end of this time, each SkinEthic RHE tissue was blotted dry and placed into an MTT ‘extraction plate’ to extract the reduced MTT from the tissues.

At the end of the extraction period, the reduced MTT solution was mixed for each SkinEthic RHE tissue and 3 x 200µl samples for each tissue were transferred to the appropriate wells of a 96 well plate. The absorbency at 540nm (OD540) of each well was measured. Data are presented in the form of relative mean viability (MTT reduction in the test material treated tissues relative to negative control tissues) for each of the two exposure times.

Results: The relative mean viability of the test material treated tissues was 104.7% after a 3 minute exposure and 94.1% after a 60 minute exposure.

Quality criteria: The quality criteria required for acceptance of results in the test were satisfied.

Conclusion: The test material was considered not to have the potential to be corrosive in vivo.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 23 February 2010 and 01 March 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
other: EU Guideline Testing of Chemicals B46
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
draft version
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN Model kit
- Tissue batch number(s): not specified
- Production date: not specified
- Shipping date: not specified
- Delivery date: 23 February 2010
- Date of initiation of testing:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
- Temperature of post-treatment incubation: 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: For rinsing a wash bottle containing PBS with Ca++ and Mg++ was used. Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of PBS to gently remove any residual test material.
- Observable damage in the tissue due to washing: not reported
- Modifications to validated SOP: none reported

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: Anthos 2001 microplate reader
- Wavelength: 540 nm
- Filter: no reference filter
- Linear OD range of spectrophotometer: not specified

NUMBER OF REPLICATE TISSUES: 3

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be irritant to skin if the viability after 15 minutes exposure and 42 hours post-exposure is less than or equal to 50%
- The test substance is considered to be irritant to skin if the viability after 15 minutes exposure and 42 hours post-exposure is greater than 50%
- Justification for the selection of the cut-off point(s) if different than recommended in TG 431 and 439:
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied: 10 mg

VEHICLE
none, the epidermis has previously moistened with 5µL sterile distilled water

NEGATIVE CONTROL
- Amount(s) applied: 10 µL PBS

POSITIVE CONTROL
- Amount(s) applied: 10 µL SDS
- Concentration: 5% w/v
Duration of treatment / exposure:
15 minutes
Duration of post-treatment incubation (if applicable):
42 hours
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
15 min
Value:
90.6
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks:
6.4%
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: not reported
- Direct-MTT reduction: no
- Colour interference with MTT: no

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The mean OD540 for the negative control treated tissues was ≥0.6 and the SD value of the percentage viability was ≤20%. The negative control acceptance criterion was therefore satisfied.
- Acceptance criteria met for positive control: The relative mean tissue viability for the positive control treated tissues was ≤40% relative to the negative control treated tissues and the standard deviation value of the percentage viability was ≤20%.  The positive control 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

0.647

0.664

0.017

97.4

100*

2.5

0.664

100.0

0.680

102.4

Positive Control Material

0.060

0.043

0.015

9.0

6.4

2.2

0.035

5.3

0.033

5.0

Test Material

0.599

0.602

0.024

90.2

90.6

3.6

0.580

87.3

0.627

94.4

SD=    Standard deviation

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


Table2 : Qualitative Evaluation of Tissue Viability (MTT uptake visual evaluation)

Material

Tissue 1

Tissue 2

Tissue 3

Negative Control Material

-

-

-

Positive Control Material

++

++

++

Test Material

-

-

-

MTT visual scoring scheme
-          =         blue tissue (viable)
+         =         blue/white tissue (semi-viable)
++       =         tissue is completely white (dead

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was considered to be Non-Irritant (NI). This study is conducted according to an appropriate validated in vitro guideline and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint. In addition, the data is considered to be adequate and reliable for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Magnesium hydrogenorthophosphate is not considered to be classified in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
Executive summary:

Introduction: The purpose of this test was to evaluate the skin irritation potential of the test material using the EPISKINTMreconstituted human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours. The principle of the assay was based on the measurement of cytotoxicity in reconstituted human epidermal cultures following topical exposure to the test material by means of the colourimetric MTT reduction assay. Cell viability is measured by enzymatic reduction of the yellow MTT tetrazolium salt (3 -[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) to a blue formazan salt (within the mitochondria of viable cells) in the test material treated tissues relative to the negative controls. The concentration of the inflammatory mediator IL-1α in the culture medium retained following the 42 hour post-exposure incubation period is also determined for test materials which are found to be borderline non-irritant based upon the MTT reduction endpoint. This complimentary end-point will be used to either confirm a non-irritant result or will be used to override the non-irritant result.

Methods:

Triplicate tissues were treated with the test material for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for approximately 42 hours. At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from beneath each tissue was transferred to pre-labelled micro tubes and stored in a freezer for possible inflammatory mediator determination. After MTT loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues. 

At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 µl samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density was measured at 540 nm.

Data are presented in the form of percentage viability (MTT reduction in the test material treated tissues relative to negative control tissues).

Results: 

The relative mean viability of the test material treated tissues was 90.6% after a 15-minute exposure.

Quality criteria: 

The quality criteria required for acceptance of results in the test were satisfied.

Conclusion:  The test material was considered to be Non-Irritant (NI).

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to read across justificiation in IUCLID chapter 13
Reason / purpose:
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:
It is estimated the magnesium hydrogenorthophosphate does not meet the criteria for classification as irritant according to Regulation (EC) No. 1272/2008 (EU CLP).
Executive summary:

No eye irritation properties are considered from the trimagnesium bis(orthophosphate) study by Harlan, 2012. As explained in the justification for type of information, the differences in molecular structure between the magnesium hydrogenorthophosphate 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

Skin:

Skin corrosion and irritation was evaluated in vitro.

Skin corrosion:

In a GLP compliant in vitro study (Harlan, 2010), the skin corrosion potential of magnesium hydrogenorthophospate trihydrate was evaluated using the SkinEthic RHE model according to OECD Guideline 431. Duplicate SkinEthic RHE tissues were topically treated with the test material for exposure periods of 3 minutes and 60 minutes. Duplicate negative control and positive control treated tissues were concurrently exposed for 3 minutes and 60 minutes. At the end of the exposure period each SkinEthic RHE tissue was rinsed using Dulbecco’s phosphate buffered saline (DPBS) and placed into a ‘holding plate’. They were then transferred to an MTT ‘loading plate’ and incubated (37°C, 5% CO2) for 3 hours. At the end of this time, each SkinEthic RHE tissue was blotted dry and placed into an MTT ‘extraction plate’ to extract the reduced MTT from the tissues. At the end of the extraction period, the reduced MTT solution was mixed for each SkinEthic RHE tissue and 3 x 200µl samples for each tissue were transferred to the appropriate wells of a 96 well plate. The absorbency at 540nm (OD540) of each well was measured. Data are presented in the form of relative mean viability (MTT reduction in the test material treated tissues relative to negative control tissues) for each of the two exposure times.

The relative mean viability of the test material treated tissues was 104.7% after a 3 minute exposure and 94.1% after a 60 minute exposure. The quality criteria required for acceptance of results in the test were satisfied. In conclusion, the test material was considered not to have the potential to be corrosive in vivo.

Skin irritation:

In a GLP compliant in vitro study (Harlan, 2010), the skin irritation potential of magnesium hydrogenorthophospate trihydrate was evaluated using the EpiSkin model according to OECD Guideline 439. T

riplicate tissues were treated with the test material for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for approximately 42 hours. At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from beneath each tissue was transferred to pre-labelled micro tubes and stored in a freezer for possible inflammatory mediator determination. After MTT loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues. 

At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 µl samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density was measured at 540 nm.

Data are presented in the form of percentage viability (MTT reduction in the test material treated tissues relative to negative control tissues).

The relative mean viability of the test material treated tissues was 90.6% after a 15-minute exposure. The quality criteria required for acceptance of results in the test were satisfied. In conclusion, magnesium hydrogenorthophosphate trihydrate was considered to be Non-Irritant (NI).

Eye irritation:

Two studies are availabe with magnesium hydrogenorthophosphate. One in vivo study perfomed in 1971 by Kamienski was disregarded since only 10 mg magnesium phosphate was used. This amount is not sufficient according to the recommended test guideline for eye irritation (100 mg) and might lead to false negative results. Another in vitro study was performed an in vitro test was performed which was similar to OECD 492 (Harlan, 2010). As this guideline is available since 2015 and the test was performed in 2010 a major deficiency is the too short incubation time of 10 minutes instead of 6 hours for solids. Furthermore, 30 mg instead of 50 mg were used for the test. The relative mean viability of the test material treated tissue was 106.4% after a 10-minute exposure which leads to the conclusion that the test material has no irritating potential. Due to this major deficiencies which could also lead to a false negative result this study was disregarded.

Since these studies are not reliable, 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 eye irritation potential is assumed.

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, the trimagenesium bis(orthophosphate) and thus magnesium hydrogenorthophosphate 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

Skin irritation: The data available to assess the skin irritation potential of magnesium hydrogenorthophophasphate concludes that no classification is required according to Regulation (EC) No. 1272/2008 (EU CLP). It is not considered scientifically justified on ethical grounds to repeat in vivo studies for this endpoint as the data provided is sufficient.

Eye irritation: Classification is not proposed on the basis of read-across from an analogue substance (trimagnesium bis(orthophosphate). Furhter in vivo testing is deemed to be scientifically unjustified.

There are no data available (workplace observations or studies) to suggest that magnesium hydrogenorthophosphate is a respiratory irritant.