Magnesium dimetaphosphate

Endpoint summary

Description of key information

There is no data regarding acute toxicity via oral or inhalation route available for magnesium dimetaphosphate. Read across data with calcium bis (dihydrogenorthophosphate) CAS 7758 -23 -8 and trimagnesium bis(orthophosphate) CAS 7757 -87 -1 is used and considered reliable.

Oral (OECD420, CAS 7757 -87 -1, RL1), rat LD50 > 2000 mg/kg bw (limit test)

Inhalation (OECD 403, CAS 7758 -23 -8, RL1), rat LC50 > 2.6 mg/L air (limit test)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality.

Clinical signs:

No signs of systemic toxicity were noted during the observation period.

Body weight:

The animals showed expected gains in bodyweight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Table 1. Individual clinical observations and mortality data – 300 mg/kg

 

 

Dose level mg/kg	Animal number and sex	Effects noted after dosing (hours)				Effects noted during periods after doing (days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	X	0	0	0	0	0	0

0 = No signs of systemic toxicity

X= Due to a technician error clinical observation not performed

 

 

Table 2. Individual bodyweight and bodyweight changes– 300 mg/kg bw

 

Dose level mg/kg	Animal number and sex	Bodyweight (g) at day			Bodyweight gain (g) during week
		0	7	14	1	2
300	1-0 Female	186	194	209	8	15

 

 

 

 

 

 

 

 

Table 3. Individual Necropsy Findings – 300 mg/kg

 

Dose level mg/kg	Animal number and sex	Time of death	Macroscopic observations
300	1-0 Female	Killed day 14	No abnormalities detected

 

 

 

 

 

 

 

 

 

Table 4. Individual clinical observations and mortality data.– 2000 mg/kg bw

 

Dose level mg/kg	Animal number and sex	Effects noted after dosing (hours)				Effects noted during periods after doing (days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

  0 = no signs of systemic toxicity

 

 

Table 5. Individual bodyweight and bodyweight changes– 2000 mg/kg bw

 

Dose level mg/kg	Animal number and sex	Bodyweight (g) at day			Bodyweight gain (g) during week
		0	7	14	1	2
2000	2-0 Female	180	194	202	14	8
	3-0 Female	149	177	193	28	16
	3-1 Female	153	173	189	20	16
	3 -2 Female	162	186	202	24	16
	3 -3 Female	159	179	187	20	8

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 6. Individual Necropsy Findings– 2000 mg/kg

 

Dose level mg/kg	Animal number and sex	Time of death	Macroscopic observations
2000	2-0 Female	Killed day 14	No abnormalities detected
	3-0 Female	Killed day 14	No abnormalities detected
	3-1 Female	Killed day 14	No abnormalities detected
	3-2 Female	Killed day 14	No abnormalities detected
	3-3 Female	Killed day 14	No abnormalities detected

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of magnesium dimetaphosphate in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System − Unclassified).

Executive summary:

The LD50 was estimated to be greater than 2000 mg/kg bw 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 a oral LD50.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study from a reference substance similar in structure and intrinsic properties. Read-across is justified based on structural similarities of magnesiumphosphate compounds and their similarities in PC/ECO/TOX properties (refer to read across justification for further details). The selected study is thus sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

see analogue justification attached to chapter 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.6 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

All animals survived the scheduled observation period.

Clinical signs:

other: Slight to moderate ruffled fur was noted in all animals on test day 1, one hour after the end of the exposure and persisted slightly until test day 2 in nine animals. From test day 3 onwards, all animals were free from clinical signs until their scheduled

Body weight:

From test day 1 to test day 2, marginal to slight body weight loss was noted in all animals. Thereafter all animals gained weight until scheduled necropsy.

Gross pathology:

There were no macroscopic findings.

Other findings:

Not applicable.

The nominal aerosol concentration was 7.5 mg/L air.

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 of magnesium dimetaphosphate as obtained in this study was estimated to be greater than 2.6 mg/L air (gravimetrically determined mean aerosol concentration). This was the highest technically achievable test concentration. There was no indication of relevant sex-related differences in toxicity of the test item.

In accordance with Regulation (EC) No. 1272/2008 (EU CLP) magnesium metaphosphate is not considered to be classified as acutely toxic via the inhalation route.

Executive summary:

The LC50 was estimated to be greater than 2.6 mg/L air for magnesium dimetaphosphate as found in the source study performed with calcium bis(dihydrogenorthophosphate). As explained in the justification for type of information, the differences in molecular structure between magnesium dimetaphosphate and calcium bis(dihydrogenorthophosphate) are unlikely to lead to differences in the LC50 for inhalation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 600 mg/m³

Quality of whole database:

The available information comprises an adequate and reliable study from a reference substance similar in structure and intrinsic properties. Read-across is justified based on structural similarities of calcium- and magnesiumphosphate compounds and their similarities in PC/ECO/TOX properties (refer to read across justification for further details). The selected study is thus sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

No study is available with magnesium metaphosphate (CAS 13573 -12 -1). Reliable data is available for trimagnesium bis(orthophosphate) (CAS 7757 -87 -1).

Trimagnesium bis(orthophosphate) and magnesium dimetaphosphate are structurally similar ionic compounds. The differences between the two compounds will not have an impact on any acute toxicity potential and therefore, the result from the acute oral toxicity study can reliably be read across to magnesium dimetaphosphate.

In an acute oral toxicity study (OECD 420, Harlan, 2013), one fasted female Wistar rat was treated with 300 mg/kg bw of trimagnesium bis(orthophosphate) in water by gavage. After no toxicity was oberserved in this animal a further female Wistar rat was treated with 2000 mg/kg bw. Since there was also no toxicity observed further 4 female rats were tested with 2000 mg/kg bw test substance and were observed for 14 days. No animals died and no clinical sings were observed during the observation period. All rats appeared normal at necropsy.

The following LD50 after oral administration of trimagnesium bis(orthophosphate) was determined to be > 2000 mg/kg bw.

 

Inhalation:

No study is available with trimagnesium bis(orthophosphate) (CAS 7757 -87 -1). Reliable data is available for calcium bis(dihydrogenorthophosphate) (CAS 7758 -23 -8).

Calcium bis(dihydrogenorthophosphate) and trimagnesium bis(orthophosphate) are structurally similar ionic compounds with the only differences being that calcium is replaced with magnesium. The phosphate groups are structurally identical between the two compounds and any acute toxicity potential will be the same. Magnesium and calcium are both alkali metals from group 2 and periods 3 and 4 of the periodic table, respectively and have only one oxidation state (+2). Magnesium and calcium are among the most abundant elements and are the important essential nutrients for higher plants, algae, animals and human. Both elements are similar in chemical nature and show the related metabolism and similar environmental behaviour. The differences between the two compounds will not have an impact on any acute toxicity potential and therefore, the result from the acute inhalation toxicity study can reliably be read across to trimagnesium bis(orthophosphate).

In an inhalation toxicity study (according to OECD 403, Harlan, 2010), groups of 11 week old Wistar rats (5/sex) were exposed by inhalation route (nose only) to the test substance as a dust and observed for 14 days. The maximal achievable dose was 2.6 mg/L. The rats were exposed for 4 hours. The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats. All animals survived the scheduled observation period. Slight to moderate ruffled fur was noted in all animals after the end of the exposure and was still present in most animals up to test day 2. Thereafter, all animals were free from clinical signs. Transient body weight loss was noted in all animals from test day 1 to test day 2. Normal body weight development was observed thereafter. No macroscopical findings were present at necropsy.

In conclusion, the LC50 of calcium bis(dihydrogenorthophosphate) and thus of magnesium dimetaphosphate) obtained in this study was estimated to be greater than 2.6 mg/L air (gravimetrically determined mean aerosol concentration). There was no indication of relevant sex-related differences in toxicity of the test item.

 

In conclusion, since trimagnesium bis(orthophosphate) and calcium bis(dihydrogenorthophosphate) are reliable read across substances and no acute oral or inhalation toxicity are observed, magnesium dimetaphosphate is considered to be also not acute toxic via oral and inhalation route.

Justification for classification or non-classification

In accordance with Regulation (EC) No.1272/2008 (EU CLP) magnesium dimetaphosphate is not considered to be classified for acute toxicity via oral or inhalation route. The data provided for this endpoint are considered to be conclusive and no further investigation is required.