Magnesium bis(dihydrogenorthophosphate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 19 November 2012 and 20 December 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 10 July 2012, Date of signature: 30 November 2012

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium bis(dihydrogenorthophosphate)

EC Number:

236-004-6

EC Name:

Magnesium bis(dihydrogenorthophosphate)

Cas Number:

13092-66-5

Molecular formula:

H3O4P.1/2Mg

IUPAC Name:

magnesium bis(dihydrogenorthophosphate)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Sponsor's identification: IP 31: Magnesium bis(dihydrogenorthophosphate)
EC number: 236-004-6
CAS number: 13092-66-5
Description: white powder
Batch number: Laboratory preparation 11.10.11
Purity: >98%
Date received: 02 October 2012
Expiry date: not supplied
Storage conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ±20% of the bodyweight of the initially dosed animal.
- Fasting period before study: overnight fast
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum(2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30 - 70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

For the purpose of the study the test item was freshly prepared, as required, as a solution or suspension in distilled water.
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw: 1
2000 mg/kg bw: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality.

Clinical signs:

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

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

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	0	0	0	0	0	0	0

0 = No signs of systemic toxicity

 

 

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	156	178	191	22	13

 

 

 

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	146	169	185	23	16
	3-0 Female	171	199	222	28	23
	3-1 Female	165	185	206	20	21
	3-2 Female	160	189	204	29	15
	3-3 Female	161	181	202	20	21

 

 

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

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System − Unclassified).
The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008 (EU CLP), relating to the Classification, Labelling and Packaging of Substances and Mixtures.

This study has been selected as the key study because the study is considered to be adequate and reliable for use as a key study in accordance with Regulation (EC) No. 1907/2006 (REACH). In addition, the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).