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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental Starting Date: 03 January 2013. Experimental Completion Date: 06 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Trimagnesium bis(orthophosphate)
EC Number:
231-824-0
EC Name:
Trimagnesium bis(orthophosphate)
Cas Number:
7757-87-1
Molecular formula:
Mg3O8P2
IUPAC Name:
trimagnesium bis(orthophosphate)
Test material form:
solid: particulate/powder

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: ad libitum (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water: ad libitum
- 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

Justification: Rats are the preferred species of choice as historically used for safety evaluation studies and are specified in the appropriate test guidelines. If males are used, adequate justification should be provided.

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 suspension in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend 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. Due to a technician error the Day 8 clinical observation was not performed on the animal treated at a dose level of 300 mg/kg. This deviation was considered not to affect the purpose or integrity of the study.
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
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.

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

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

 

 

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).