Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 01 May 2012 and 31 May 2012.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted to GLP and in compliance with agreed protocols, with no deviations from standard test guidelines (OECD 420, EU Method B1 bis) and no methodological deficiencies. This study has been selected as the key study because 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).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

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)
Remarks:
Date of inspection: 19-21 July 2011, Date of signature: 31 August 2011
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Manganese bis(dihydrogen phosphate)
EC Number:
242-520-2
EC Name:
Manganese bis(dihydrogen phosphate)
Cas Number:
18718-07-5
Molecular formula:
H3O4P.1/2Mn MnO8P2 H4MnO8P2
IUPAC Name:
manganese bis(dihydrogen phosphate)
Test material form:
solid: crystalline
Details on test material:
Sponsor's identification: Manganese bis(dihydrogen phosphate)
CAS number: 18718-07-5
EINECS number: 242-520-2
Description: pink crystalline solid
Batch number: MV 500
Purity:
P2O5 48.19%
MnO 21.74%
Date received: 16 April 2012
Expiry date: 08 September 2014
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 Limited, Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).
- Fasting period before study: overnight fast immediately before dosing.
- 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 (2014C Teklad Global Rodent diet supplied by Harlan Teklad, Oxon, UK)
- Water (e.g. ad libitum): 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 per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From: Day 0 to Day 14
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

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 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 mg/kg bw, 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: 1
5000 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 subsequently once 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

Preliminary study:
One animal treated at 300 mg/kg bw No mortality observed. See table for clinical observations of the animal treated with 300 mg/kg.
Individual bodyweights and bodyweight changes are given in Table 2: The animal showed expected gains in bodyweight over the observation period.
Necropsy findings are given in Table 3: No abnormalities were noted at necropsy.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths in the 5 animals tested.
Clinical signs:
Individual clinical observations and mortality data are given in Table 4. No signs of systemic toxicity were noted during the observation period.
Body weight:
Individual bodyweights and bodyweight changes are given in Table 5.
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
Individual necropsy findings are given in Table 6.
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 = No signs of systemic toxicity

* = Due to a technician error 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

161

185

205

24

20

 

 

 

 

 

 

 

 

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

 

 

 

Table 6. 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

156

174

190

18

16

3-0

Female

179

195

204

16

9

3-1

Female

173

198

220

25

22

3-2

Female

175

203

217

28

14

3-3

Female

175

193

211

18

18

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (EU CLP: Unclassified).
This study is considered to be reliable and acceptable for use as a key study in accordance with Regulation (EC) No. 1907/2006 (REACH) and for the purposes of classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).