Trimanganese bis(orthophosphate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-11-06 to 2012-12-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001-12-17

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2012-11-30

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimanganese bis(orthophosphate)

EC Number:

237-997-9

EC Name:

Trimanganese bis(orthophosphate)

Cas Number:

14154-09-7

Molecular formula:

Mn3O8P2

IUPAC Name:

trimanganese bis(orthophosphate)

Test material form:

solid: crystalline

Details on test material:

- State of aggregation: pink crystalline solid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 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: 151-167 g
- Fasting period before study: overnight
- Housing: animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

BP

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: Arachis oil BP was used because the test item was considered more suitable for dosing in this vehicle.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw: 1
2000 mg/kg: 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 body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:

There was no mortality. No signs of systemic toxicity were noted during the observation period (Table 1).
The animal showed expected gains in bodyweight over the observation period (Table 2).
No abnormalities were noted at necropsy (Table 3).

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.
Please refer to table 4 in the field "Any other information on results incl. tables" below.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period. Please refer to table 4 in the field "Any other information on results incl. tables" below.

Gross pathology:

No abnormalities were noted at necropsy.
Please refer to table 6 in the field "Any other information on results incl. tables" below.

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 Period After Dosing (Day)
		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

Table 2: Individual Bodyweights and Bodyweight Changes – 300 mg/kg

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	166	198	222	32	24

 

Table 3: 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

Dose Level (mg/kg)	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Day)
		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

Table 5: Individual Bodyweights and Bodyweight Changes – 2000 mg/kg

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	155	176	191	21	15
	3-0 Female	156	181	200	25	19
	3-1 Female	152	173	195	21	22
	3-2 Female	167	194	215	27	21
	3-3 Female	151	174	186	23	12

Table 6: 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:

LD50 (female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following:

 OECD Guideline for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (2001)

 Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method

Following a sighting test using one animal at each dose level of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored over a 14-day observation period. All animals were subjected to gross necropsy.

Mortality.There were no deaths.

Clinical Observations.There were no signs of systemic toxicity.

Body Weight. All animals showed expected gains in body weight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion.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 body weight. The test item does not meet the criteria for classification according to the Globally Harmonised Classification System or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.