Manganese carbonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 December 2009 to 6 January 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Manganese carbonate

EC Number:

209-942-9

EC Name:

Manganese carbonate

Cas Number:

598-62-9

Molecular formula:

CH2O3.Mn

IUPAC Name:

manganese(2+) carbonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material: MnCO3
- Substance type: Light Brown powder
- Physical state: Solid
- Impurities (identity and concentrations): Insol HCl - 20 ppm, S- 0.041%
- Composition of test material, percentage of components: Mn - 44.8 %, MnO2 - 0.18%
- Purity test date: 29/09/08
- Lot/batch No.: 08793
- 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. Bicester, Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20 % of the initial/mean bodyweight of any previously dosed animals.
- Fasting period before study: Overnight fasting prior to dosing, and 3 to 4 hours post dosing.
- Housing: Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet : 2014 Teklad Global Rodent diet supplied by Harlan Teklad Blackthorn (Bicester, Oxon, UK) available ad libitum
- Water : Mains tap water available ad libitum
- Acclimation period: A minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): A minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL at the 300 mg/kg dose level, 200 mg/mL at the 2000 mg/kg dose level
- Amount of vehicle (if gavage): 10 mL/kg

Doses:

2,000 mg/kg employed in the main test and 300 and 2,000 mg/kg in the sighting test.

No. of animals per sex per dose:

1 animal in each of the sighting dose levels, and 4 animals in the main test.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed on days 0 and 7. Clinical observations were made at 30 minutes, then 1, 2 and 4 hours post dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
- Necropsy of survivors performed: yes, animals were killed by cervical dislocation at the end of the 14 day observation period
- Other examinations performed: clinical signs, body weight and histopathology

Statistics:

Data evaluations included the relationship (if any were noted) between the animal's exposure to the test substance and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. If possible the signs of evident toxicity were also identified. Evident toxicity is defined as the toxic effects which are of a severity such that administration at the next highest level could result in mortality.

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

Results and discussion

Preliminary study:

At both levels of dosing in the sighting study, all animals showed expected bodyweight gains over the observation period. No signs of systemic toxicity were noted, and at necropsy.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: No signs of toxicity were noted at either 300 or 2000 mg/kg

Mortality:

No mortalities occured during the study.

Clinical signs:

other: No signs of toxicity were noted during the study.

Gross pathology:

No macroscopic abnormalities were recorded at necropsy.

Other findings:

Not reported

Any other information on results incl. tables

Table 2. Individual Clinical Observations and Mortality Data – 2000 mg/kg   

Dose level mg/kg	Animal Number and Sex	Effects noted after dosing				Effects noted during periods after dosing (days)
		1/2	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
	3-1 Female	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
	3-3 Female	0	0	0	0	*	0	0	0	0	0	0	0	0	0	0	0	0	0

* - Due to a technician error day 1 observation not performed

0 – No sign of systemic toxicity

  

Table 3. Individual Bodyweights and Bodyweight Changes -2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweights (g) at Day			Bodyweight Gain (g) During week
		0	7	14	1	2
2000	2-0 Female	169	173	188	4	15
	3-0 Female	147	167	178	20	11
	3-1 Female	147	158	170	11	12
	3-2 Female	170	184	201	14	17
	3-3 Female	166	192	203	26	11

 

Table 4. Individual Necropsy Findings – 2000 mg/kg 

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observation
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 substance in the female Wistar rat was determined to be greater than 2000 mg/kg bw under the conditions of the test.

Executive summary:

The acute oral toxicity of the test substance was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis using the fixed dose method.

In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose. One female was dosed 300 mg/kg test substance, by gavage. The animal survived and no clinical signs were noted, therefore a further single female was dosed at 2000 mg/kg, by gavage. Again the animal survived and no clinical signs were noted and so a further four females were dosed at 2000 mg/kg by gavage.

All of the animals survived the 14 -day observation period. No signs of toxicity were noted during the study and all animals exhibited expected bodyweight gains during the course of the study.

The acute oral median lethal dose (LD50) of the test substance in the female Wistar rat was therefore determined to be greater than 2000 mg/kg bw under the conditions of the test.