Manganese carbonate

Endpoint summary

Description of key information

ORAL
LD50 > 2000 mg/kg, OECD 420, EU Method B.1 bis, Pooles (2009) MnCO3
INHALATION
LC50 > 5.34 mg/L, OECD 403, EU Method B.2, Griffiths (2010) MnO
DERMAL
No study conducted - testing by the dermal route is not considered to be appropriate for this substance

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

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

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

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.

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.

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

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

  

 

 

 

 

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study was conducted under GLP conditions and in accordance with standardised guidelines. The study was therefore assigned a reliability score of 1 in line with the criteria of Klimisch (1997). The overall quality of the database is therefore considered to be high.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 December 2009 to 5 January 2010

Reliability:

2 (reliable with restrictions)

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. Use of data on MnO to address data requirements of MnCO3 is considered to be justified on the basis that manganese is in the same oxidation state in both substances, the anions in both substances are not regarded as toxic, there was a similar level of metal release in bioaccessability studies in artificial lung fluid indicating a similar level of bioavailability of manganese for both substances, and both substances were found to exert no toxicity when dosed at the maximum permissible level in acute oral toxicity studies.

Justification for type of information:

The data on the read-across substance is considered representative.

Reason / purpose for cross-reference:

other: Target record

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed concentration procedure

Limit test:

yes

Species:

rat

Strain:

other: HsdHan: WIST

Sex:

male/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 varied between 200g to 357g*.
* One male animal was slightly above the weight in the protocol (200g - 350g). This deviation was considered not to affect the purpose or validity of the study.
- Housing: Animals were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes.
- Diet : With the exception of the exposure period, free access to food (Harlan 2014 Rodent Diet, Harlan Laboratories UK Ltd, Oxon, UK) was allowed throughout the study.
- Water: With the exception of the exposure period, free access to mains drinking water was allowed throughout the study.
The diet, drinking water, bedding and chew blocks were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- 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

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Consisted of a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) located adjacent to the exposure chamber
- Exposure chamber volume: The cylinderical exposure chamber had a volume of approximately 30 litres (dimensions: 28 cm diameter x 50 cm high).
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of each animal was exposed to the test atmosphere
- Source and rate of air: The SAG 410 was connected to a meter compressed air supply.
- Method of conditioning air: Homogeneity of the test atmosphere within the chamber was not specfically determined during the study. Chambers of the same design (ADG Developments Lts, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animals breathing zone with a wide variety of test materials (Green J D et al, 1984).
- System of generating particulates/aerosols: A dust atmosphere was produced from the test substance using a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany). A particulate separator was introduced before the aerosol entered the exposure chamber in order to remove large particles and thereby increase the inhalable portion of the generated aerosol.
- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK). This device consisted of six impactor stages (9.0, 6.3, 4.0, 1.7, 0.81 and 0.30 µm cut points) with stainless steel collection substrates and a back up glass fibre filter, housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump. The collection substrates and backup filter were weighed before and after sampling and the weight of test substance, collected at each stage, calulated by difference. The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 9.0, 6.3, 4.0, 1.7, 0.81 and 0.30 µm was calculated.
- Treatment of exhaust air: The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/ humidity meter (Hanna Instruments Ltd, Beds., UK) located in a vacent port in the animals' breathing zone of the chamber and recorded every thirty minutes throughtout the four-hour exposure period. Oxygen levels within the exposure chamber were measured by an electronic oxygen analyser (Servomex (UK) Ltd, Crowborough, East Sussex) located in a vacent port in the animals' breathing zone of the chamber and recorded every thirty minutes throughtout the four-hour exposure period. The test atmosphere was generated to contain at least 19% oxygen.


TEST ATMOSPHERE
- Samples taken from breathing zone: yes. The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used glass fibre filters placed in a filter holder. The holder was temporarily sealed in a vacent port in the exposure chamber in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The resulting values were converted to probits and plotted against Log10 cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the geometric standard deviation was calculated. In addition the proportion (%) of aerosol less than 4µm (considered to be the inhalable fraction) was determined. See table 2.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: During characterisation, a group of two rats (one male, one female) were exposed to an atmosphere of the test substance at a mean achieved atmosphere concentration of 2.11 mg/L for four hours. No significant effects were noted for either animal.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric analysis

Duration of exposure:

4 h

Concentrations:

5.35 mg/L

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Any deaths or evidence of overt toxicity was recorded at each concentration. Indivdual bodyweights were recorded prior to treatment on the day of exposure and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes. At the end of the fourteen day observation period the surviving animals were killed by intravenous overdose of sodium pentobarbitone. All animals, including the one that died during the study, were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macropscopic examination for signs of irritancy or local toxicity.

Statistics:

Data evaluations included the relationship, if any, between the animals' exposure to the test substance and the incidence and severity of all abnormalities including behavioural and clinical observations, necropsy findings, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test substance was made.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.35 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 5.35 mg/L for four hours

Clinical signs:

other: Signs of hunched posture and pilo-erection are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded both during and for a short period after exposure. Generalised fur stai

Body weight:

Individual bodyweights, together with weekly bodyweight changes, are given in table 9.
Variations in bodyweight gain are frequently seen for female animals of this strain and age during this type of study and, in isolation, are considered not to be significant.
All male animals and two females exhibited a bodyweight loss during week 1 but recovered to show normal development during week 2. Normal bodyweight development was noted for all other animals during the course of the study.

Gross pathology:

No macroscopic abnormalities were detected at necropsy.

Other findings:

Nott reported

Table 3. The mortality data were summarised as follows:

Mean Achieved Atmosphere Concentration (mg/L)	Deaths
	Male	Female	Total
5.35	0/5	0/5	0/10

 

Table 4. Exposure Chamber Atmosphere Concentration

Duration of Exposure (minutes)	Net Weight of Sample (mg)	Volume of Air Sampled (L)	Chamber Flow Rate (L/min)	Atmosphere Concentration (mg/L)
2	9.17	2	60	4.59
16	10.18	2	60	5.09
30	13.88	2	60	6.94
46	13.63	2	60	6.82
59	9.06	2	60	4.53
75	7.98	2	60	3.99
90	11.09	2	60	5.55
105	11.51	2	60	5.76
120	9.15	2	60	4.58
135	9.01	2	60	4.51
150	7.16	2	60	3.58
165	12.41	2	60	6.21
181	13.91	2	60	6.96
195	12.77	2	60	6.39
210	10.58	2	60	5.29
225	9.04	2	60	4.52
235	11.21	2	60	5.61

 

Mean achieved atmosphere concentration (mg/L) = 5.35

Standard deviation = 1.05

Test substance used (g)	108
Air Flow (L/min)	60
Total Generation Time (mins)	243
Nominal Concentration (mg/L)	7.40

 

Particle size distribution

 

Table 5. Cascade Impactor Data

Impactor Stage Number	Cut Point (µm)	Amount Collected (mg) per sample number			Mean Amount Collected (mg)
		1	2	3
3	9.0	0.05	0.06	0.00	0.04
4	6.3	0.28	0.30	0.17	0.25
5	4.0	0.81	0.85	0.50	0.72
6	1.7	0.46	0.45	0.32	0.41
7	0.81	0.16	0.19	0.08	0.14
8	0.30	0.01	0.05	0.02	0.03
Back-up filter	< 0.30	0.01	0.02	0.03	0.02
Total Mean Amount of Test Material Collected					1.61

 

Table 6. Calculation

Cut Point (μm)	Log10 Cut Point	Mean Cumulative Amount Less Than Cut Point
		(mg)	%	Probit
9.0	0.954	1.57	97.5	6.96
6.3	0.799	1.32	82.0	5.92
4.0	0.602	0.60	37.3	4.68
1.7	0.230	0.19	11.8	3.82
0.81	-0.092	0.05	3.11	3.14
0.30	-0.523	0.02	1.24	2.76

 

Mortality Data

Mean Achieved Atmosphere concentration (mg/L)	Sex	Deaths During Exposure	Deaths Post Exposure (1 hour)	Deaths During Day of Observation								Total Deaths
				1	2	3	4	5	6	7	8-14
5.35	Male	0	0	0	0	0	0	0	0	0	0	0/10
	Female	0	0	0	0	0	0	0	0	0	0

 

Key To Clinical Observations

Fs = generalised green fur staining by the test material

H = hunched posture

P = pilo-erection

Ri = increased respiratory rate

RI = laboured respiration

Rn= noisy respiration

Sh = stained head

Wf= wet fur

O = no abnormalities detected

 

Table 7. Individual Clinical Observations (Day of Exposure)

Mean achieved atmosphere concentration (mg/L)	Animal number and sex	Hours during exposure			On removal From chamber	One hour post-exposure
		1	2	3
5.35	1 Male	Wf	Wf	Wf	Wf H P Ri Fs
	2 Male	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	3 Male	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	4 Male	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	5 Male	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	6 Female	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	7 Female	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	8  Female	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	9 Female	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs
	10 Female	Wf	Wf	Wf	Wf H P Ri Fs	Wf H P Ri Fs

 

Table 8. Individual Clinical Observation (Recovery Period)

Mean achieved atmosphere concentration (mg/L)	Animal number and sex	Days post exposure
		1	2	3	4	5	6	7	8-14
5.35	1 Male	H P Ri Fs	H Ri	Ri	0	0	0	0	0
	2 Male	H P Ri Rn Fs	H Ri	Ri	0	0	0	0	0
	3 Male	H P Ri Fs	H Ri	Ri	0	0	0	0	0
	4 Male	H P Ri Rn Fs	H Ri	Ri	0	0	0	0	0
	5 Male	H P Ri Fs	H Ri	Ri	0	0	0	0	0
	6 Female	H P Ri Fs	H Ri	Ri	0	0	0	0	0
	7 Female	H P Ri Rn Fs	H Ri	Ri	0	0	0	0	0
	8 Female	H P Ri Rn Fs	H Ri	Ri	0	0	0	0	0
	9 Female	H P Ri Rn Fs	H Ri	Ri	0	0	0	0	0
	10 Female	H P Ri Rn Fs	H Ri	Ri	0	0	0	0	0

 

 

Table 9. Individual Bodyweights

Mean achieved atmosphere concentration (mg/L)	Animal number and sex	Bodyweight (g) on Day			Increment (g) During Week
		0	7	14	1	2
5.35	1 Male	299	276	307	-23	31
	2 Male	311	303	348	-8	45
	3 Male	300	274	317	-26	43
	4 Male	292	261	304	-31	43
	5 Male	292	284	316	-8	32
	6 Female	218	225	237	7	12
	7 Female	220	229	236	9	7
	8 Female	219	208	221	-11	13
	9 Female	219	220	224	1	4
	10 Female	227	224	241	-3	17

 

 

Table 10. Individual Necropsy Findings

Mean Achieved Atmosphere Concentration (mg/L)	Macroscopic Observation	Animal Number and Sex
		1 Male	2 Male	3 Male	4 Male	5 Male	6 Male	7 Male	8 Male	9 Male	10 Male
5.35		N	N	N	N	N	N	N	N	N	N

 

 Table 11. Temperature and Relative Humidity in Exposure Chamber

Time (Minutes)	Chamber Temperature (°C) During Exposure	Chamber Relative Humidity (%) During Exposure
0	20	44
30	20	38
60	20	40
90	20	39
120	20	41
150	20	40
180	20	40
210	20	42
240	20	40

 

Table 12. Air Flow and Oxygen Concentration in Exposure Chamber

Time (Minutes)	Air Flow (L/min) During Exposure	Oxygen Concentration (%) During Exposure
-3	60	-
0	60	20.8
30	60	-
60	60	-
90	60	-
120	60	20.8
150	60	-
180	60	-
210	60	-
240	60	20.8

 

 

 

 

 

 

 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 5.35 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of MnO, in the HsdHan:WIST stain rat, was greater than 5.34 mg/L.

Executive summary:

The acute inhalation toxicity of the test substance was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 403 and EU Method B.2.

During the study, a group of five male and five female rats were exposed to a dust atmosphere of test substance at a concentration of 5.34 mg/L for a period of 4 hours using a nose-only exposure system. The animals were observed for mortality and clinical signs of toxicity both during the exposure period and during the 14 day post-exposure period.

None of the animals died during the study and no signs of toxicity that could be related to treatment with the test substance were observed either during the exposure period or during the post-exposure observation period. The acute inhalation median lethal concentration (4 hr LC50) of MnO, in the HsdHan:WIST stain rat, was therefore determined to be greater than 5.34 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

The study was conducted under GLP conditions and in accordance with standardised guidelines. Since the study was conducted with manganese oxide rather than with the registered substance itself, it was assigned a reliability score of 2 in line with the criteria of Klimisch (1997). The overall quality of the database is considered to be good as use of data on MnO is considered to be suitable for the hazard assessment of MnCO3.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Where used in the toxicological endpoints, the read-across from MnO to MnCO3 is justified on the following grounds: 1. Same oxidation state. 2. Similar solubility in water.3. Anions for both not regarded as toxic. 4. Similar leaching of Mn in bioaccessibility studies in artificial lung fluid. 5. Both non-toxic by acute oral route. 6. Both showed negative results in in vivo skin and eye irritation studies.

Oral

The acute oral toxicity of manganese carbonate 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.

The study was conducted with the registered substance, manganese carbonate, and was assigned a reliability score of 1 in line with the criteria of Klimisch (1997).

Inhalation

The acute inhalation toxicity of manganese oxide was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 403 and EU Method B.2.

During the study, a group of five male and five female rats were exposed to a dust atmosphere of test substance at a concentration of 5.34 mg/L for a period of 4 hours using a nose-only exposure system. The animals were observed for mortality and clinical signs of toxicity both during the exposure period and during the 14 day post-exposure period.

None of the animals died during the study and no signs of toxicity that could be related to treatment with the test substance were observed either during the exposure period or during the post-exposure observation period. The acute inhalation median lethal concentration (4 hr LC50) of MnO, in the HsdHan:WIST stain rat, was therefore determined to be greater than 5.34 mg/L.

Use of data on MnO to address data requirements of MnCO3 is considered to be

justified on the basis that manganese is in the same oxidation state in both substances, the anions in both substances are not regarded as toxic, there was a similar level of metal release in bioaccessability studies in artificial lung fluid indicating a similar level of bioavailability of manganese (in the lung) for both substances, and both substances were found to exert no toxicity when dosed at the maximum permissible level in acute oral toxicity studies (thereby confirming the similarity of the toxicological profile of both substances, related to exposure to Mn²⁺).

Since the study was conducted with the read-across substance, manganese oxide, rather that with the registered substance itself, it has been assigned a reliability score of 2 in line with the criteria of Klimisch (1997).

Dermal

In accordance with Column 2 of REACH Annex VIII, information requirement 8.5.3, acute toxicity testing by the dermal route is not required as it is not considered to be an appropriate route of exposure of the substance. The physiochemical properties of MnCO3 suggest it is unlikely to be absorbed through the skin. It has a poor water solubility and inorganic ions do not pass easily through the dermal barrier. In addition, MnCO3 is not acutely toxic by the oral route and therefore it is highly unlikely that it would be toxic via the dermal route which in general absorbs chemicals to a much lesser degree than the gastrointestinal tract. Therefore, this test is not considered scientifically justified to conduct.

Summary of Acute Toxicity

The LD50 was greater than 2000 mg/kg for the oral route. The acute inhalation result from MnO (> 5000 mg/m3) was also indicative that no classification is justified. No dermal absorption is expected for an inorganic substance.

Justification for selection of acute toxicity – oral endpoint
Only one study is available.

Justification for selection of acute toxicity – inhalation endpoint
Only one study is avaialble.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to acute toxicity, nor dermal toxicity as based on low dermal absorption and absence of oral classifcation.