Manganese

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-10-20 to 2009-11-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted to current accepted guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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

EC Number:

231-105-1

EC Name:

Manganese

Cas Number:

7439-96-5

Molecular formula:

Mn

IUPAC Name:

manganese

Details on test material:

- Name of test material : Mn
- Substance type: grey solid
- Physical state: solid
- Analytical purity: Mn (Met) 99.9 %, metallic manganese calculated excluding non-metallic elements. Mn 99.8 %, total manganese on a total weight basis.
- Impurities (identity and concentrations): sulphur 0.034 %, carbon 0.001 %, hydrogen 0.0007 %, oxygen 0.1 %, nitrogen 0.04 %, iron < 0.001 %, phosphorous 0.001 %, silicon 0.001 %, lead 0.001 %, copper 0.0003 %, vanadium < 0.0001 %.
- Purity test date: 2008/08/04
- 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 (300 mg/kg) and 200 mg/mL (2000 mg/kg).
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

Doses:

300 mg/kg and 2000 mg/kg in the sighting study and 2000 mg/kg in the main 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 material 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, no gross abnormalities were observed.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: No toxicity was observed at 2000 mg/kg

Mortality:

No mortalities were noted at either dose level

Clinical signs:

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

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Not reported

Any other information on results incl. tables

Table 1: Clinical Observations and Mortality Data, Dose Level 300 mg/kg

 

Dose Level mg/kg	Animal No.	Effects Noted After Dosing (Hrs)				Effects Noted Post Dosing (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

 

Table 2: Bodyweight and Bodyweight Changes, Dose Level 300 mg/kg

 

Dose Level mg/kg	Animal No.	Bodyweight (g) on Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	184	198	216	14	18

 

Table 3: Necropsy Findings, Dose level 300 mg/kg

 

Dose Level mg/kg	Animal No.	Time of Death	Macroscopic Observations
300	1-0 Female	Killed Day 14	No abnormalities detected

 

Table 4: Clinical Observations and Mortality Data, Dose Level 2,000 mg/kg

Dose Level mg/kg	Animal No.	Effects Noted After Dosing (Hrs)				Effects Noted Post Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2,000	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 5: Bodyweight and Bodyweight Changes, Dose Level 2,000 mg/kg

 

Dose Level mg/kg	Animal No.	Bodyweight (g) on Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2,000	2-0 Female	170	181	193	11	12
	3-0 Female	195	205	210	10	5
	3-1 Female	194	202	209	8	7
	3-2 Female	195	198	206	3	8
	3-3 Female	161	167	169	6	2

 

Table 6: Necropsy Findings, Dose level 2,000 mg/kg

 

Dose Level mg/kg	Animal No.	Time of Death	Macroscopic Observations
2,000	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:

study cannot be used for classification

Conclusions:

The acute oral median lethal dose (LD50) of the test material in female Wistar rat was found to be greater than 2000 mg/kg bw.