Manganese ores, reduced

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:

guideline study

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

Details on test material:

- Name of test material : sinter ore
- Substance type: Dark grey rocks
- Physical state: solid
- Major and minor elements: (Mean) Mn 45.9 %, Fe 4.0 %, SiO2 6.5 %, Al2O3 0.583 %, P 0.020 %, MgO 3.7 %, Cao 15.5 %, S 0.03 %
Trace elements: As 8 ppm, B 585 ppm, Co 60 ppm, Cr 60 ppm, Cu 9 ppm, K2O 733 ppm, Na 0.1 %, Ni 25 ppm, Pb < 5 ppm, SrO 0.02 %, TiO2 270 ppm, Zn 60 ppm.
- Purity test date: September 2007
- 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:

water

Details on oral exposure:

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

Doses:

300 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.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: No signs of toxicity were observed at either dose level

Mortality:

No unscheduled deaths occurred during the course of the study.

Clinical signs:

No systemic signs of toxicity were noted during the study.

Body weight:

All animals exhibited expected bodyweight gains throughout the course of the study.

Gross pathology:

No macroscopic abnormalities were noted at necropsy.

Other findings:

Not reported

Any other information on results incl. tables

 

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	181	195	212	14	17

 

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	159	164	165	5	1
	3-0 Female	160	170	176	10	6
	3-1 Female	197	212	216	15	4
	3-2 Female	190	206	208	16	2
	3-3 Female	160	168	178	8	10

 

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:

other: Not classified in accordance with EU criteria.

Conclusions:

Under the conditions of the test, the acute oral LD50 of sinter ore was estimated to be greater than 2000 mg/kg in female Wistar rats.

Executive summary:

The acute oral toxicity of the test material was investigated in a study which was conducted in accordance with the standardised guidelines OECD 420 and EU Method B.1 Bis, and under GLP conditions.

Under the conditions of the test, the acute oral LD50 of sinter ore was estimated to be greater than 2000 mg/kg in female Wistar rats.