Manganese ores, reduced

Endpoint summary

Description of key information

Oral

LD50 > 2000 mg/kg bw, OECD 420, EU Method B.1

Inhalation

No study was conducted to assess the acute toxicity via the inhalation route as a particle size distribution study indicated that the substance is not considered to be an intrinsic inhalation hazard.

Dermal

Due to the inorganic nature and insoluble nature of manganese ores, reduced, it is not likely to be absorbed dermally. In addition the lack of oral toxicity in the acute oral toxicity test supports the argument that acute dermal toxicity is not justified on animal welfare grounds. Therefore in accordance with column 2 of Annex VIII, section 8.5.3, this test is not considered necessary.

Supporting information: LD50 > 2000 mg/kg bw (read-across from silicomanganese slags), EU Method B.3

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:

2009-10-20 to 2009-11-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

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.

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 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

 

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2003-1-24 to 2003-2-7

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP not specified but conducted to acceptable test standard

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

no raw data for each animal

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: males 91.3 -99.7 g/ females 94.0 - 101.8 g
- Housing: polypropylene cages with vents on top, with dimensions 445(w) x 695 (l) x 290(h) allowing 10 animals per cage.
- Diet - ad libitum
- Water - ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3°
- Photoperiod (12hrs dark /12 hrs light):

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal region
- % coverage: >10%
- Type of wrap if used: gauze pad and hypoallergenic medical tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 24 hr


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2ml of substance aqueous suspension
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: performed but no details
- Necropsy of survivors performed: yes
- Other examinations performed: body weight,organ weights, histopathology, other: general condition, external alterations

Statistics:

Not reported

Preliminary study:

A previous study conducted several years earlier gave no mortality at 400 mg/kg and thus the use of 2000 mg/kg for this study.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

Not reported

Body weight:

The rate of body weight increase did not differ significantly from control

Gross pathology:

No apparent macroscopic injuries in any of the observed organs. Colour and consistency were normal.

Other findings:

- Other observations:

General condition: After the administration of the substance there was slight hair erection, which disappeared in 1-2 hrs. The activity and behaviour were not affected, and at the end of the14 days they were normal.

External alterations: No changes were detected in the health status of the conjunctiva and mucous membranes. Initially superficial injuries were observed in the dorsal area that was in contact with the test substance but these were healed by themselves during the first week.

Interpretation of results:

other: Not classified in accordance with EU criteria.

Conclusions:

The acute dermal LD50 of the test material was determined to be in excess of 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the read-across substance, silicomanganese slag, was assessed in a study which was conducted in line with the method outlined in the standardised guideline EU Method B.3.

No mortality was observed in Male/Female Sprague-Dawley Stain rats at concentration of 2000 mg/kg bodyweight. The acute dermal LD50 of the test material was therefore determined to be in excess of 2000 mg/kg bw.

 

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mL/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral Route

The acute oral toxicity of the registered substance was assessed according to OECD Test Guideline 420 and EU Method B.1 bis and in compliance with GLP using a fixed dose procedure. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

No unscheduled deaths occurred during the course of the study. No systemic signs of toxicity were noted during the study and no macroscopic abnormalities were noted at necropsy. All animals exhibited expected bodyweight gains throughout the course of the study. Under the conditions of the study, the acute oral LD50 of the test material was estimated to be > 2 000 mg/kg in female Wistar rats.

 

Inhalation Route

In accordance with Annex VIII, column 2 adaptation, testing by the inhalation route is not appropriate, taking into account the very low level of particles of an inhalable size, based on results of particle size distribution study which indicated < 3.1 % w/w of particles are less than 100 microns diameter. The possibility of exposure to particles of an inhalable size is therefore very low and hence inhalation is not deemed to be the most relevant route of exposure.

 

Dermal Route

Due to the inorganic nature and insoluble nature of manganese ores, reduced, it is not likely to be absorbed dermally. In addition the lack of oral toxicity in the acute oral toxicity test supports the argument that acute dermal toxicity is not justified on animal welfare grounds. Therefore in accordance with column 2 of Annex VIII, section 8.5.3, this test is not considered necessary.

Supporting information: The acute dermal toxicity of the read-across substance, silicomanganese slags, was assessed according to EU Method B.3 using a fixed dose procedure. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997). Read-across from SiMn slag to sinter ore is justified on the basis of similar constituents, very poor water solubility and the similar levels of likely availability as demonstrated in the bioaccessability study. Sinter ore has a lower solubility compared to SiMn slag and a similar level of potential systemic availablity.  

During the study there was no mortality during the study and no apparent macroscopic injuries in any of the observed organs. The rate of body weight increase did not differ significantly from control. After the administration of the substance there was slight hair erection, which disappeared in 1 - 2 hrs. The activity and behaviour were not affected, and at the end of the14 days they were normal. No changes were detected in the health status of the conjunctiva and mucous membranes. Initially superficial injuries were observed in the dorsal area that was in contact with the test substance but these were healed by themselves during the first week.

Under the conditions of the study the LD50 was considered to be > 2 000 mg/kg bw.

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 via the oral or dermal routes.

The lack of intrinsic inhalation hazard due to essentially no dust particles from the substance indicates that there is no justification for acute classification by the inhalation route.