Registration Dossier

Administrative data

Description of key information

ORAL
LD50 > 2000 mg/kg bw, rat (female), OECD 420, EU Method B.1 bis, Pooles (2009)
DERMAL
LD50 > 2000 mg/kg bw, rat (male/female), EU Method B.3, Ferroatlantica (2003)

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:
20 October 2009 to 17 November 2009
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:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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 - 25 °C
- Humidity (%): 30 - 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 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.
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.

 

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

192

200

8

8

 

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

182

200

204

18

4

3 -0 Female

182

185

204

3

19

3-1 Female

176

182

187

6

5

3-2 Female

186

191

206

5

15

3-3 Female

193

199

213

6

14

 

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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the acute oral LD50 of FeMn Slag 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 under GLP conditions and in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The available study was conducted on the registered substance under GLP conditions, and in accordance with standardised guidelines. The study was thereby assigned a reliability score of 1 in line with the criteria of Klimisch (1997).
The overall quality of the database is high.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 January 2003 to 7 February 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
A non-GLP study performed to a standardised guideline with a sufficient level of detail to assess the quality of the relevant results. Since the study was conducted with silicomanganese slag, rather than with the registered substance itself, it has been assigned a reliability score of 2 in line with the criteria of Klimisch (1997). Use of data generated with silicomanganese slag, to address information requirements of ferromanganese slag, is considered to be justified on the basis of the similar compositions of the two substances. Both substances are UVCB substances, containing metallic oxides; each substance is obtained as a by-product in the manufacture of SiMn and FeMn alloy, respectively.
Qualifier:
according to
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 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 °C



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 MATERIAL
- 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: general condition, external alterations, body weight, organ weights, histopathology
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 test material there was slight hair erection, which disappeared in 1-2 hours. The activity and behaviour were not affected, and at the end of the 14 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 material but these healed by themselves during the first week.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the acute dermal LD50 of SiMn slag was estimated to be greater than 2000 mg/kg in male and female rats.
Executive summary:

The acute dermal toxicity of tSiMn slag was investigated in a study which was conducted in accordance with the standardised guideline EU Method B.3.

Under the conditions of the study the acute dermal median lethal dose (LD50) of the test material in male and female rats was determined to be greater than 2000 mg/kg bw.

Since the study was conducted with silicomanganese slag, rather than with the registered substance itself, it has been assigned a reliability score of 2 in line with the criteria of Klimisch (1997). Use of data generated with silicomanganese slag, to address information requirements of ferromanganese slag, is considered to be justified on the basis of the similar compositions of the two substances. Both substances are UVCB substances, containing metallic oxides; each substance is obtained as a by-product in the manufacture of SiMn and FeMn alloy, respectively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study was performed to a standardised guideline with a sufficient level of detail to assess the quality of the relevant results. Since the study was conducted with silicomanganese slag, rather than with the registered substance itself, it has been assigned a reliability score of 2 in line with the criteria of Klimisch (1997). Use of data generated with silicomanganese slag, to address information requirements of ferromanganese slag, is considered to be justified on the basis of the similar compositions of the two substances. Both substances are UVCB substances, containing metallic oxides; each substance is obtained as a by-product in the manufacture of SiMn and FeMn alloy, respectively.
The overall quality of the database is good.

Additional information

Oral

The acute oral toxicity of the test material 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.

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

 

Inhalation

In accordance with Column 2 of REACH Annex VIII, information requirement 8.5.3, acute toxicity 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 < 3.3 % w/w of particles are less than 100 microns diameter.

 

Dermal

The acute dermal toxicity of SiMn slag was investigated in a study which was conducted in accordance with the standardised guideline EU Method B.3.

Under the conditions of the study the acute dermal median lethal dose (LD50) of the test material in male and female rats was determined to be greater than 2000 mg/kg bw.

Since the study was conducted with silicomanganese slag, rather than with the registered substance itself, it has been assigned a reliability score of 2 in line with the criteria of Klimisch (1997). Use of data generated with silicomanganese slag, to address information requirements of ferromanganese slag, is considered to be justified on the basis of the similar compositions of the two substances. Both substances are UVCB substances, containing metallic oxides; each substance is obtained as a by-product in the manufacture of SiMn and FeMn alloy, respectively.


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

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

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.

In accordance with the criteria for classification as defined in Annex VI, Directive 67/548/EEC (DSD), the substance does not require classification with respect to acute toxicity.