Registration Dossier

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material : FeMn Slag
- Substance type: Grey/green solid lumps
- Physical state: solid
- Major and minor elements: (Mean) MnO- 34.62 %, SiO2-29.18 %, CaO- 20.95 %, Al2O3- 10.38 %, MgO- 3.41 %, FeO-0.53 %, K2O- 0.57 %, TiO2- 0.24 %
- Purity test date: July 2008
- Storage condition of test material: Room temperature in the dark

Test animals

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

Administration / exposure

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.

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.
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.

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

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

Applicant's summary and conclusion

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.