Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-10-20 to 2009-11-25
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 guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Manganese oxide
EC Number:
215-695-8
EC Name:
Manganese oxide
Cas Number:
1344-43-0
Molecular formula:
MnO
IUPAC Name:
manganese oxide
Details on test material:
- Name of test material: MnO
- Substance type: Green powder
- Physical state: Solid
- Impurities (identity and concentrations): MnO2 0.46 %, Fe 56 ppm, Ins. ac. 15 %, H2O at 105 °C 0.01 %
- Composition of test material, percentage of components: Mn 77.8 %
- Purity test date: 29/09/08
- Lot/batch No.: 104833-06
- 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:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL at the 300 mg/kg dose level, 200 mg/mL at the 2000 mg/kg dose level
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Polyethylene glycol 400 was selected as the the vehicle as the test material did not dissolve/suspend in distilled water, arachis oil BP or dimethyl sulphoxide.
Doses:
2,000 mg/kg employed in the main test and 300 and 2,000 mg/kg in the sighting 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 noted at either 300 or 2000 mg/kg
Mortality:
No mortalities occurred during the study.
Clinical signs:
No signs of toxicity were noted during the study.
Body weight:
All animals exhibited expected bodyweight gains during the course of the study.
Gross pathology:
No macroscopic abnormalities were recorded 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

159

171

186

12

15

 

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

180

191

202

11

11

3-0 Female

178

190

195

12

5

3-1 Female

188

199

206

11

7

3-2 Female

171

184

186

13

2

3-3 Female

166

181

189

15

8

 

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 the female Wistar rat was determined to be greater than 2000 mg/kg bw under the conditions of the test.

Categories Display