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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29-12-2009 to 18-01-2010
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:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes (incl. QA statement)
Test type:
fixed concentration procedure

Test material

Constituent 1
Chemical structure
Reference substance name:
Manganese sulphide
EC Number:
242-599-3
EC Name:
Manganese sulphide
Cas Number:
18820-29-6
Molecular formula:
MnS
IUPAC Name:
sulfanylidenemanganese
Details on test material:
- Name of test material: MnS
- Substance type: Dark green powder
- Physical state: Solid
- Impurities (identity and concentrations): Max: O-tot- 1.25% Other elements - 0.75%
- Composition of test material, percentage of components: Min- Mn:62.50% Max-Mn: 65.00% .Min- S :33.50% Max-S: 36.50%
- Purity test date: 27/06/08
- Lot/batch No.: 827551
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
other: HsdHan: WIST
Sex:
male/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 varied between 200g to 357g*. * One male animal was slightly above the weight in the protocol (200g - 350g). This deviation was considered not to affect the purpose or validity of the study.
- Housing: Animals were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes.
- Diet : With the exception of the exposure period, free access to food (Harlan 2014 Rodent Diet, Harlan Laboratories UK Ltd, Oxon, UK) was allowed throughout the study.
- Water: With the exception of the exposure period, free access to mains drinking water was allowed throughout the study.
The diet, drinking water, bedding and chew blocks were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- 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:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Consisted of a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) located adjacent to the exposure chamber

- Exposure chamber volume: The cylindrical exposure chamber had a volume of approximately 30 litres (dimensions: 28 cm diameter x 50 cm high).

- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of each animal was exposed to the test atmosphere

- Source and rate of air: The SAG 410 was connected to a meter compressed air supply.

- Method of conditioning air: Homogeneity of the test atmosphere within the chamber was not specifically determined during the study. Chambers of the same design (ADG Developments Ltd, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animals breathing zone with a wide variety of test materials (Green J D et al, 1984).

- System of generating particulates/aerosols: A dust atmosphere was produced from the test material using a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany). A particulate separator was introduced before the aerosol entered the exposure chamber in order to remove large particles and thereby increase the inhalable portion of the generated aerosol.

- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK). This device consisted of six impactor stages (9.0, 6.3, 4.0, 1.7, 0.81 and 0.30 µm cut points) with stainless steel collection substrates and a back up glass fibre filter, housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump. The collection substrates and backup filter were weighed before and after sampling and the weight of test material, collected at each stage, calculated by difference. The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 9.0, 6.3, 4.0, 1.7, 0.81 and 0.30 µm was calculated.

- Treatment of exhaust air: The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.

- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/ humidity meter (Hanna Instruments Ltd, Beds., UK) located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period. Oxygen levels within the exposure chamber were measured by an electronic oxygen analyser (Servomex (UK) Ltd, Crowborough, East Sussex) located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period. The test atmosphere was generated to contain at least 19% oxygen.


TEST ATMOSPHERE
- Samples taken from breathing zone: yes. The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used glass fibre filters placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump.



TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The resulting values were converted to probits and plotted against Log10 cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the geometric standard deviation was calculated. In addition the proportion (%) of aerosol less than 4µm (considered to be the inhalable fraction) was determined. See table 2.


Duration of exposure:
4 h
Concentrations:
5.34 mg/L
No. of animals per sex per dose:
5 Male and 5 Female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Any deaths or evidence of overt toxicity was recorded at each concentration. Individual bodyweights were recorded prior to treatment on the day of exposure and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes. At the end of the fourteen day observation period the surviving animals were killed by intravenous overdose of sodium pentobarbitone. All animals, including the one that died during the study, were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, necropsy findings, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.34 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
One day after exposure a single female rat was found end.
Clinical signs:
other: Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection, wet fur and generalised green fur staining by the test material. Surviving animals recovered to appear normal from Day 10 post-exposure. See t
Body weight:
All male animals and two females exhibited a bodyweight loss or reduced bodyweight gain during Week 1 but recovered to show normal development during Week 2. Normal bodyweight development was noted for all other animals the course of the study. See table 6
Gross pathology:
No macroscopic abnormalities were detected amongst animals that survived until Day 14 at necropsy. Abnormally dark lungs were noted in the animal that died during the course of the study at necropsy. See table 7.
Other findings:
Nott reported

Any other information on results incl. tables

Table 3: Mortality Data

Mean Achieved Atmosphere Concentration (mg/L)

Deaths

Male

Female

Total

5.34

0/5

1/5

1/10

 

Key to Clinical Observations

Fs = generalised green fur staining by the test material 

H =hunched posture

P =pilo-erection

Ri =increased respiratory rate

Wf = wet fur

X =animal dead

 

Table 4: Individual Clinical Observations (Days of Exposure)

 

Mean Achieved Atmosphere Concentration (mg/L)

Animal Number and Sex

Hours During Exposure

On Removal From Chamber

One Hour Post-Exposure

1

2

3

 

 

 

 

 

5.34

1 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

2 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

3 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

4 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

5 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

6 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

7 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

8 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

9 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

10 Male

Wf

Wf

Wf

Wf H P Ri Fs

Wf H P Ri Fs

 

Table 5: Individual Clinical Observations (Recovery Period)

 

Mean Achieved Atmosphere Concentration (mg/L)

Animal Number and Sex

Day Post Exposure

1

2

3

4

5

6

7

8-14

 

 

 

       

     

 

 

 

 

 

 

 

 

 

     5.34

1 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

2 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

3 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

4 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

5 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

6 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

7 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

8 Male

X

 

 

 

 

 

 

 

9 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

10 Male

H P Ri Fs

H P Ri Fs

H P Ri

H Ri

Ri

Ri

Ri

RiUntil Day 9

 

Table 6: Individual Bodyweights

 

Mean Achieved Concentration (mg/L)

Animal Number and Sex

Bodyweight (g) on Day:

Increment (g) During Week:

0

7

14

At Death

1

2

 

 

 

     

   5.34

1 Male

333

329

358

 

-4

29

2 Male

305

308

324

 

3

16

3 Male

357

352

389

 

-5

37

4 Male

331

327

355

 

-4

28

5 Male

340

323

365

 

-17

42

6 Male

218

223

233

 

5

10

7 Male

241

246

246

 

5

0

8 Male

221

-

-

206

-

-

9 Male

241

237

243

 

-4

6

10 Male

217

215

215

 

-2

0

 

Table 7: Individual Necropsy Findings:

 

Mean Achieved Concentration (mg/L)

Macroscopic Observations

 Animal Number and Sex

1 Male

2 Male

3 Male

4 Male

5 Male

6 Male

7 Male

8* Male

9 Male

10 Male

 

 5.34

Lungs: Abnormally Dark

 

 

 

 

 

 

 

P

 

 

 

N

N

N

N

N

N

N

 

N

N

P = Finding present

N= No abnormalities detected

* = Animal died during study

Table 8. Temperature and Relative Humidity in Exposure Chamber

 

Time (Minutes)

Chamber Temperature(°c) During Exposure

Chamber Relative Humidity (%) During Exposure

0

21

16

30

21

51

60

21

48

90

21

47

120

22

45

150

21

46

180

21

48

210

21

51

240

21

50

 

Table 9. Air Flow and Oxygen Concentration in Exposure Chamber

 

Time (Minutes)

Air Flow (L/min) During Exposure

Oxygen Concentration(%) During Exposure

-3

35

-

0

35

20.8

30

35

-

60

35

-

90

35

-

120

35

20.8

150

35

-

180

35

-

210

35

-

240

35

20.8

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
MnS is not acutely toxic by inhalation.
Executive summary:

The acute toxicity of the test material via the dermal route was assessed according to OECD Test Guideline 403 and EU Method B.2 and in compliance with GLP using a 4 h nose only exposure.

One day after exposure a single female rat was found end. 

Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection, wet fur and generalised green fur staining by the test material. Surviving animals recovered to appear normal from Day 10 post-exposure.

All male animals and two females exhibited a bodyweight loss or reduced bodyweight gain during Week 1 but recovered to show normal development during Week 2. Normal bodyweight development was noted for all other animals the course of the study.

No macroscopic abnormalities were detected amongst animals that survived until Day 14 at necropsy. Abnormally dark lungs were noted in the animal that died during the course of the study at necropsy.

Under the conditions of the study the acute inhalation LC50 was > 5.34 mg/L.