Registration Dossier

Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
10 December 2008 to 1 December 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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.

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Eleven materials were analysed for bioaccessibility of manganese in gastric and lung (alveolar) biofluids. Samples were extracted by artificial gastric and artificial alveolar (lung) fluids according to the physiological parameters defined by Stopford et al (2003) and analysed for manganese. This method is based on ASTM D5517-07 standard method for determining extractability of metals from art material. Standard analytical methods were created and method validation packages were developed, and completed, for the artificial biofluids methods as designated by the FSES Laboratory Quality Assurance Program Plan.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material : Silicomanganese slag, Manganese, Manganese (II, III) oxide, Manganese (IV) oxide, Manganese (II) carbonate, Manganese(II) oxide, Ferromanganese slag, Manganese (II) sulphide, Ferromanganese and Sinter ore
- Molecular formula : SiMn, Mn, Mn3O4, MnO2, MnCO3, MnO, FeMn, MnS, HC FeMn, Sinter ore
- Physical state: See table 1
- Lot/batch No.: See table 1
- Storage condition of test material: Room temperature
- Other: A total of 24 manganese materials were received between 10 December 2008 and 7 October 2009 from Harlan Ltd or directly from the supplier through international mail carrier. The samples arrived at room temperature in either amber jars, plastic bags or plastic containers as variable sized particles. Eleven samples were extracted and analysed upon authorisation once they were received in a form that could be inhaled or orally digested(Table 1).

Results and discussion

Any other information on results incl. tables

For each batch, the calibration curves using 5 or more standards had r² values greater than 0.97.Over-spikes recoveries ranged from 89 to 108% and all blanks were below method detection limits. The percent recoveries for the over-spikes of the CRM and reagent blank are summarised in Table 2.

Table 2: Quality control results for the manganese material sample batches extracted and analysed according to SAMs 806 and 807

Artificial Gastric

Artificial Alveolar

MDL

0.097

0.053

% Recovery reagent blank (0.5 µg/mL) avg ±SD, n=5

99 ± 5.8

95 ± 4.7

% Recovery CRM (10 µg/mL) avg ±SD, n=5

93 ± 3.7

99 ± 12

% Recovery instrument check standards (10 µg/mL) avg ±SD, n=7

101 ± 3.6

100 ± 3.4

 

Table 3: Maximum extractable manganese level (% of available in the material tested) in manganese metal material determined after applying digestion and inhalation artificial biofluids (SAMs 806 and 807, respectively).

Metal material

% Mn in metal material (average ± standard deviation), n=3

Artificial Gastric

Artificial Alveolar

Mn3O4

13 ± 3.2

0.000047 ± 0.000051

MnO2

0.092 ± 0.016

BDL

MnCO3

16 ± 1.9

0.0013 ± 0.00027

MnO

12 ± 4.4

0.0033 ± 0.0021

MnS

55 ± 0.33

0.011 ± 0.011

SiMn

5.8 ± 0.36

0.019 ± 0.0018

SiMn slag

0.88 ± 0.041

0.0098 ± 0.00057

HC FeMn

7.8 ± 0.093

0.012 ± 0.00065

FeMn slag

24 ± 1.4

0.024 ± 0.0070

Sinter ore

1.9 ± 0.11

0.0054 ± 0.00048

Mn metal

59 ± 2.9

0.020 ± 0.00055

 

 

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study the level of manganese release following a 2 hour exposure of FeMn slag to artificial gastric acid was 24% Mn (± 1.4% SD). The level of manganese release following a 2 hour exposure of FeMn slag to artificial lung fluid was 0.024% Mn (± 0.0070% SD).
Executive summary:

Eleven materials were analysed for bioaccessibility of manganese in artificial gastric and lung (alveolar) biofluids. Samples were extracted from the artificial gastric and artificial alveolar (lung) fluids according to the physiological parameters defined by Stopford et al (2003) and analysed for manganese. This method is based on ASTM D5517-07 standard method for determining extractability of metals from art material. Standard analytical methods were created and methods validation packets were developed and completed for the artificial biofluids methods as designated by the FSES Laboratory Quality Assurance Program Plan.

All concentrations of manganese in the extract were above detection limit except for MnO2 exposed to the alveolar fluid. In general, the maximum extractable manganese levels in the gastric solution were the manganese metals and the MnS in the gastric solution. The least extractable manganese material is the MnO2 in both the gastric and alveolar biofluids. In the gastric biofluids, the average dissolution of manganese in the SiMn and HC FeMn alloys were approximately similar, while the manganese in the SiMn slag was substantially less and the FeMn slag was approximately 3 times greater than the corresponding alloys. The dissolution of manganese in the artificial alveolar fluid was very low for all materials, with the amount of manganese measured in the gastric solution an order of magnitude or greater.

Under the conditions of the study the level of manganese release following a 2 hour exposure of FeMn slag to artificial gastric acid was 24% Mn (± 1.4% SD). The level of manganese release following a 2 hour exposure of FeMn slag to artificial lung fluid was 0.024% Mn (± 0.0070% SD).