Manganese ores, reduced

Endpoint summary

Description of key information

Based on column 1 of Annex VIII, the assessment of the toxicokinetic behaviour of the substance is required to the extent that can be derived from the relevant available information.

Additional information

TEST MATERIAL: Manganese Ores, Reduced, (EC Number 273-748-0, CAS Number 69012-49-3)

 

The test material, Manganese Ores, Reduced, also known as Sinter ore, is an industrial by-product from the manufacture of manganese alloys. Visual assessment of the test material described it as to be composed of large lumps to a fine powder (Butler and O'Connor 2009). XRF analysis of the test material showed it to contain primarily Mn₃O₄ (72.42 %) with a minor phases of Al₂O₃ (8.79%), SiO₂ (6.56%), Fe₂O₃ (9.83%) and smaller proportions ≤1% of other metal oxides (LSM 2010). XRD phase identification further identified the major crystalline phases as manganosite, manganese oxide, Mn₃O₄ and minor phases of manganese silicate (Mn₂SiO₄), Tephroite, manganese iron oxide, Hausmannite and ((Mn,Mg)(Mn₂Fe)₂O₄). However, since the test material is an industrial by-product, the individual proportions of the chemical components will vary depending on its source.

 

Absorption

 

The test material, Manganese Ores, Reduced, has an exceedingly low water solubility of ≤1.0 x 10^-5g/L of manganese in solution at 20.0°C, which is equivalent to ≤2.2 x 10^-5g/L of the test material in solution at 20.0°C based on the manganese content of the test material (Butler and O'Connor 2009). It has a very low solubility in artificial gastric juice (1.9 ± 0.11%) and even lower solubility (0.005 ± 0.0005%) in artificial alveolar fluid (Anderson 2009). The acute oral median lethal dose (LD₅₀) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Pooles 2010). A detailed analysis using particle-size distribution of the test material indicates that it is not considered an inhalation hazard since only over 96% of the test material was greater than 100 µm (Butler and O'Connor 2009). As the test material is virtually insoluble in water coupled with its physical inorganic nature (crystalline solid) means that it is very unlikely to be absorbed through the skin. As such, the test material has an exceedingly low potential for any absorption by oral ingestion, inhalation or dermal absorption.

Two studies (Cooper, 2016, 2019) that investigated the in vivo toxicokinetics of the read-across substances, silicomanganese slag and ferromanganese slag, after oral (gavage) administration, showed no evidence of any significant absorption of the test materials.

Poor oral absorption of the registered substance is also supported by a lack of systemic effects in the prenatal developmental toxicity study in the rat up to the limit dose of 1000 mg/kg bw/day conducted on an analogue substance, FeMn Slag (CAS Number 69012-28-8) (Thacker, 2016).  In the rabbit study conducted on FeMn Slag (Stannard, 2020), concerns over fertility were observed at much lower doses indicating potential absorption, however, the toxicological pathway remains unclear as there were some vehicle related confounding factors in this study as well as species specific nuances which cast doubt on the relevance of this data to other species.  A sign of oral absorption was also indicated in the 13-week NTP study conducted on manganese sulphate monohydrate (NTP, 1993). However, this study was conducted at very high dose levels exceeding limit dose with only limited parameters examined, which supplement a low level of toxicity of the registered substance.

 

Metabolism, Distribution and Excretion

 

Since the test material has an exceedingly low potential for absorption by any route it means that the test material will not be readily bioavailable. Any test material that is ingested orally is likely to pass through the GI tract unchanged and be excreted in the faeces. Any small amount of manganese from the test material that is absorbed by the gut will enter the essential manganese pool along with that which is absorbed from the daily nutritional requirement of manganese. The circulating amount of manganese will be controlled by the normal homeostatic mechanism provided by the liver that controls the manganese balance. Any test material that is inhaled is likely to be cleared from the lungs by the mucocilliary elevator into the GI tract and again excreted unchanged in the faeces.

 

References

 

Anderson, K. A. (2009). Bioaccessibility of manganese from manganese Materials in Gastric and Lung (Alveolar) Biofluids, Oregon State University.

Butler, R. E. and B. O'Connor (2009). Sinter Ore (The Manganese Metal Company/BHP): Determination of Water Solubility and Particle Size Distribution. Project number 2702/0004, Harlan Laboratories Ltd.

Cooper, S. (2016) Silico-Manganese Slag (SiMn slag): toxicity study by oral administration to Sprague-Dawley rats for 13 weeks including proof of absorption analysis. Report No. PIQ0003. Unpublished report.

Cooper, S. (2019). Ferromanganese slag (FeMn slag): Toxicokinetic study by oral gavage administration to Sprague-Dawley rats for 7 weeks. Envigo CRS Ltd., FL12FP, 2019-03-26.

LSM (2010). Certificate of Analysis of Manganese Ores, Reduced. Certificate Number 1002011, LSM.

NTP (1993) NPT TR 428: NTP technical report on the toxicology and carcinogenesis of manganese(II) sulphate monohydrate in F344/N rats and B6C3F1 mice (feed studies). Report No. NIH publication number: 94-3159.

Pooles, A. (2010). Sinter Ore: Acute Oral Toxicity in the Rat - Fixed Dose Method. Project Number 2702/0085, Harlan Laboratories Ltd.

Stannard, D. (2020) Ferromanganese Slag: study for effects on embryo-foetal development in the rabbit by oral gavage administration. Report No. VK72FT. Unpublished report.

Thacker, K. (2016) Ferromanganese Slag: study for effects on embryo-fetal development in the rat by oral gavage administration. Report No. PR23XK. Unpublished report.