Diiron trimolybdenum dodecaoxide

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

From a project funded by the German Science Foundation (DFG), a series of publications have emerged that investigate the potential usefulness of MoO3-coated surfaces for their antimicrobial properties. These are of interest for MoO3 for two major reasons: (i) the antimicrobial activity is plausibly associated with an acidity originating from MoO3 surfaces through the reaction with water, thus forming molybdic acid and releasing protons locally. (ii) the investigators go to great lengths to characterise different calcination conditions and their effect on crystalline structure of MoO3, the corresponding surface area and the intensity of surface acidity and antimicrobial activity. The analytical, morphological and structural parameters are well investigated and documented in these publications. The implications from these investigations are considered to contribute to the understanding of the mechanism of lung reactions in animals exposed via inhalation to fine MoO3 particulates, and are therefore included in the registration dossier of MoO3 as supportive data.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Enhancement of the antimicrobial properties of orthorhombic molybdenum trioxide by thermal induced fracturing of the hydrates

Author:

Shafaei, S. et al.

Year:

2016

Bibliographic source:

Materials Science and Engineering C 58: 1064–1070

Reference 2

Reference Type:

publication

Title:

The photocatalytic properties of Ti–Mo oxides prepared by a simple sol–gel route

Author:

Gutbrod, K. & Zollfrank, C

Year:

2013

Bibliographic source:

J. Sol-Gel Sci Technol, 66:112–119

Reference 3

Reference Type:

publication

Title:

Polymorphs of molybdenum trioxide as innovative antimicrobial materials

Author:

Shafaei, S. et al.

Year:

2013

Bibliographic source:

Surface Innovations 1: 202-208

Reference 4

Reference Type:

publication

Title:

Antimicrobial activity of transition metal acid MoO3 prevents microbial growth on material surfaces

Author:

Zollfrank, C. et al.

Year:

2012

Bibliographic source:

Materials Science and Engineering C 32: 47–54

Reference 5

Reference Type:

publication

Title:

Anodic TiO2 nanotube layers electrochemically filled with MoO3 and their antimicrobial properties

Author:

Lorenz, K. et al.

Year:

2011

Bibliographic source:

Biointerphases 6 (1): 16-21

Materials and methods

Principles of method if other than guideline:

Molybdenum trioxide particles, either embedded in polyurethane or deposited on titanium surfaces, have shown highly promising antimicrobial properties. The results support the proposed antimicrobial mechanism for transition metal oxides such as molybdenum trioxide, based on a local acidity increase as a consequence of the augmented specific surface area.

Investigation of surface acidity of MoO3:

Shafaei, S. et al. (2016):
The investigators subjected MoO3 to various calcination conditions, thereby concluding that an increase in the specific surface area is observed, which is due to crack formation and to the loss of the hydrate water, being at a maximum after calcination at 300 °C. The optimal antimicrobial activity of the material produced under these conditions is considered to be based on a local acidity increase as a consequence of the augmented specific surface area.
The phase transitions over a temperature range up to 600 °C was followed by simultaneous heating and high temperature X-ray diffraction analysis (HT-XRD); scattered intensities were detected by a silicon strip detector. The crystalline phase transition temperatures and water content were measured by differential scanning calorimetry and differential thermal gravimetry.

Gutbrod, K. & Zollfrank, C. (2013):
Mixed titanium and molybdenum oxide powders at different ratios were prepared by sol–gel processing, and then dried/calcined at 300, 500 and 700 °C. Depending on the Ti/Mo ratio and the calcination temperature, either Ti-doped MoO3, mixed oxides (TiO2/MoO3) or Mo-doped TiO2 were formed.

Shafaei, S. et al. (2013):
In this study, the effect of different morphologies of MoO3 on its surface antimicicrobial activities was investigated. According to the authors, several previous investigations had indicated that this property is related to the formation of an acidic surface layer on molybdenum trioxide particles which deteriorates cell growth and proliferation (Zollfrank et al., 2012; Guggenbichler et al., 2010; Tetault et al., 2012; Lackner et al. 2013). The individual crystal phases were characterised by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM).
Molybdenum trioxide dihydrate (99% MoO3) and hexagonal molybdenum trioxide (70 wt% MoO3 × 0·33 NH3 × 0·34 H2O) with different crystalline structures were synthesized, and their antimicrobial activity dependant on the temperature of calcination (200, 300 and 700°C) was investigated.

Zollfrank, C. et al. (2012):
This publication reports on the antimicrobial properties of molybdic acid (H2MoO4) formed on the surface of molybdenum trioxide (MoO3) particles. In this case, a sample rod was used i.e. their 300 heat treated MoO3 was mixed with polymer (acrylic resin) and then made into rods. MoO3 has an acidic reaction but, the dispersion of heat treated MoO3 is thought to have an enhanced acidity and it is the increase which leads to the antibacterial effect. The antimicrobial activity is based on the formation of an acidic surface, thereby inhibiting cell growth and proliferation. The acidic surface reaction (release of hydroxonium ions) can be described by the following formulae:

MoO3 + H2O ⇄ H2MoO4 and H2MoO4 + 2 H2O ⇄ 2 H3O+ + MoO42−

First, molybdic acid is formed on the surface of MoO3; hydroxonium ions (H3O+) will then be released from H2MoO4 in the presence of water, thereby releasing molybdate ions (MoO42−). In the equilibrium state, the molybdates will be retransformed into molybdic acid H2MoO4.

Lorenz, K. et al. (2011):
Similar to other efforts investigating the antimicrobial activity of MoO3 surfaces, the authors in this case studied the antimicrobial efficiency of TiO2 nanotubes filled with MoO3 annealed at 300 and 450°C. The morphology of the particles was assessed by field-emission scanning electron microscopy and X-ray diffraction; chemical composition was verified with the aid of x-ray photoelectron spectroscopy (XPS).

Type of method:

in vitro

Endpoint addressed:

carcinogenicity

other: surface acidity

Test material

Test material information

Constituent 1

Reference substance name:

Molybdenum trioxide

EC Number:

215-204-7

EC Name:

Molybdenum trioxide

Cas Number:

1313-27-5

Molecular formula:

MoO3

IUPAC Name:

molybdenum trioxide

Results and discussion

Details on results:

Shafaei, S. et al. (2016):
During the decomposition of the dihydrate to the monohydrate, the size of the particles decreases: micrographs of MoO3 calcined at 300°C show a series of parallel cracks, whereas material calcined at 600°C consolidates and the particle sizes increases again. Freshly prepared MoO3×2H2O had a specific surface area of 2.5 m2/g, MoO3 treated at 100, 300 and 600 degrees C exhibited specific surface areas of 8.4 m²/g, 50.7 m²/g and 0.7 m²/g, respectively.
The MoO3 with the highest antimicrobial activity was the sample treated at 300 °C. The antimicrobial properties were investigated using S. aureus ATCC 25923 (MRSA), E. coli ATCC 27020 and P. aeruginosa ATCC 10145 using the roll-on test as described in Zollfrank et al (2012). In brief, a sample rod with the respective molybdenum samples is incubated in an inoculum with reference bacteria of 107–109 CFU/mL for 4 h. The authors state that this supports the proposed mechanism for elimination of bacteria due to the formation of an acidic environment. The antibacterial properties are due to a particular form of MoO3 created in the preparation of the materials. The surface pH value on the particles is locally decreased below 5.5 as a consequence of proton release from molybdic acid HMoO4, which is formed from MoO3 in the presence of humidity (Lorenz et al. 2011; Gutbrod et al. 2013; Zollfrank et al. 2012).
It was found in an earlier study that a high specific surface area alone is not sufficient to attain a high antimicrobial activity (Shafaei et al. 2013). The combination of a considerable proton release rate and a large specific surface area is required to achieve the efficient antibacterial properties […] hydration of free surfaces, which would indicate the accessibility of the entire surface. .
the authors assume that the antibacterial property is due to increased acidity but provide no direct evidence for this e.g. from pH of materials in contact with water or spectroscopic measurements. The initial observations appear to be in a series of patents (Guggenbichler et al., 2011).
In catalysis it is well known that acidity is enhanced for MoO3 supported on oxides such as SiO2 and e.g. this is circumstantial evidence for generally increased acidity of MoO3 on titania e.g. Chandra et al. (2014): “The presence of Lewis and Bronsted acidic sites was determined by the FTIR of adsorption of pyridine. When pyridine was adsorbed on the MoO3 /SiO2 samples, the adsorption bands for either the Lewis or Bronsted acidity were not found. This indicates that either very weak or no acidity is present on the sample. Furthermore, MoO3 /TiO2 showed bands around 1447 cm-1 due to Lewis acid sites; a peak at 1540 cm-1 confirmed the presence of Bronsted acidity. MoO3 /ZrO2 also showed the presence of Lewis and Bronsted acidic sites”.

Gutbrod, K. & Zollfrank, C. (2013):
These products were characterised by scanning electron microscopy with attached X-ray dispersive energy analysis, X-ray diffractometry, Raman spectroscopy, gas adsorption and optical characterisation by ultraviolet/visible spectroscopy (for the analysis of photocatalytic properties by decolourisation of methylene blue solutions under visible light irradiation). The phase composition, the specific surface and the photocatalytic activity were influenced by the molybdenum content and the calcination temperature. Optimal photocatalytic properties were observed for Ti-doped MoO3. As in another publication (Shafei et al., 2016), the surface area for 7 different mixture ratios (Ti(Mo) was consistently highest in material calcined at 300°C.

Shafaei, S. et al. (2013):
Material calcined at 300°C showed a needle-fractured orthorhombic polymorph appearance. According to the authors, such layered structures in different directions are seldomly found, but are assumed to exhibit a high potential to produce an acidic surface and antibacterial activity due to a possible interaction with water molecules. The antimicrobial effectiveness of transition metal oxides such as molybdenum oxides are therefore related to an acidic surface reaction. The investigation of antimicrobial activity with different bacterial pathogens indicated a superior efficacy of calcined molybdenum oxide orthorhombic and monoclinic phases compared to commercially available orthorhombic MoO3.

Zollfrank, C. et al. (2012):
Acidic surfaces are known to inhibit bacterial and fungal growth (such as staphylococci, streptococci, enterococci, legionellae, lactobacilli, and Candida or Aspergillus spp.) and effectively kill microorganisms at pH values of 3.5–4.0; gram-negative microorganisms are growth inhibited even killed at somewhat higher pH values (up to 5.5).
MoO3 dispersed in the lung is like MoO3 dispersed in the polymer. The antibacterial effect is due not to MoO3 per se but a particular composite. MoO3 by itself e.g. in water is not antibacterial.

Lorenz, K. et al. (2011):
The author report that “[…] the heat treatment is the key factor for establishing significant antibacterial properties. A marked effect occurs only for molybdenum oxide phases present as crystalline MoO3 phase after annealing at 300 and 450 °C. An antimicrobial activity of a MoO3 particle suspension in water could not be confirmed. It was shown that MoO3 up to a concentration of 1 g/l had no effect on cell counts of Acinetobacter sp. and several other bacteria. These results support a contact-based antibacterial effect, which is related to a local change in the pH value, and the low cytotoxicity of the material. The local increase in the amount of H3O+ ions in the opening area of the nanotubes reduces the pH value on the substrate surface even if there is no molybdenum oxide present directly at the surface.” The effect is a property of MoO3 in a particular environment on a surface and not MoO3 as such.

References:
- Chandra, P.; Doke, D. ; Umbarkar, S. and Biradar, A. (2014): One-pot synthesis of ultrasmall MoO3 nanoparticles supported on SiO2 , TiO2 , and Zr2 nanospheres: an efficient epoxidation catalyst. J.Mater.Chem.A , 2 , 19060 – 19066.
- Guggenbichler, J. P.; Eberhardt, N.; Martinez, H. P.; Wildner, H. Substance With an Antimicrobial Effect. US 57199 A1, Mar. 2010.
- Guggenbichler et al. (2011): United States Patent Application Publication Pub. No.: US 2011/0186281 A1 Pub. Date: Aug. 4, 2011 (54) COOLING TOWER HAVING REDUCED MICROBIAL CONTAMINATION.
- Lackner, M.; Maninger, S.; Guggenbichler, J. P. Saure Oberflächen als neuartige Kontaktbiozide. Nachrichten aus der Chemie 2013, 61, 112–115.
- Tétault, N.; Gbaguidi-Haore, H.; Bertrand, X.; Quentin, R.; Van der Mee-Marquet, N. Biocidal activity of metalloacid-coated surfaces against multidrug-resistant microorganisms. Antimicrobial Resistance and Infection Control 2012, 1, 35–42.

Applicant's summary and conclusion

Conclusions:

We conclude that the antimicrobial acidity effect of MoO3 is specific to the particular preparations and is not a general property of MoO3. The situation of MoO3 is the lung may be similar i.e. a surface effect so we cannot generalise from the NTP study even if we attribute the apparent carcinogenicity to MoO3.