Molybdenum trioxide

Carcinogenicity

Description of key information

 Molybdenum trioxide is classified as carcinogens category 2 according to commission Regulation (EC) No 790/2009, amending Regulation (EC) No 1272/2008. The placing of a substance in Category 2 is done on the basis of evidence in animal studies, but which is not sufficiently convincing to place the substance in Category 1A or 1B.

Key value for chemical safety assessment

Carcinogenicity: via inhalation route

Endpoint conclusion

Dose descriptor:

NOAEC

10 mg/m³

Justification for classification or non-classification

Molybdenum trioxide is classified as carcinogen category 2 according to Commission Regulation (EC) No 790/2009, amending Regulation (EC) No 1272/2008. The placing of a substance in Category 2 is done on the basis of evidence in animal studies, but where the evidence is insufficient to place the substance in Category 1A or 1B.

Additional information

A two year carcinogenicity study (NTP 1997) is available, in which rats and mice were exposed to the test substance molybdenum trioxide via inhalation.

 

Systemic carcinogenicity:

Both in rats and mice (male and female), there was no evidence of systemic carcinogenicity.

 

Carcinogenicity in the lung:

In male rats, NTP concluded on “equivocal evidence of carcinogenic activity” based on a marginally significant positive trend of alveolar/bronchiolar adenoma or carcinoma (combined). There was no evidence of carcinogenic activity of molybdenum trioxide in female rats. According to NTP, “some evidence of carcinogenic activity” of molybdenum trioxide in male mice based on increased incidences of alveolar/bronchiolar carcinoma and adenoma or carcinoma (combined) was found. There was some evidence of carcinogenic activity of molybdenum trioxide in female mice based on increased incidences of alveolar/bronchiolar adenoma and adenoma or carcinoma (combined).

Based on these effects, which are restricted to local effects in the respiratory tract, molybdenum trioxide (MoO3) is classified as a carcinogen category 2 according to Commission Regulation (EC) No 790/2009, amending Regulation (EC) No 1272/2008 for the purposes of its adaptation to technical and scientific progress.

 

 

Discussion: local effects of MoO3 are substance specific and not relevant for molybdenum substances in general

 

When considering the occurrence, severity (or absence) of a localised toxicological effect of a solid chemical substance, chemical structure and reactivity, including the dissolution behaviour in physiological fluids, plays an important role. Molybdenum trioxide has a different chemical structure and reactivity compared to other molybdenum substances. These differences in chemical structure and dissolution behaviour between molybdenum trioxide and sodium molybdate (as an example also for other molybdate salts) are noted below and can account for the local effects of molybdenum trioxide that would not occur with sodium molybdate.

Sodium molybdate and molybdenum trioxide are both compounds of molybdenum in oxidation state six (Mo+6), but their structures are different. In sodium molybdate, molybdenum is bound to four oxygen atoms at the corners of a tetrahedron (Figure 1, based on (4)). The molybdate, MoO42-, ions are isolated one from another in an ionic crystal lattice which also includes balancing sodium ions and water molecules in hydrated forms of sodium molybdate. In contrast, in molybdenum trioxide, molybdenum is coordinated by six oxygen atoms at the corners of an octahedron. The octahedra are linked by oxygen atoms in an infinite lattice (Figure 2, based on (5,6)).  There is a range of Mo – O bond lengths in molybdenum trioxide (6). The longer bonds are those with bridging oxygen; they are weaker, more easily broken, than the shorter bonds and are centres of reactivity of molybdenum trioxide. In sodium molybdate, oxygen atoms are bound to only one molybdenum atom; the Mo – O bonds are shorter and less reactive.

 

 

Figure 1. Structure of sodium molybdate dihydrate (based on reference (4). Atom labelling as shown. The structure consists of isolated molybdate and sodium ions and water molecules in an ionic lattice.  Molybdenum – oxygen bond lengths: 1.85, 1.74, 1.77, 1,68 mean 1.76 Å.

 

Figure 2. Structure of molybdenum trioxide (based on reference (5). Atom labels as shown. The structure is an extended lattice of linked [MoO6] octahedra.

 

The different chemical structures of molybdenum trioxide and sodium molybdate also become apparent in different infrared, UV, visible light and Raman spectra (references 6-13, details not repeated here for the sake of brevity).

 

When in contact with aqueous media, sodium molybdate, an anionic salt, simply dissolves in water giving a solution of pH 7 (14). The process of dissolution is simply the breakup of the ionic lattice.

However, in contrast, molybdenum trioxide per se does not simply dissolve in water. Instead it reacts with water giving an acidic solution, in a reaction in which Mo-O-Mo bonds are broken: MoO3+ H2O --> MoO42-+ 2H+. In a water solubility study according to OECD TG 105, a saturated solution of molybdenum trioxide in purified water had a pH 2.5 at 20°C (15).

 

Such acidity is also observed MoO3 particles dispersed in composites, for example in MoO3 mixed-oxide catalysts. Recent research on the antimicrobial property of MoO3 composites with certain polymers and oxides has attributed their antibacterial effect to acidity. It is plausible to envisage an analogous behaviour of inhaled MoO3 particles interacting with the lung surface and, as a composite, developing an acidic reaction. The antibacterial effect and the lung effect is specific to the MoO3 solids (particles or bound in composites) and is not observed for MoO3 dissolved in water.

Some references relating to the antibacterial properties of MoO3 have been included in the technical dossier in section 7.9.4 (specific investigations: other studies).

 

In conclusion, the reported local effects of MoO3 in the lungs of experimental animals are most plausibly related to the particular chemical structure and reactivity of MoO3 particles which, as indicated above, are different from those of sodium molybdate and other molybdenum substances*. In other words, the local effects of MoO3 are most likely due to a direct particle interaction (reaction) with the lung tissue and not related to the molybdate ion which is present after dissolution of MoO3 or other molybdenum substances.  Read-across of the observed local lung effects of MoO3 to other molybdenum substances* is therefore not justified.

 

* Except to the technical form of molybdenum oxide (CAS No. 86089-09-0, EC name: “molybdenum sulfide (MoS2) roasted”), which is an UVCB with the main constituent being MoO3, and to which the local effects of MoO3 in the lungs of the animals are read-across.

 

Overall, there are no data available that would indicate that the substance discussed in this dossier is carcinogenic and “no classification” is concluded.

 

References

(1) NTP Technical Report On The Toxicology And Carcinogenesis Studies Of Molybdenum Trioxide In F344/N Rats And B6c3f1 Mice (Inhalation Studies) National Toxicology Program April 1997 NTP TR 462 NIH Publication.

(2) Hoffman, G. M. (2011a): Sodium molybdate dihydrate: A 28-day oral gavage and dietary administration dose range finder study in rats. Huntingdon Life Sciences, P. O. Box 2360, Mettlers Road, East Millstone, New Jersey 08875-2360, U. S. A. Unpublished study for the International Molybdenum Association (IMOA). Report No. 10-2205. Report date 2011-08-30.

(3) Hoffman, G. M. (2011b): Sodium molybdate dihydrate: A 90-day oral dietary administration study in rats (GLP). Huntingdon Life Sciences, P. O. Box 2360, 100 Mettlers Road, East Millstone, New Jersey 08875-2360, U. S. A. Unpublished study for the International Molybdenum Association (IMOA). Report No. 10-2225. Report date 2011-10-25.

(4) L. O. Atovmyan and O. A. D'yachenko,  Zhurnal Strukturnoi Khimii,10, 1969, 504.

(5) L. Kihlborg, Ark. Kemi., 1963, 24, 357.

(6) L. Seguin, M. Figlarz, R. Cavagnat and J. -C. Lassegues, Spectrochim. Acta, 1995, 51A, 1323.

(7) http: //webbook. nist. gov/cgi/cbook. cgi?ID=B6000473&Mask=8/0#IR-Spec

(8) A. Stoyanova, R. Iordanova, M. Mancheva andY. Dimitriev, Journal Of Optoelectronics And Advanced Materials, 2009, 11, 1127.

(9) P. C. H. Mitchell, Quart. Rev., 1966, 20, 103

(10) J. H. Ashley and P. C. H. Mitchell, J. Chem. Soc. (A), 1968, 2821

(11) J. H. Ashley and P. C. H. Mitchell, J. Chem. Soc. (A) 1969, 2730;

(11) P. C. H. Mitchell and F. Trifiro, J. Chem. Soc. (A), 1970, 3183;

(13) A. W. Armour, PhD Thesis, Reading 1972)

(14) Baer, C. (2008): Water solubility of sodium molybdate dihydrate. eurofins-GAB GmbH, D-Pforzheim, Germany. Unpublished report for the International Molybdenum Association (IMOA). Report No. 20071507/01-PCSB. Report date 2008-08-28.

(15) Baer, C. (2008): Water solubility of molybdenum trioxide. eurofins-GAB GmbH, D-Pforzheim, Germany. Unpublished report for the International Molybdenum Association (IMOA). Report No. 20071505/01-PCSB. Report date 2008-08-29.