Monday, July 4, 2011

Systemic effects of metal debris (7N of 7); excerpts from the Committee on Mutagenicity

Excerpts and commentary based on the 6/4 post-Metal on Metal Bearings, The Evidence So Far

Genotoxic issues surrounding systemic effects of metal debris (continued from prior posts)

The committee on mutagenicity has reported that internal exposure to orthopedic metals is associated with increased genotoxicity.

This is a series of commentary from the committee on mutangenicity evidence based on the the key journal articles examined by that committee. I think you will find the results really interesting if you are concerned about the systemic effects of the metal.

I said this would be the last in this series however, there seem to be 6 items provided in confidence and I am going to try to locate the source data (more time so I myself would like to take time to review each one daily.

6th and final group of comments from the committee (In confidence data sumbitted by the BIRC)...[6 individual comments provided.. 6-11] 

6 of 6

Members of the committee briefly discussed potential mechanisms by which metal ions could induce the effects on DNA repair and fidenlity and inductionof oxidatvie DNA damage.  It was agreed that the biomonitoring and war debris studies provided has not provided convincing evidencee for an interaction between the metals or for metal specifica mutagenic effects.  However the possiblity of interactions between metal ions with regard to mutagenic effects could not be discounted.

Mutat Res. 2003 Dec 10;533(1-2):135-52.

Cobalt and antimony: genotoxicity and carcinogenicity.


Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, Brussel 1050, Belgium.

Erratum in

  • Mutat Res. 2004 Apr 14;548(1-2):127-8.


The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with DNA repair systems, still need further investigation.

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