To the Editor:
We read with interest the recent discussion of cobalt blood value interpretation by Paustenbach and colleagues at Cardno ChemRisk.Citation1 We applaud their attempt to clarify the clinical usefulness of cobalt values in biologic samples and found their review informative. However, we do have several questions regarding the application of their pharmacokinetic model to the behavior of cobalt-chromium (Co-Cr) nanoparticles, the wear products of metal-on-metal hip implants.
Like many metals, the blood cobalt value at which systemic effects occur probably depends on many factors. We agree with the authors that the 7 μg/L threshold established by the MHRA is not correlated with disease and may not be applicable to a North American population. The authors state that “the available data show that blood cobalt concentrations of at least ˜300 μg/L are unlikely to pose a risk of adverse health effects.” The primary data cited by the authors to support this conclusion is historic cases of toxicity from cobalt ions and the biokinetic model derived by Cardno ChemRisk.Citation2
Cardno ChemRisk's model relies heavily on studies of oral cobalt salt ingestion. Metal nanoparticles and metal ions do not typically behave similarly. This has been demonstrated when comparing cobalt nanoparticles to their ionic counterparts.Citation3 In nanoparticle pharmacokinetic modeling, the physiochemical properties of nanoparticle size, size distribution, shape, surface area and structure, surface chemistry, chemical composition, overall charge, solubility, and agglomeration rate are instrumental in determining distribution and predicting toxicity.Citation4 Do the authors feel this limits the applicability of their model to predicting systemic effects from metal-on-metal hip implants?
Additionally, there may be latency between exposure, peak blood values, and the onset of symptomatic disease in metal toxicology. For example, in the famous case of Dr. Karen Wetterhan's fatal dimethylmercury exposure, hair sampling and pharmacokinetic modeling determined that her original total body burden of mercury was four times the value apparent at the time she became symptomatic.Citation5 Do the authors feel this impacts their suggestion that a blood value less than 300 μg/L should not be associated with systemic effects from metal-on-metal hip implants?
The authors state that “it is quite possible that blood cobalt concentrations will not correlate with implant failure.” Do the authors also believe it is possible that blood cobalt values will not correlate with hip implant-associated systemic effects? Recently, Pizon et al. suggested that clinicians consider elevated blood cobalt values evidence of exposure and search for evidence of toxicity with objective testing in symptomatic patients.Citation6 Do the authors agree with this approach?
Declaration of interest
The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References
- Paustenbach DJ, Galbraith DA, Finley BL. Interpreting cobalt blood concentrations in hip implant patients. Clin Toxicol (Phila) 2014; 52:98–112.
- Unice KM, Monnot AD, Gaffney SH, Tvermoes BE, Thuett KA, Paustenbach DJ, Finley BL. Inorganic cobalt supplementation: prediction of cobalt levels in whole blood and urine using a biokinetic model. Food Chem Toxicol 2012; 50:2456–2461.
- Horev-Azaria L, Kirkpatrick CJ, Korenstein R, Marche PN, Maimon O, Ponti J, et al. Predictive toxicology of cobalt nanoparticles and ion: comparative in vitro study of different cellular models using methods of knowledge discovery from data. Toxicol Sci 2011; 122:489–501.
- Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nanolevel. Science 2006; 311:622–627.
- Nierenberg DW, Nordgren RE, Chang MB, Siegler RW, Blayney MB, Hochberg F, et al. Delayed cerebellar disease and death after accidental exposure to dimethylmercury. N Engl J Med 1998; 338:1672–1676.
- Pizon AF, Abesamis M, King AM, Menke N. Prosthetic hip associated cobalt toxicity. J Med Toxicol 2013; 9:416–417.