Correspondence Comment on “Intake of Iodine and Perchlorate and Excretion in Human Milk” In Dasgupta et al. (1), the authors provide valuable new data expanding our knowledge of perchlorate, thiocyanate, and iodide excretion into human milk. I am the author or coauthor of three citations (2-4) in Dasgupta et al. and am commenting at this time because of significant misrepresentations of these in their report. Dasgupta et al. Fail to Distinguish between PerchlorateMediated Inhibition of Iodine Uptake and Perchlorate Transport. Regarding Tonacchera et al. 2004 (2), Dasgupta et. al state that the study concluded that “perchlorate is transported by the NIS with a selectivity 30-fold greater than that for iodide.” Tonacchera et al. did not measure perchlorate transport but rather controlled the concentration of the various anions in the milieu contacting the NIS, and measured the relative potencies for iodide, thiocyanate and perchlorate to block radioactive iodine uptake (RAIU) by the NIS. Dasgupta et al. Further Mischaracterize Tonacchera et. al. The authors characterize the NIS in the cell culture study as nonhuman and state “the experiments were generally conducted with high levels of transported ion concentrations...” The CHO cell culture line utilized by Tonacchera et al. was transfected with human NIS. Perchlorate concentrations utilized ranged from 0.01 µmol/ L, equivalent to a dose of approximately 1 µg/kg-day (3), and spanned 4 orders of magnitude higher, resulting in 100% inhibition of RAIU. Thiocyanate concentrations also ranged from 0.01 to 100 µmol/L, spanning all but the highest range of serum thiocyanate concentrations reported in the human literature. The results reported by Tonacchera et al. are consistent with a mechanism of simple competition by three different monovalent anions with similar size for access to the NIS sites on the cell membrane. Estimates from this study of the molar concentrations corresponding to 50% RAIU inhibition were in the ratios of 1:15:30 for perchlorate, thiocyanate, and iodide respectively. These values are in good agreement with the values reported in six other published studies cited in Tonacchera et al. based upon other test systems, including both in vitro and whole animal systems. Dasgupta et al. Do Not Adequately Distinguish between Dose and Concentration. Dasgupta et. al estimated total daily dose of perchlorate and thiocyanate based on excretion measurements but did not measure serum concentrations. They appear to assume that relative doses are comparable to relative concentrations. To compare the concentration relative potencies from Tonacchera et al. to relative potencies on a dose basis, the serum half-lives (approximately 8 h and 6 days for perchlorate and thiocyanate, respectively) become important because thiocyanate stays in the serum nearly 20 times longer than perchlorate. After adjusting for molecular weights, the iodine uptake inhibition (IUI) potency of thiocyanate on a dose basis is double that of perchlorate (2). In their Table 1, Dasgupta et. al present perchlorate dose in µg/kg/day and thiocyanate dose in µg/day for nursing infants. Using their supplemental data available for infant age and gender and Table 1-11 from the USEPA Child-Specific Exposure Factors Handbook, individual infant weights can be estimated in the manner described in Dasgupta et al. (1). The mean and median infant 2654
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thiocyanate doses thus calculated are 10.8 and 5.2 µg/ kg/day respectively, approximately 10 times higher than their reported perchlorate doses. The calculated IUI of thiocyanate is thus 20 times that of perchlorate. The authors of Dasgupta et al. conclude, however, that “the role of thiocyanate as an iodide transport inhibitor in milk, especially vis-a´-vis perchlorate, should not be overemphasized....” Dasgupta et al. Fail to Recognize Published Effects of Thiocyanate on Breast Milk Iodine. Gibbs 2006 (3) is primarily a compilation of results from 15 published human studies, each of which includes some estimate of serum thiocyanate concentration and some measure of thyroid function. Thyroid effects ranged from nondetectable to complete thyroid function suppression, while serum thiocyanate concentrations ranged from 20 to 2000 µmol/ L. Notably, one of the human studies included in this analysis, Laurberg et. al 2004 (5) is also cited by Dasgupta et al. Laurberg et al. measured maternal serum thiocyanate and milk iodine concentrations among nonsmoking (n ) 90) and smoking (n ) 50) mothers and their infants in the first few days after delivery. Mean serum thiocyanate in nonsmokers and smokers was 54.7 and 84.9 µmol/L (p < 0.001) and the geometric mean milk iodine concentrations were 53.6 and 26.0 µg/L respectively (p < 0.001). This is a 50% reduction in milk iodine concentrations associated with a 50% increase in serum thiocyanate within the range experienced by nursing mothers. Regarding whether or not thiocyanate is a significant source of IUI, the authors of Dasgupta et al. state that the “merit of this argument with specific reference to breast fed infants may be doubtful.” Dasgupta et al. Do Not Use Valid Statistical Measures to Support a Major Assertion. The authors assert that comments that I coauthored (4) in Kirk et al. 2005 (6) regarding their interpretation of breast milk iodine and perchlorate data were in error, and that their new data vindicates their previous assertions. They use their Figures 3a and b to support their argument that because “no datum fell within the high perchlorate high iodide quadrant.... this continues to suggest that in real mothers perchlorate does inhibit the transport of iodine into milk...” Their data in Figure 3a supports that both the milk iodide and milk perchlorate distribute log-normally and it is clear in that figure that a significant proportion of the data do lie in the high iodine high perchlorate quadrant (as defined by the medians of 7.3 and 43 µg/L presented for their current study for perchlorate and iodide, respectively). The authors rely on the visual illusion in their Figure 3b to make their assertion, without statistical analysis, and without explanation for the break in the x-axis, or even what the perchlorate scale is below 200 µg/L!
Acknowledgments Funding for these comments was provided by the Perchlorate Study Group. Reprints of Tonacchera et al. 2004 and Gibbs 2006 are available by contacting me at jpgibbs@ hughes.net.
Literature Cited (1) Dasgupta, P. K.; Kirk, A. B.; Dyke, J. V.; Ohira, S. Intake of iodine and perchlorate and Excretion in Human Milk. Environ. Sci. Technol. 2008, 42, 8115–8121. (2) Tonacchera, M.; Pinchera, A.; Dimida, A.; Ferrarini, E.; Agetti, P.; Vitti, P.; Ferruccio, S.; Crump, K.; Gibbs, J. Relative 10.1021/es8031538 CCC: $40.75
2009 American Chemical Society
Published on Web 02/27/2009
potencies and additivity of perchlorate, thiocyanate, nitrate and iodine on the inhibition of radioactive iodine uptake by the human sodium iodine symporter. Thyroid 2004, 14, 1012– 19. (3) Gibbs, J. P. A comparative toxicological assessment of perchlorate and thiocyanate based on competitive inhibition of iodide uptake as the common mode of action. Human Ecol. Risk Assess. 2006, 12, 157–173. (4) Lamm, S. H.; Feinleib, M.; Engel, A.; Gibbs, J. Comment on “Perchlorate and Iodide in Dairy and Breast Milk”. Environ. Sci. Technol. 2005, 39, 5900–5901.
(5) Laurberg, P.; Nøhr, S. B.; Pedersen, K. M.; Fugslang, E. Iodine nutrition in breast-fed infants is impaired by maternal smoking. J. Clin. Endocrin. Metabol. 2004, 89, 181–187. (6) Kirk, A. B.; Martinelango, K.; Dutta, A.; Tian, K.; Smith, E. E.; Dasgupta, P. K. Perchlorate and iodide in dairy and breast milk. Environ. Sci. Technol. 2005, 39, 2011–2017.
John P. Gibbs 300 Fischer Store Road, PO Box 2948, Wimberley, Texas 78676 ES8031538
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