Environ. Sci. Technol. 2009, 43, 5549–5550
Response to Comment on “Speciation Analysis of Gadolinium Chelates in Hospital Effluents and Wastewater Treatment Plant Sewage by a Novel HILIC/ICP-MS Method” In their comment on our manuscript “Speciation Analysis of Gadolinium Chelates in Hospital Effluents and Wastewater Treatment Plant Sewage by a Novel HILIC/ICP-MS method” (1), Lawrence and Ort criticize our conclusions related to the behavior of the contrast agents during wastewater collection and treatment and point out that they are derived from a limited set of nonrepresentative samples. It should be noted, however, that the manuscript under discussion is not claiming to be a detailed or even a representative study on the behavior of the contrast agents in hospital effluents or in wastewater-treatment plants, but rather to introduce an innovative method for the determination of different Gd-based contrast agents, which previously was not possible with any other published method. We have taken a very limited number of samples at different times and places to prove that the new method can be applied for the respective types of samples. Therefore, we have formulated all conclusions only as suggestions in a very careful way to avoid overinterpretation of the data. This can clearly be recognized in our wording as cited by Lawrence and Ort. Most of the points Lawrence and Ort raise (1-5) are based on the fact that our samples are not representative for the sampling locations. As stated above, we fully agree with this fact, which was never the goal of our work. However, a thorough and possibly representative study for these two highly variable groups of samples with different sampling locations would require to take at least several hundreds of samples at different times and different locations. It would also have to consider all fluxes in the hospital and the wastewater-treatment plant (WWTP) which are strongly varying based on the day of the week (less or no MRI recorded in the weekends), the time of the day and, in particular for the WWTP, the weather conditions (dilution of the effluents due to precipitation). Such activities do by far exceed the focus of an analytical method development publication as in this case. Points 4-6, however, as raised by Lawrence and Ort, clearly indicate the need for a speciation-analysis method. In point 4, they cite two papers (2, 3), which shall contradict our findings. These two publications are very careful and thorough studies, but they are based on the determination of total Gd by ICP-MS. Therefore, only the concentration of total dissolved Gd is determined. These studies do not allow to draw any conclusions on the chemical binding forms, in which Gd is present. Based on the chemical stability of the contrast agents, it is likely that their lifetime is very long and that indeed the contrast agent concentrations are significant, but in the recent literature, transmetalation effects of Gd-based contrast agents have been observed in simulation experiments (4). This transmetalation is dependent on the individual contrast agent. Transmetalation is also an assumed reason for the pathogenesis of the nephrogenic systemic fibrosis (5-7) (NSF), a severe disease, which has been observed in dialysis patients, who were subject to a MRI under the use of Gdbased contrast agents with linear ligands. For macrocyclic ligands, which form kinetically more stable complexes with 10.1021/es901550c CCC: $40.75
Published on Web 06/18/2009
2009 American Chemical Society
Gd(III) (8), this disease has not been observed yet. Therefore, the inherent assumption that the lifetime of the contrast agents in wastewaters or in the aquatic ecosystem is infinite (see below in the discussion of the equation), should be reinvestigated. Possible chemical processes, which might influence the contrast agent concentration, could be transmetalations (9-11) with ions as for example Fe(III), ligand-exchange reactions with other complexing agents as the frequently used EDTA, or metabolic reactions under modification or decomposition of the ligands. With the currently used ICP-MS methods, precise total Gd measurements in wastewaters and surface waters are possible, but a reduction in the contrast agent concentration could only be found if any reaction product would be removed from the liquid-phase sample, e.g., by adsorption or precipitation. Therefore, equations as [GdTot] ) Σ[GdCAs] + [Gdnat] as mentioned by Lawrence and Ort under point 6, simplify the chemical situation in a very doubtful way, as they claim that there will only be native Gd and the sum of contrast agents in aqueous samples. This has never been proven and even could not be proven with the available analytical methods. Only speciation analysis of the different Gd binding forms will be able to shed light on this situation, and the combination of analytical separation techniques with ICP-MS (11) is one particularly promising way to go. The goal of our work was and is to provide valuable analytical tools, which allow a better understanding of the difficult chemical situation of Gd-based contrast agents in wastewaters and surface waters.
Literature Cited (1) Ku ¨ nnemeyer, J.; Terborg, L.; Meermann, B.; Brauckmann, C.; Mo¨ller, I.; Scheffer, A.; Karst, U. Speciation analysis of gadolinium chelates in hospital effluents and wastewater treatment plant sewage by a novel HILIC/ICP-MS method. Environ. Sci. Technol. 2009, 43, 2884–2890. (2) Kulaksiz, S.; Bau, M. Contrasting behaviour of anthropogenic gadolinium and natural rare earth elements in estuaries and the gadolinium input into the North Sea. Earth Planet. Sci. Lett. 2007, 260, 361–371. (3) Mo¨ller, P.; Dulski, P.; Bau, M.; Knappe, A.; Pekdeger, A.; Sommer-von Jarmersted, C. Anthropogenic gadolinium as a conservative tracer in hydrology. J. Geochem. Explor. 2000, 69, 409–414. (4) Puttagunta, N. R.; Gibby, W. A.; Puttagunta, V. L. Comparative transmetallation kinetics and thermodynamic stability of gadolinium-DTPA bis-glucosamide and other magnetic resonance imaging contrast media. Invest. Radiol. 1996, 31, 619– 624. (5) Cowper, S. E.; Robin, H. S.; Steinberg, L. D.; Su, S.; Gupta, P. E. LeBoit, Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000, 356, 1000–1001. (6) Boyd, K. E.; Xiao, Y. Y.; Fan, K.; Poholek, A.; Copeland, N. G.; Jenkins, N. A.; Perkins, A. S. Gadolinium deposition in nephrogenic fibrosis dermopathy. Blood 2006, 107, 733–741. (7) Marckmann, P.; Skov, L.; Rossen, K.; Dupont, A.; Damholt, M. B.; Heaf, J. G.; Thomsen, H. S. Nephrogenic systemic fibrosis: Suspected caustive role of gadodiamide used for contrast-enhanced magnetic resonance imaging. Am. Soc. Nephrol. 2006, 17, 2359–2362. (8) Frenzel, T.; Lengsfeld, P.; Schirmer, H.; Hu ¨ tter, J.; Weinmann, H.-J. Stability of gadolinium-based magnetic resonance VOL. 43, NO. 14, 2009 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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imaging contrast agents in human serum. Invest. Radiol. 2008, 43, 817–828. (9) Idee, J. M.; Port, M.; Raynal, I.; Schaefer, M.; Le Greneur, S.; Corot, C. Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: A review. Fundam. Clin. Pharmacol. 2006, 20, 563– 576. (10) Morcos, S. K. Nephrogenic systemic fibrosis following the administration of extracellular gadolinium based contrast agents: is the stability of the contrast agent molecule an important factor in the pathogenesis of this condition. Br. J. Radiol. 2007, 80, 73–76. (11) Ku ¨nnemeyer, J.; Terborg, L.; Nowak, S.; Scheffer, A.; Telgmann, L.; Tokmak, F.; Gu ¨ nsel, A.; Wiesmu ¨ ller, G.; Reichelt, S.; Karst,
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Jens Ku ¨ nnemeyer, Lydia Terborg, Bjo ¨ rn Meermann, Christine Brauckmann, Ines Mo ¨ ller, Andy Scheffer, and Uwe Karst Westfa¨lische Wilhelms-Universita¨t Mu ¨ nster, Institut fu ¨r Anorganische und Analytische Chemie, Corrensstr. 30, 48149 Mu ¨ nster, Germany ES901550C
