Letter to the editor in response to 'Low-dose metabolism of benzene in humans: science and obfuscation' rappaport et al. (2013)

In the paper ‘Low-dose metabolism of benzene in humans: science and obfuscation’ (1), Dr Rappaport and his coauthors vigorously defend the findings of the 2006 publications (2,3) against the points raised in our 2012 publication ‘A reanalysis of the evidence for increased efficiency in benzene metabolism at airborne exposure levels below 3 p.p.m.’ (4). The work leading to Price et al. was driven by the contradiction of the Kim et al. findings of 9to 11-fold enhancement of metabolism of benzene at low doses and multiple published reports of lung clearance (5–7) that suggest only a 2-fold change in metabolism with dose. As shown below, this contradiction is confirmed by the information presented in Rappaport et al. We support the right of Dr Rappaport and his coauthors to question the technical merits of our work or any work in the public domain and to defend Kim et al. (2,3), but we strongly object to the authors’ wording in the title and in the paper’s concluding paragraph. Although the analyses in the Price et al. paper may have been complex, they were clearly presented and subjected to the peer review process. Furthermore, we published the raw data from the study so that experts could replicate the analyses and come to their own conclusions, which is something Kim et al. (2,3) did not do. We included factors in our reanalysis that favor a finding of increased metabolism at low doses as well as others that do not. Thus, we clarified and made transparent legitimate technical issues with the analyses of Kim et al. (2,3) and did not ‘obfuscate’ the original findings. It is unfortunate that Rappaport et al. attempted to disparage our analyses with allegations regarding both our motivations and our professional ethics in expressing our concerns with the Kim et al. data sets and analyses. After reviewing Rappaport et al., we still contend that (i) methodological errors were made in Kim et al. (2,3), (ii) the uncertainties in the predictions of the dose-specific metabolites are too large to determine changes in benzene metabolism at air levels below 0.2 p.p.m. and (iii) biases related to the definition of background are the likely cause of the finding of enhanced metabolism at low doses. As the following text demonstrates, Rappaport et al. have not refuted the first two findings and have confirmed the third finding.