rodents, non-human primates, and humans showing that inhaled formaldehyde does not change endoge- nous levels in the blood has substantial implications for any postulated distant site toxicity. This has now been further confirmed in rodents and non-human primates unequivocally, demonstrating that formaldehyde-DNA adducts derived from exogenous inhalation exposure to 13CD2-formaldehyde are undetectable at any sites distal to the nasal epithelium, making it difficult to explain how adverse effects other than at the point of contact might occur. This is especially relevant when assessing whether inhaled formaldehyde is capable of inducing leukemia. The large database on formaldehyde has been reviewed, summarized, and relied upon by IARC, NTP, and US EPA in their recent evaluations, which have led to firm conclusions concerning the major endpoints of concern as discussed in this review. However, particu- larly for the evaluations from NTP and US EPA, accord- ing to applicable information quality guidelines (i.e., the Information Quality Act [IQA] as well as agency-specific guidelines [US EPA IQA Guidelines]), such “influen- tial” scientific data are subject to a rigorous standard of quality to ensure and maximize the quality, objectivity, utility, and integrity of the information (US EPA, 2002). Instead, on several issues of central importance, partic- ularly with respect to formaldehyde-induced cancers, key study data are either not mentioned or incompletely characterized. The most striking example of this is theUS EPA (2010a) assessment that cited Lu et al. (2010) for the finding of endogenous formaldehyde-DNA adducts in various tissues (a long known phenomenon), but fails to mention that formaldehyde-DNA adducts formed from exogenous inhaled formaldehyde cannot be detected at any target sites distal to the nasal epithelium, including the blood and bone marrow. The same failure to prop- erly characterize these data, which call into question how inhalation of a chemical such as formaldehyde that does not increase tissues levels would be capable of initiating the sequence of events leading to the develop- ment of leukemia, can also be seen in another recent US EPA document (Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment) (US EPA, 2010b) where again, the Lu et al. (2010) data were incorrectly characterized, omitting reference to the absence of no detectible exogenously formed formaldehyde-DNA adducts in the blood or bone marrow. Because this document also addresses the issue of formaldehyde- induced leukemia, this omission is puzzling. The failure to properly characterize the findings of Lu et al. (2010)1 in two recent US EPA documents (2010a, 2010b) on the subject of formaldehyde-induced leukemia raises ques- tions about the basis for positions taken on this conten- tious issue. 1 The Society of Toxicology Board of Publications Best Paper in Toxicological Sciences Award for 2011. © 2011 Informa Healthcare USA, Inc. Indoor air exposure limit for formaldehyde 707 Other data are also not accurately characterized and/ or omitted, including (1) primary reliance on only one (i.e., Zhang et al., 2009) of several meta-data analyses for the conclusion that the equivocal body of epidemiology data are strongly supportive of an association between formaldehyde exposure and leukemia while not cit- ing another meta-analysis (Bachand et al., 2009) that was available and the only one to include the updated analysis of the NCI cohort (i.e., Beane Freeman et al., 2009); (2) failure to note the results from a 13-week study (Meng et al., 2009) demonstrating a lack of increased p53 mutations in nasal tissues following exposure to formal- dehyde suggesting they are not an early driver for later tumorigenesis; only the reported cell proliferation data from this study were discussed and displayed in a table with permission from the authors; (3) uncritical reliance by IARC, NTP, and US EPA on a questionable study in Chinese workers by Zhang et al. (2010) suggesting that formaldehyde exposure produced decreased red and white blood cell counts and elevations in monosomy 7 and trisomy 8 in peripheral cultured stem/progenitor cells and that such findings were predictive of develop- ing leukemia, even though there is no test available in hematology or clinical medicine that has been validated for this purpose. Table 3 is a comparison of some of the positions taken by IARC, NTP, and US EPA on a number of key issues pertaining to the use and interpretation of the available data. As shown in Table 3, not only do NTP and US EPA interpret the same data differently, but also in some instances key data are selectively omitted by NTP while cited by US EPA or vice versa. Table 4 is a com- parison of the studies relied upon as the basis for IARC, NTP, and US EPA conclusions on formaldehyde-induced cancers and the process used for their determinations. The questionable biological plausibility that exog- enous formaldehyde could adversely affect white blood cells or be transported to the bone marrow to cause leu- kemia has been further confirmed by the results reported by Lu et al. (2010a), Moeller et al. (2010), and Swenberg et al. (2010). The lack of transport of exogenous formal- dehyde to the bone marrow in non-human primates with hematopoietic systems virtually identical to humans (Szilagyi et al., 2010) casts more doubt on a conclusion that formaldehyde is a cause of leukemia. In comparing and contrasting the equivocal body of epidemiology data with the data showing unequivocally that inhaled exog- enous formaldehyde-DNA adducts are undetectable beyond the nasal epithelium, one is left with an inescap- able conundrum—both sets of data cannot be correct. Consequently, although it may be appropriate for IARC, NTP, or US EPA to rely, at least in part, on what appear to be precautionary approaches or perhaps policy consid- erations as a basis for concluding that there is a causal association between exposure to formaldehyde and leu- kemia, such conclusions cannot be supported based on the available science and biological plausibility. A corollary to this concerns how studies are reviewed and characterized in some of the large supporting