710 R. Golden Table 4. Continued. Study/ issue/ findings IARC (2009)a NTP (2010) Zhang et al. Cited in bibliography; “...more informative because it (2009); meta- no indication how used used data for individuals with the analysis to reach conclusions. highest exposure to formaldehyde to calculate the summary relative risks.” Zhang et al. Support for biological Support for biological plausibility Support for biological Numerous (2010); Chinese plausibility of of epidemiology results; no critical plausibility of epidemiology methodological and worker study epidemiology results; assessment of methods or assertion results; no critical interpretive issues no critical assessment that FA equivalent to benzene in assessment of methods or undermine study; no of methods or assertion leukemogenic potential assertion that FA equivalent critical assessment of that FA equivalent to benzene in leukemogenic reported conclusions. to benzene in potential leukemogenic potential US EPA/IRIS (2010a) Comment Cited 44 times to support Findings at odds with reliance on Beane Freeman 2 other meta-analyses (2009) results for all including Bachand et al. leukemia and Hodgkin’s (2009), which is only one lymphoma to include the Beane Freeman results. Tang et al. Support for FA-induced Support for FA-induced (2009); review hematotoxicity; hematotoxicity; reported results of studies reported results uncritically accepted. purporting to uncritically accepted. demonstrate FA-induced hematotoxicity Fox et al. Cited to explain how Cited to explain how methanediol (1985); basis methanediol could could dissociate at distant sites to for claiming dissociate at distant release free FA as explanation for FA toxicity at sites to release free leukemia distant sites due FA as explanation for to methanediol leukemia dissociation to free FA Matubayasi et al. Cited to explain how Cited to explain how methanediol (2007); basis methanediol could could dissociate at distant sites to for claiming dissociate at distant release free FA as explanation for FA toxicity at sites to release free leukemia distant sites due FA as explanation for to methanediol leukemia dissociation to free FA Support for FA-induced All but one study in hematotoxicity; reported Chinese; only study results uncritically accepted. in English does not support FA-induced hematotoxicity Not cited; still implies that FA or methanediol may reach sites distal to portal of entry Not cited; still implies that FA or methanediol may reach sites distal to portal of entry Article on use of 4% formalin for tissue fixation (40,000 ppm); not relevant for living systems (2 ppm) Article about methanediol dissociation in boiling water; no relevance for living systems. FA = formaldehyde. aComplete report on 2009 meeting not yet available. bGoldstein BD, Smith MT. (2010). Formaldehyde. Identification of research needs to resolve the carcinogenicity of high priority IARC carcinogens. IARC Technical Publication No. 42. Lyon: IARC. cPreliminary IARC report. which there are sparse data, lack of data is hardly the case for formaldehyde. This is also why it is surprising to see the results of the controlled human exposure studies on formaldehyde-induced sensory irritation essentially ignored in favor of studies where reported results cannot be reliably attributed solely to formaldehyde. The same appears to be the case for the criticisms of the BBDR model, the conclusions of which have been accepted by numerous reviewing entities including NAS (2007). As briefly summarized above, an NRC committee (NAS 2011) recently completed its evaluation of the EPA’s draft IRIS assessment of formaldehyde reaching many of the same conclusions as this review. This criti- cal assessment “…found that the draft was not prepared in a consistent fashion; it lacks clear links to an underlying conceptual framework; and it does not contain sufficient documentation on methods and criteria for identifying evidence from epidemiologic and experimental studies, for critically evaluating individual studies, for assessing the weight of evidence, and for selecting studies for deri- vation of the RfCs and unit risk estimates.” This was par- ticularly the case for the studies selected and relied upon to derive the RfCs for sensory irritation and asthma. The committee was also critical about EPA’s efforts to mar- ginalize the BBDR model with “manipulations of model parameters that yield results that are logically implau- sible” and instead concluded that “Given that the BBDR model for formaldehyde is one of the best-developed BBDR models to date, the positive attributes of BBDR models generally, and the limitations of the human data, the committee recommends that EPA use the BBDR model for formaldehyde in its cancer assessment, compare the results with those described in the draft assessment, and discuss the strengths and weaknesses of each approach.” Readers are encouraged to peruse the NRC review for additional insights of the committee pertaining to the EPA/IRIS assessment (http://www.nap.edu/catalog. php?record_id=13142.) Critical Reviews in Toxicology