708 R. Golden Table 3. Comparison of IARC, NTP, and US EPA use of or reliance on data from key studies addressed in present review. Study/ issue/findings IARC (2009)a NTP (2010) US EPA/IRIS (2010a) Lu et al. (2009)/)—Lack of Study not available for Background document: Cited only for finding of endogenous exogenous FA-DNA adducts most recent assessment; Acknowledged finding of no FA-DNA adducts; failed to mention at any sites distant to nasal acknowledged as key issue by exogenous FA-DNA adducts at any key finding of no exogenous FA-DNA epithelium Smith and Goldstein (2010)b sites distal to nasal epithelium. adducts detected at any sites distal to Expert panel report: Not mentioned. nasal epithelium. Meng et al. (2010))—No Not available Background document: Not cited Cited only for findings on cell increase in p53 mutations in Expert panel report: Not mentioned proliferation (used with permission nasal epithelium following of authors); did not mention that p53 13 13-wk exposure to FA at mutations not increased after 13 wks up to 15 ppm exposure to FA at 15 ppm Marsh et al. (2004, 2005, Not available Background document: Marsh et al. Marsh 2004: Failed to cite 2007) —Re-analyses of (2007): Misrepresents key findings reanalysis of NCI cohort data on NCI cohort data on NPC on previous exposure to metals and leukemia;Marsh 2007: Inaccurately and leukemia; alternative acids as plausible explanation for characterizes key findings, e.g., explanation for increased increased NPC in Plant #1 in NCI previous exposure to metals and NPC in Plant 1 and cohortExpert panel report: Ignored acids as plausible explanation for implications of significant all Marsh et al. re-analyses of NCI increased NPC in NCI cohort mortality deficits on RR data calculations. Beane Freeman et al. Not available Background document: Findings Inappropriately relied on to support (2009);)—Update of NCI accurately characterizedExpert conclusion of FA-induced increased cohort; reveals >1000 panel report: Incorrectly implied risks of all forms of leukemia (AML, missing deaths in previous study as reporting significant CML, ALL, CLL) and Hodgkin’s studies (Hauptmann et al., increased mortality from AML lymphoma; relied on statistically 2003, 2004) insignificant cumulative exposure findings for cancer risk projections Bachand et al. (2009)— Not available Background document: Findings Not cited or discussed even though Meta-analysis of leukemia accurately characterized for NPL available; sole reliance on Zhang and NPC epidemiology and leukemia.Expert panel report: et al. (2009) cited 44 times as primary data, only meta-analysis Not mentioned or cited. support for interpreting Beane to include Beane Freeman Freeman et al. (2009) findings that et al. (2009) all forms of leukemia and Hodgkin’s lymphoma causally associated with exposure to formaldehyde Conolly et al. (2003, 2004)— Not available Background document: Both Appendices D, E, and F devoted to Biologically based dose studies discussedExpert panel questioning/critiquing basis for and response (BBDR) model for report: Neither study mentioned conclusions from BBDR model FA-induced nasal tumors Andersen et al. (2008, Not available Background document: 2008 study Appendices G and H devoted to 2010)—3 and 13- wk FA mentioned.Expert panel report: questioning/critiquing conclusions inhalation dose-response Neither study mentioned. of dose-response toxicogenomic toxicogenomic studies; data and benchmark dose analysis; Thomas et al. (2007); primary emphasis on Hester et al. benchmark dose analysis (2003, 2005) single dose nasal instillation studies Fox et al. (1985) and Fox: Summarizes FA use at Fox: Summarizes FA use at 4% Neither study cited. Matubayasi et al. (2007)— 4% (40,000 ppm) for tissue (40,000 ppm) for tissue fixation; no Basis for explaining FA fixation; no explanation for explanation for relevance in living toxicity at distant sites due relevance in living systems systems (2 ppm) Matubayasi: Article to methanediol dissociation (2 ppm)c on FA−-methanediol equilibrium in to free FA boiling water FA = formaldehyde. a: Complete report on 2009 meeting not yet available. b: bGoldstein, B.D. and, Smith, M.T. (2010). Formaldehyde. Identification of research needs to resolve the carcinogenicity of high priority IARC carcinogens. IARC Technical Publication No. 42. Lyon, France: IARC. c: cPreliminary IARC report. documents compiled. Although ignoring key data (e.g., Lu et al., 2009; Meng et al., 2009) cannot be condoned, criti- cally reviewing other study findings in light of the totality of data on a particular issue should be a goal, particularly for complex assessments. Simply stated, some studies are better than others and this requires a critical assessment of methods, potential confounders, conclusions, etc. The body of toxicogenomic studies on formaldehyde is a prime example of this, with those conducted via inhalation in a dose-response manner questioned on the basis of uncer- tainty, whereas those using a single nasally instilled dose were accepted due to the reported finding of changes in DNA repair genes. Although a precautionary approach may be justified for assessing risks about chemicals for Critical Reviews in Toxicology