Indoor air exposure limit for formaldehyde 709 Hauptmann et al. (2009) Pinkerton et al. (2004) Table 4. Comparison of the basis for IARC, NTP, and US EPA conclusions on formaldehyde-induced cancers. Study/ issue/ findings IARC (2009)a NTP (2010) US EPA/IRIS (2010a) Comment How Vote of working group: Vote of Expert Panel: Single 11 to 0 Key selected studies Single NTP vote for all conclusions 11 to 9 for leukemia vote for AML, NPC, and SNC with little if any endpoints presumes reached critical assessment of same strength of evidence methodological issues. for all endpoints. Major Leukemia and NPC AML, NPC, and sinonasal cancer AML, CML, ALL, CLL, Only NTP concluded conclusions AML: Beane Freeman (2009), Hodgkin’s lymphoma, that sinonasal cancer an and key studies Hauptmann (2009), Coggin and NPC Beane Freeman endpoint associated with relied on as (2003), and Pinkerton (2004); 3 (2009), Zhang (2009, 2010), FA exposure; US EPA/ primary support of 4 studies found elevated risks Hauptmann (2004) IRIS uses statistically of AML in individuals with high insignificant cumulative exposure to FA, as well as positive exposure data from exposure-response relationships. Beane Freeman as basis NPC: Hauptmann 2004; the only for yearly incidence cohort study that is individually projections for all informative for NPC leukemia, Hodgkin’s lymphoma and NPC Beane Freeman Primary support for AML not significantly elevated Does not support No consideration of et al. (2009); leukemia based on peak, no. of peaks, conclusion of FA-induced numerous issues with most recent cumulative, duration, or average increased risks of all forms study; no mention of update of NCI intensity of exposure; no significant of leukemia (AML, CML, implications of >1000 cohort trends ALL, CLL) and Hodgkin’s missed deaths lymphoma; insignificant cumulative exposure findings used for cancer incidence risk projections Coggin et al. No significant increase in all forms No significant increase in all Little, if any, emphasis on (2003) of leukemia; myeloid leukemia not forms of leukemia; myeloid study findings as basis for separately evaluated leukemia not separately conclusions evaluated; No significant increase in NPC or all forms of leukemia; myeloid leukemia not separately evaluated Myeloid leukemia Myeloid leukemia significantly Myeloid leukemia Little, if any, emphasis on significantly elevated elevated 20+ years after first significantly elevated 20+ study findings as basis for 20+ years after first exposure; test for trend not positive; years after first exposure; conclusions exposure; test for trend no NPC cases test for trend not positive; not positive; no NPC no NPC cases. cases. Not cited in IARC Duration of embalming practice Duration of embalming Formaldehyde exposure (2009). Formaldehyde associated with significantly practice associated with not measured; number of 4. Mechanistic and increased risk for mortality from significantly increased risk embalming a surrogate other relevant data. Vol. myeloid leukemia; myeloid for mortality from myeloid for exposure; major issue 100F, Monograph No. leukemia significantly associated leukemia; myeloid leukemia concerns failure to test 09-Formaldehyde, with increasing number of years significantly associated key results for statistical of embalming (p trend = .020) and with increasing number significance with increasing peak formaldehyde of years of embalming exposure (p trend = .036). (ptrendP trend = .020) and with increasing peak formaldehyde exposure (ptrendP trend = .036). Hauptmann et al. (2004) Primary support for NPC Primary support for NPC Hauptmann et al. (2003) Reported leukemia findings not accurate due to failure to account for >1000 missing deaths © 2011 Informa Healthcare USA, Inc. Reported leukemia findings not accurate due to failure to account for >1000 missing deaths Primary support for NPC Most reviews dismiss or ignore analysis by Marsh et al. (2007) showing previous exposure to known NPC risk factors a likely explanation for reported results Reported leukemia findings Analyses by Marsh et al. not accurate due to failure (2004, 2007) demonstrate to account for >1000 missing substantial attenuation of deaths risks after accounting for >1000 missing deaths Table 4. continued on next page