Indoor air exposure limit for formaldehyde 673 2. Controlled human exposure chamber studies...................................................................................................... 682 3. False-positive reports of formaldehyde-induced sensory irritation.................................................................... 683 E. Sensory irritation effects in children and other potentially sensitive individuals ................................................. 684 F. Asthma.......................................................................................................................................................................... 685 1. Residential indoor air studies................................................................................................................................. 685 2. Other studies and evaluations ................................................................................................................................ 686 G. Data from which to derive an indoor air formaldehyde concentration protective for sensory irritation............ 687 1. Key studies or evaluations ...................................................................................................................................... 687 2. Derivation of recommended value ........................................................................................................................ 689 H. Implications of table 1 for non-cancer effects.......................................................................................................... 690 IV. Cancer effects ................................................................................................................................................................. 690 A. Recent agency reviews of potential formaldehyde carcinogenicity........................................................................ 690 B. Nasopharyngeal cancer (NPC) .................................................................................................................................. 691 1. Animal data.............................................................................................................................................................. 691 2. Mutagenicity Data ................................................................................................................................................... 691 3. Mode of action for nasal tumors............................................................................................................................. 692 4. Biologically based dose-response (BBDR) model ................................................................................................ 692 5. Toxicogenomic data ................................................................................................................................................ 694 6. Human data ............................................................................................................................................................. 695 7. Meta-analysis of NPC data...................................................................................................................................... 697 C. Leukemia ..................................................................................................................................................................... 697 1. Animal data.............................................................................................................................................................. 697 2. Human data ............................................................................................................................................................. 698 3. Meta-analyses of leukemia data............................................................................................................................. 701 4. Leukemia mode-of-action issues ........................................................................................................................... 701 5. Chinese worker study.............................................................................................................................................. 703 6. Potential NPC and leukemia risks based on stable isotope studies .................................................................... 704 7. Formaldehyde hematotoxicity ............................................................................................................................... 704 D. Derivation of an indoor air level of formaldehyde for carcinogenic effects........................................................... 705 V. Discussion ........................................................................................................................................................................ 706 A. Sensory irritation ........................................................................................................................................................ 711 B. Nasopharyngeal cancer (NPC) .................................................................................................................................. 711 C. Leukemia ..................................................................................................................................................................... 713 D. Chance as a potential source of uncertainty in epidemiology studies ................................................................... 713 E. US EPA’s projected cancer risks from inhaled formaldehyde .................................................................................. 714 VI. Conclusions.................................................................................................................................................................... 714 Acknowledgments................................................................................................................................................................... 715 Declaration of interest............................................................................................................................................................. 716 References................................................................................................................................................................................ 716 I.Introduction Over the past four decades, formaldehyde has been the subject of extensive scientific study due to (1) its long rec- ognized irritant properties, (2) the discovery that inhaled formaldehyde could induce nasal tumors in rodents, and (3) some findings from epidemiology studies suggesting that formaldehyde might be capable of increasing the risk of certain cancers in humans as well. Numerous compre- hensive reviews addressing all aspects of formaldehyde toxicity and potential for adverse health effects have been conducted by regulatory and other authoritative bod- ies from around the world, including the International Agency for Research on Cancer (IARC, 2003, 2009), the National Toxicology Program (NTP, 2009), the Agency for Toxic Substances and Disease Registry (ATSDR, 1999), the US Environmental Protection Agency (US EPA, 2010a), the © 2011 Informa Healthcare USA, Inc. National Academy of Sciences (NAS, 2007), Health Canada (2005), Germany’s Federal Institute for Risk Assessment (BfR) (2006), Australia’s National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (2005), the European Union’s Scientific Committee for Occupational Exposure Limits (SCOEL), and the World Health Organization (WHO, 2002, 2010). The number of published scientific papers on various aspects of formal- dehyde-related issues is now in the thousands. Formaldehyde continues to receive substantial pub- licity due, at least in part, to its presence in the indoor air of Federal Emergency Management Agency (FEMA) trailers (i.e., temporary housing units supplied to the vic- tims of Hurricanes Katrina and Rita in New Orleans and Mississippi) (ATSDR, 2007a, 2007b). This publicity has involved both non-cancer effects such as sensory irrita- tion of the eyes, nose, and throat as well as allegations