for children “…because there is no indication that chil- dren are more susceptible to formaldehyde exposure than adults.” Nonetheless, the potential for children’s greater sensitivity deserves further research. The same holds true for other potentially sensitive popu- lations such as the elderly or infirmed individuals who may spend the majority of their time indoors. Although certain metabolic functions decline with age (e.g., Vestal, 1982; Reaven and Reaven, 1980; Schumacher, 1980; Michielsen and Vande, 2010), thereby possibly influencing metabo- lism-related responses, these factors are far less likely to contribute to sensory irritation. There do not appear to be empirical data suggesting age-related changes in response to sensory irritants. Moreover, as previously discussed, time spent at a specific formaldehyde concentration does not appreciably influence the severity of the symptoms produced. As noted by NAS (2007), “Individual suscepti- bility to formaldehyde appears to be difficult to predict, and typically sensitive groups, such as asthmatic individuals, do not appear to be any more sensitive to irritation effects than healthy subjects at exposure concentrations below 3 ppm.” That conclusion is supported by BfR (2006), “There is, how- ever, no indication that a higher sensitivity is present for locally acting substances at the portal of entry, in particular when the effect is related to the concentration, as it is the case for formaldehyde.” As further evidence of this, in con- trolled studies, volunteers who claimed to be sensitive to formaldehyde eye irritation were exposed to levels of 0.35 to 1.0 ppm for 6 minutes. At formaldehyde concentrations of less than 1 ppm, eye irritation responses in sensitive test subjects were no different than with exposure to clean air, whereas at concentrations of 1 ppm, responses ranged from slight to moderate (Bender, 2002). Another consideration for potentially sensitive indi- viduals concerns the issue of polymorphisms in metabo- lizing enzymes such as aldehyde dehydrogenase (ADH). For example, individuals with a genetic polymorphism for the slow form of aldehyde dehydrogenase (ADH2), which is in virtually all tissues, may be more sensitive to the irritant effects of acetaldehyde because of slower removal from upper respiratory tract tissues (Deitrich et al., 2007). This aspect of sensitivity was considered in establishing air levels in submarines for acetaldehyde by the use of an uncertainty factor of 2 (NRC, 2009). However, this situation would not appear to be relevant for formaldehyde, which is principally metabolized by a different aldehyde dehydrogenase (i.e., ADH3), for which polymorphic forms have not been identified. F.Asthma Asthma, particularly in children, is often mentioned as an endpoint of concern with respect to either being caused or exacerbated by the irritant properties of formalde- hyde. Although there are isolated reports of associations between formaldehyde and asthma-like symptoms, they are generally based on small, poorly controlled studies that do not show dose-response relationships between formaldehyde and asthma or surrogate measures (e.g., © 2011 Informa Healthcare USA, Inc. Indoor air exposure limit for formaldehyde 685 atopy) or that report results at implausible formaldehyde concentrations (e.g., low ppb). With respect to many of the studies reporting potential associations between formaldehyde exposure and asthma, it is noteworthy that many types of non-specific exposures (e.g., cold air, nuisance dust, molds, etc.) can initiate asthma-like complaints. Because of this, the potential contribution of other factors cannot reliably be confirmed or ruled out. This difficulty in establishing causal relationships is particularly a problem when residential or occupa- tional studies report asthma-related associations with formaldehyde in cases where all subjects were also simultaneously co-exposed to numerous other airborne contaminants. 1.Residential indoor air studies Studies by Garrett et al. (1999) and Rumchev et al. (2002, 2004) are often cited as a basis for concluding that form- aldehyde is a cause of asthma and atopy. The case-control study by Garrett et al. (1999) involved a total of 148 chil- dren, 53 of whom were asthmatic prior to participation in the study. Consequently, causal associations between anything (including formaldehyde) and asthma cannot be proven by this study. Although provoking symptoms in asthmatic children might hypothetically be related to indoor air levels of any number of substances, with median indoor formaldehyde level in this study of 12.6 ppb (maximum of 111 ppb), it is questionable whether such levels of formaldehyde alone would be associated with provoking symptoms. Although there was an asso- ciation between formaldehyde exposure and atopy, this was not significant (odds ratio [OR] = 1.4, 95% confidence interval [CI] 0.98–2.0) and there was “…no significant increase in the adjusted risk of asthma or respiratory symptoms with formaldehyde exposure.” It is noteworthy that another study on this same cohort of children is often not considered with respect to this issue. In this study (Garrett et al., 1998), indoor airborne fungal spores were assessed in conjunction with asthma and atopy. Asthma was significantly associated with exposure to Penicilium in winter (OR = 1.43, 95% CI 1.03–2.00) and atopy signifi- cantly associated with Aspergilis spores (OR = 1.48, 95% CI 1.10–1.99). As noted by the authors, “…results pre- sented in this paper suggest a large overall effect of fungal exposure on child health (especially in winter). Asthma, atopy and respiratory symptoms were all significantly associated with exposure to one or more genera of fungal spores.” It appears inappropriate to rely solely on Garrett et al. (1999) (without any consideration of Garratt et al., 1998) as justification for a conclusion that formaldehyde exposure alone either causes or exacerbates of asthma or atopy. The two studies by Rumchev et al. (2002, 2004) have often been interpreted as showing a causal association between formaldehyde and asthma. Both of these case- control studies were conducted on the same population of children with the cases (N = 88) previously identified as having asthma prior to the onset of the study with