asthma or its exacerbation. In exploring possible mecha- nisms for formaldehyde-induced bronchoconstriction, Thompson and Grafstrom (2008) noted that “The poten- tial for formaldehyde to provoke asthma, hypersensitivity, and airway constriction in adults and children has received extensive attention over the years, yet data regarding these effects remain equivocal.” Although the hypothetical mechanism proposed by those authors may or may not lead to a better understanding of whether formaldehyde plays a causative role in asthma-related bronchoconstric- tion, at present the evidence suggests that asthma is nei- ther caused nor exacerbated by low-level exposure (i.e., less than 1–2 ppm) (Noisel et al., 2007). Additional mech- anistic support for why asthmatics are not more sensitive to formaldehyde at environmentally relevant levels is the well-documented effective scrubbing of low levels of this highly water-soluble gas in the upper airways below 3 ppm (i.e., Schlosser et al., 2003; Kimbell et al., 1993, 2001; Overton et al., 2001; Garcia et al., 2009). As a result, little formaldehyde at these concentrations reaches the mid to lower airways where an asthmatic reaction may be triggered. The lack of sensitivity of asthmatics at these lower air levels in controlled chamber studies is consis- tent with expected patterns of absorption in the upper airways. Although formaldehyde is clearly a sensory irritant at sufficient concentrations with different individual sensitivities, its potential to cause or exacerbate asthma is far less certain particularly at low exposure levels (<1–2 ppm). There are no studies in which exposure to formaldehyde alone has been shown to cause or exac- erbate this disease. Instead, studies that have reported this effect are all confounded, to an unknown extent, by simultaneous co-exposures to other chemicals, many of which themselves have been associated with exacerbat- ing asthmatic symptoms. G.Data from which to derive an indoor air formaldehyde concentration protective for sensory irritation 1.Key studies or evaluations In 2007, testing was conducted to determine formalde- hyde levels in unoccupied FEMA temporary housing units in order to assess the most effective way to ventilate these units and to identify a health-protective indoor air concentration limit for formaldehyde (ATSDR, 2007b). A target indoor air concentration of 0.3 ppm formalde- hyde was selected by ATSDR because this level was “… below the level of concern for sensitive individuals of 369 ug/m3 (0.3 ppm).” This empirically derived concentra- tion (0.3 ppm) was taken from ATSDR documents and, as shown in Table 1, is the same concentration selected by the National Academy of Sciences (NAS, 2007) (and numerous other entities) as a continuous exposure guid- ance level (CEGL) for formaldehyde in submarines. As noted in the NAS publication, “Reported symptoms of eye and mucous membrane irritation at that concentration [i.e., 0.3 ppm] were not increased above control conditions © 2011 Informa Healthcare USA, Inc. Indoor air exposure limit for formaldehyde 687 in controlled chamber studies.” In establishing the 0.3 ppm value, both ATSDR and NAS relied on extensive human volunteer exposure data (i.e., chamber studies) as the basis for their identical determinations. The conclusion that an exposure limit of 0.3ppm formaldehyde in indoor air is conservative and health protective is fully supported by recent independent evaluations. For example, in an evaluation of the human data on formaldehyde a Dutch review noted that “…it can be concluded that minimal/mild/slight eye irritation starts at levels of 1.0 ppm formaldehyde and higher.” The same review also concluded that nasal and throat irrita- tion start at formaldehyde levels of 2.0 ppm and 3.0 ppm, respectively (TNO Nutrition and Food Research, 2003). In deriving Acute Exposure Guideline Levels (AEGLs), US EPA (2004) selected 0.9 ppm as the AEGL for an 8-hour exposure, noting that “At 0.35 to 0.9 ppm, the subjects sub- jective eye irritation responses ranged from none to slight, the same as their responses to clean air.” As summarized in Table 1, authoritative and comprehensive reviews recog- nize 0.3 ppm as a prudent level of exposure to formalde- hyde in indoor air, with most evaluations of the empirical evidence clustering at this value. In fact, based on human chamber studies, 0.3 ppm essentially incorporates an additional “margin of safety” of 3 because 1.0 ppm is the lowest formaldehyde exposure level for eye irritation not confounded by the likelihood of false-positive reports. In a comprehensive review of formaldehyde-induced sensory irritation, Arts et al. (2006) evaluated 10 of the controlled human studies and the subjectively mea- sured sensory irritation threshold levels at which effects occurred. On a normalized scale (i.e., response severity index from all studies standardized as 0 = none, 1 = slight, 2 = moderate, 3 = severe) in which all available studies were similarly evaluated, mild/slight eye irritation was observed at formaldehyde levels ≥1 ppm, and respiratory tract irritation at levels ≥2 ppm. In rating studies in which sensory irritation was sufficiently described to incorpo- rate evaluation by the benchmark dose methodology, “...it was estimated that at a level of 1 ppm, only 9.5 % of healthy volunteers experience ‘moderate’ (i.e., annoying) eye irritation (95% upper confidence limit).” It was also concluded that an important factor modulating the per- ception of irritation and health symptoms most likely includes the perception of odor intensity, particularly since in several studies the 0 ppm control condition was missing. This is a critical consideration because, as noted by Arts et al. (2006), “In some of the studies measuring subjective irritation in which a 0-ppm control concentra- tion was included, a response percentage of eye irritation of up to about, 20% was found at 0 ppm. Also, nasal and/ or throat irritation up to almost 30% was reported in the absence of formaldehyde…therefore, response percentages of about, 20–30%, if at all responses, should be interpreted with caution, especially in those studies in which a 0-ppm control condition is missing.” Similarly, Noisel et al. (2007) conducted an assessment of the exposure-response relationships for the incidence