682 R. Golden throat irritation, and 20% to 25% for headache. Based on the controlled human exposure studies, the reported responses between 0.1 and 0.3 ppm would be difficult to distinguish from false positives (i.e., exposure to 0 ppm formaldehyde). At concentrations <0.1 ppm, less than 10% reported effects for each of these three symptoms. This study has several limitations, including (1) the par- ticipants, in order to be eligible for the study, had already complained about symptoms and were a self-selected group with a potential bias; and (2) there is no way to know what the actual formaldehyde exposure levels >0.3 ppm might have been because no such data were provided. The most substantial limitation of the study, and the one that raises questions about the reported results as they pertain to potential sensory irritation at formaldehyde levels of <0.1 ppm or between 0.1 and 0.3 ppm, is the strong likeli- hood that some unknown number of the reported effects could have been false positives. In fact, this study appears to validate the documented incidence of 20–30% false pos- itives described below at formaldehyde exposure levels of <1.0 ppm, with about 10% reporting symptoms at <0.1 ppm and 10–20% reporting symptoms at 0.1–0.3 ppm. With respect to studies conducted in residential set- tings, a NAS (2007) committee expressed skepticism about the use of such studies rather than those conducted under controlled conditions, “One of the largest studies involved nearly 2,000 residents of 397 mobile homes and 494 con- ventional homes (Ritchie and Lehnen, 1987). Participants were not selected randomly; they responded to a free testing service for formaldehyde, which was offered to individuals by the state of Minnesota when an examining physician made a written request. Thus, those recruited in the study had complained of symptoms thought to be related to airborne formaldehyde exposures” [emphasis added]. The other studies cited by CDC (2008) as the basis for conclusions on sensory irritation at a formaldehyde level of 100 ppb have similar confounding issues. 2.Controlled human exposure chamber studies Were the above types of studies the only data available (despite their obvious limitations) for deriving a weight of evidence-based concentration that would be protective for even the most sensitive individuals, such data would nec- essarily have to be relied upon. Fortunately, however, the availability of numerous controlled chamber studies using human volunteers (often including sensitive individuals and asthmatics as well as excluding insensitive individu- als such as smokers or non-responders at formaldehyde levels that produced eye irritation in other volunteers) provides a far more appropriate data set for assessing the exposure concentrations of formaldehyde required to elicit the symptoms of sensory irritation, in the absence of confounding by potential co-exposures to any other sub- stances. At least 20 published studies or critical reviews of such studies of respiratory function and/or irritation of the eyes, nose, and throat in human volunteers are avail- able that involve controlled exposure to formaldehyde, generally at concentrations up to 3 ppm or greater (e.g., Andersen, 1979; Andersen and Molhave, 1983; Bender et al., 1983; Day et al., 1984; Gorski et al., 1992; Green, 1987; Krakowiak et al., 1998; Kulle, 1993; Kulle et al., 1987; Lang et al., 2008; Pazdrak et al., 1993; Schachter, 1986, 1987; Weber-Tschopp et al., 1977; Witek, 1987). This large body of data, now relied upon by numerous regulatory and authoritative bodies worldwide, permits a more accurate assessment of formaldehyde concentrations associated or not associated with sensory irritation than workplace or residential studies. These data will be helpful in assessing whether an empirically based exposure concentration pro- tective for sensory irritation would be protective for more serious effects such as cancer and formaldehyde-induced nasal tumors for which mode-of-action data demonstrate a threshold concentration for such effects. Controlled chamber studies expose human volunteers to known concentrations of formaldehyde, with the best of these studies including clean air controls (i.e., 0 ppm formaldehyde), in order to unequivocally determine the air concentrations of formaldehyde that can reliably elicit symptoms of sensory irritation in the absence of any potential confounders. Some of these studies have also masked the odor of formaldehyde in order to eliminate odor alone as the “cause” of symptoms of sensory irrita- tion. In an extensive review, Paustenbach et al. (1997) convened a panel of experts who evaluated approxi- mately 150 studies, 52 of which were human studies with 10 of greatest relevance for establishing a concentration- response relationship for sensory irritation. As discussed in this review, “The panel concluded that for most persons, eye irritation clearly due to formaldehyde does not occur until at least 1.0 ppm. Information from controlled studies involving volunteers indicated that moderate to severe eye, nose, and throat irritation does not occur for most persons until airborne concentrations exceed 2.0–3.0 ppm.... Based on the weight of evidence from published studies, the panel found that persons exposed to 0.3 ppm for 4–6 h in cham- ber studies generally reported eye irritation at a rate no different than that observed when persons were exposed to clean air.” This conclusion is notable because all subse- quent independent reviews, which incorporate additional controlled human studies performed since Paustenbach (1997), have reached essentially identical conclusions. The Organisation for Economic Co-operation and Development Screening Information Data Set (OECD/ SIDS, 2002) concluded, “Studies in the literature have reported a variety of responses induced by exposure to gaseous formaldehyde, generally beginning in the range of 0.3 to 0.5 ppm for eye irritation, the most sensitive end- point. However, the severity of response at these levels is generally mild, and only a small portion of the population may respond.” Moderate eye, nose, and throat irritation occurs at 2 to 3 ppm. The majority of critical assessments of formaldehyde levels that would be protective for the symptoms of sensory irritation for all individuals, includ- ing those with self-reported sensitivity to formaldehyde as well as asthmatics, support a lowest effective irritant concentration of 0.3 ppm (Table 1). Critical Reviews in Toxicology