684 R. Golden irritation is unlikely to occur. This is why, for example, that the residential studies that report unequivocal symptoms of sensory irritation at 0.1 ppm, but lack a clean air control (e.g., Ritchie and Lehnen, 1987; Main and Hogan, 1983), do not provide a credible basis for drawing conclusions concerning airborne concentrations of formaldehyde that might be associated with sensory irritation. E.Sensory irritation effects in children and other potentially sensitive individuals Although almost all of the data on sensory irritation have been derived from studies in adults, there is limited evi- dence available to determine whether infants or children are either more or less susceptible to the irritant effects of formaldehyde than adults. Although differences between children and adults have been documented for absorp- tion, metabolism, and excretion of potentially toxic sub- stances (ILSI, 1992), such considerations are less relevant to a sensory irritant such as formaldehyde because there is no appreciable difference in the targets for irritation (i.e., eyes, nose, or throat) between children and adults. As concluded by ATSDR (1999), “Whereas there are numer- ous studies of adults occupationally exposed to formalde- hyde and exposed under acute controlled conditions, data regarding the toxicological properties of formaldehyde in children are limited. Nevertheless, the same type of effects that occur in adults are expected to occur in children…. Symptoms expected to occur in children include eye, nose, and throat irritation from exposure to airborne concen- trations between 0.4 and 3 ppm…” In an extensive review of upper respiratory tract and eye irritation effects of volatile chemicals by a group of experts, greater susceptibility among children was not mentioned (Doty et al., 2004). In another study by Meininghaus et al. (2003), sensory irritation was reported in school children. The airborne levels of several respira- tory irritants were measured (e.g., SO2, ammonia, acetic acid, formic acid, hexanal, butanal, acetaldehyde, and formaldehyde). Formaldehyde air concentrations were between 20 and 25 μg/m3 (17 and 21 ppb). Interestingly, the reported symptoms (i.e., dry sensation of the eyes, irritation of the upper respiratory tract, headache, and a rough tongue) were initially reported by adults (teachers) and it was only after those reports that several children complained about similar symptoms, suggesting either a higher sensitivity in adults than in children or pos- sibly adult responses influencing children’s responses. With respect to this latter issue, the authors concluded that psychological factors (e.g., increased attention from authorities, the presence of “experts” and sampling equipment, and a strong group behavior) may have resulted in individuals paying more attention to health effects related to sensory irritation. Also notable in these studies is that exposure involved a complex mixture of chemicals, which makes it difficult to attribute reported effects to a single chemical. Krzyzanowski et al. (1990) compared the sensitivity of children and adults to formaldehyde-induced effects on chronic respiratory symptoms and pulmonary function, reporting a greater prevalence of asthma and chronic bronchitis in children whose houses had 60–120 ppb of formaldehyde. Researchers questioned a group of 298 children (ages 6 to 15) and 613 adults using a self-admin- istered respiratory questionnaire and found no significant association between exposures in children and self- reported chronic respiratory symptoms. More than 83% of the subjects in the study lived in homes in which the 2-week average formaldehyde concentrations were less than 40 ppb. The average concentration measured was 26 ppb, with only a few homes exceeding 90 ppb, indicat- ing that the average concentrations appear to have been driven by a few outliers. Prevalence rates of chronic bron- chitis or asthma reportedly diagnosed by a physician were significantly higher when residential concentrations of formaldehyde exceeded 60 ppb, especially in the presence of tobacco smoke. Effects on peak expiratory flow rates (PEFRs) were measured in children and adults and effects assessed in conjunction with formaldehyde air concentra- tions of <40 ppb, 40–60 ppb, and > 60 ppb. Whereas effects on PEFR in adults were transient and associated mainly in smokers, effects in children decreased linearly with formaldehyde exposure and were observed at the lowest measured concentrations, with greater effects in children with asthma. However, there was no dose-response rela- tionship between the reported effects and formaldehyde concentrations. Since only formaldehyde and NO2 were measured in the air (with no effects from NO observed), 2 the assumption that all effects can be attributed to form- aldehyde alone is difficult to substantiate. It is well documented (i.e., Garrett et al., 1998, 1999; Rumchev et al., 2002, 2004) that other substances in indoor air (e.g., VOCs and fungal spores) can cause and/ or exacerbate respiratory symptoms quite apart from formaldehyde. Consequently, it is likely inappropriate to conclude that the results reported by Krzyzanowski et al. (1990) can be unequivocally attributed to formaldehyde alone in indoor air. Findings of this study (i.e., PEFRs) are questionable in view of the low levels of formalde- hyde found in the homes and at odds with controlled studies where formaldehyde was the only variable (e.g., Lang et al., 2009). In addition, as in most studies of this kind, the lack of measurements of allergens or other chemical agents that may have been present in indoor air and possibly contributed to reported symptoms is a major cofounder. Although the authors did report greater changes in PEFR in children than in adults, the use of this measure does not confirm the presence or absence of asthma or bronchitis or that formaldehyde (or something else) was responsible for this finding. This is the only study suggesting differential effects in children versus adults, hardly a convincing basis for concluding that chil- dren are more sensitive to formaldehyde. Finally, a com- prehensive evaluation by the World Health Organization (WHO, 2010) derived a value of 0.08 ppm (0.125 mg/m3) as a residential indoor air level for formaldehyde. In this evaluation, it was concluded that this value is also valid Critical Reviews in Toxicology