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 CCP exposure have been observed in several cross-sectional epidemiologic studies. A positive exposure-response relationship between these symptoms and CCP exposure has also been observed in those studies that examined this relationship.

The cross-sectional epidemiologic studies have several major methodologic limitations that make them difficult to interpret. One major potential source of bias in these studies is overreporting of symptoms by workers who are already aware of a potential association between CCP exposure and irritative symptoms. This form of bias is often referred to as "recall bias" and is well recognized to be a potentially important factor in epidemiologic studies in which symptoms or exposures are identified by questionnaires administered to the study subjects. Selection bias is also a major concern--particularly in studies with a low participation rate, where subjects with symptoms may have been more likely to return the questionnaires. These studies may also have been biased toward observing no effects by (1) analyzing a mix of workers with high and low potential for CCP exposures and (2) including only active workers and thus excluding workers who may have left the workforce as a result of adverse health effects related to CCP exposure.

The strongest evidence for an association between symptoms and CCP exposure comes from the studies of indoor air quality. These studies report a positive (and in several cases statistically significant) association between CCP exposure and symptoms of skin, eye, and upper respiratory tract irritation. Of the studies reviewed in this document, the indoor air quality studies are the least susceptible to recall bias because they were not conducted in workplaces where specific concerns about CCP or other indoor pollutants were heightened by previous complaints. None of these indoor air studies were designed primarily to address the CCP question, hence investigator bias is also less likely.

Other information supports the plausibility of the findings from the experimental studies in humans. The plausibility of signs and symptoms of irritation associated with CCP exposure is supported by the presence of several known irritants and allergens (e.g., formaldehyde, kerosene, phthalates, acrylates, glutaraldehyde, amines, and isocyanates) in some types of CCP and by similar effects in experimental studies of animals. For example, in seven studies of CCP and formaldehyde, nearly all exposure measurements exceeded the NIOSH REL (but not the OSHA PEL) for formaldehyde [Norbäck 1983b; Gockel et al. 1981; Hazelton Laboratories 1985; Apol and Thoburn 1986; Chovil et al. 1986; Omland et al. 1993; Zimmer and Hadwen 1993]. Finally, laboratory experiments in humans support the plausibility of the associations between irritative symptoms and exposure to CCP. Signs consistent with irritation of the skin and/or the upper respiratory tract have been noted in a few of the experimental laboratory studies in humans. However, most of these studies failed to demonstrate any effects or showed extremely mild reactions to CCP exposure. Inconsistencies in the findings of these studies might easily be explained by differences in study design and particularly by differences in the types of CCP tested.

Allergic Contact Dermatitis

Several authors have reported cases of allergic contact dermatitis that appear to have been associated with CCP or its components [Marks 1981; Kannerva et al. 1990a,b, 1993; Shehade 1987]. Development of sensitization to CCP or its components was also reported in a few persons in several industry-sponsored repeated insult patch test (RIPT) studies (Report 77-512-70 and Supplemental Report 79-512b-70, Report 77-896-71, and Report Rh