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 (3) specificity, (4) relationship in time (temporality), (5) biological gradient, (6) biological plausibility, (7) coherence, (8) experimental evidence, and (9) reasoning by analogy. The following sections describe these criteria and use them to evaluate the reported associations between CCP exposure and irritation of the skin, eyes, nose, and upper respiratory tract.

Associations that are large in magnitude are considered more likely to be causal, since they are less likely to be explained by confounding or other forms of bias. In the cross-sectional studies, weak to moderate associations were observed between CCP exposure and irritation of the skin, eyes, and upper respiratory tract. The odds ratios (ORs) reported in the cross-sectional studies summarized in Table 5–2 were approximately between 1.1 (e.g., Zweers [1992]) and 2.3 (e.g., Mendell [1991]). The strength of association for rate (or odds) ratios that are 1.2 to 1.5 and 1.5 to 3.0 has been interpreted as being weak and moderate, respectively (see Monson [1980], p. 94). It should be recognized that the size of the odds ratios are limited by the relatively high background rates of the symptoms studied. Many of the other cross-sectional studies (i.e., non-indoor air studies) did not include an unexposed population, and thus it is difficult to judge the strength of association in these studies. It is noteworthy that the prevalence of symptoms among workers with extremely high CCP exposures (i.e., $1,000 sheets/day) was between 92% and 100% in two of the non-indoor air cross-sectional studies (Table 5–1), which suggests a strong association among highly exposed workers.

Consistency refers to the repeated observation of similar findings in numerous study settings. The case studies and case series reports are consistent insofar as they report similar symptoms involving the skin and mucosal membranes of the eyes and upper respiratory tract. However, this apparent consistency might be partly a reporting bias that occurs because investigators have read previous case reports and are more likely to report findings that are similar to those previous reports. Perhaps more convincing is the fact that the cross-sectional epidemiologic studies were generally consistent (see Table 4–3) in associating skin, eye, and upper respiratory symptoms with exposure to CCP. Associations of CCP with other symptoms such as headache and fatigue have not been consistently observed in these studies. Overall, the epidemiologic studies are judged to be relatively consistent in reporting irritative symptoms of the skin, eyes, and upper respiratory tract.

Specificity requires that an exposure be associated with a single specific effect. Furthermore, if a disease has no other major risk factors (e.g., asbestos and mesothelioma), the association is often very credible and the studies are the least susceptible to recall bias. The irritative symptoms of the eyes, skin, and upper respiratory tract reported in CCP studies are common effects with many risk factors. Ocular and upper respiratory tract irritative symptoms in particular can be triggered by many exposures encountered in the indoor environment and are quite prevalent in many office buildings. Thus the irritative symptoms of the eyes, skin, and upper respiratory tract that have been associated with CCP exposure are not specific to CCP. On the other hand, the studies have been relatively consistent in reporting an association between CCP exposure and irritative symptoms of the eyes, skin, and upper respiratory tract. These symptoms commonly occur together with exposures