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 ordinary bond paper. Nilzen [1975] also reported symptoms consistent with nasal irritation in subjects exposed to vapors from CCP or bond paper, but the CCP caused a stronger reaction. Another study measuring the effects of CCP on nasal passages reported signs consistent with nasal irritation and congestion [Morgan and Camp 1986; Koenig 1988]. In an industry-sponsored study, a high percentage of subjects (40%) demonstrated irritation of the eyes, skin, or nose when they used scissors to cut one particular type of CCP (Hill Top Research, Inc., Report 83–0965–70), but not when they cut bond paper. Signs of dermal irritation (e.g. Hill Top Research, Inc., Report 79–0085–73) were observed in some of the RIPT studies that were submitted to the 1987 docket. However, the use of the products tested in these studies has generally been discontinued. Only very mild signs of skin irritation were observed among subjects in the more recent RIPT studies that tested CCP materials in current use and that were submitted to the NIOSH docket in 1997. Generally less than 2% of subjects demonstrated very mild skin irritation in these studies, but higher percentages (e.g., >10%) were reported for some of the materials tested in two of the more recent studies submitted to the docket (Hill Top Research, Inc., 1998 and 1999). However, these two studies were not considered by the investigators to be positive for irritation. These experimental studies are not subject to the potential recall bias of the epidemiologic studies, since they used objective tests. Also, it is very unlikely that the positive findings in some of these studies could be explained by other forms of biases or chance. The inconsistency between the findings in these studies may be explained by differences in the types of CCP tested or other differences in study design. It is unclear how relevant these experimental models are, since the exposure from patch testing is quite different from exposures among workers who use CCP in offices and elsewhere. These studies also have the potential for a negative selection bias, since they generally involved healthy volunteers and could thus have excluded sensitive persons.

Reasoning by analogy refers to making an analogy with the known health effects for a similar exposure. For example, the fact that a drug has characteristics similar to Thalidomide (a known teratogen) provides support for a causal relationship between this drug and birth defects. No useful analogies exist for CCP; thus this criterion is not useful for judging causality in this case.

In summary, the Hill criteria for consistency, specificity, temporality, biological gradient (dose-response), biological plausibility, and experimental evidence support a casual association between CCP exposure and irritative symptoms of the skin, eyes, and upper respiratory tract. Because the associations observed in the epidemiologic studies were generally weak to moderate, the evidence does not fully satisfy the criterion for the strength of association. Although not all of the criteria are fully met, Hill [1977] points out that none of the criteria can provide absolute proof of a cause-and-effect relationship, and none should be used as an absolute requirement for proof of a cause-and-effect relationship. Furthermore, not all of these criteria are equally important. The dose-response relationship observed and the experimental evidence reported for some CCP exposures and irritative symptoms of the eyes, skin, and upper respiratory tract provide the strongest evidence for a causal association.

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