significant, the authors noted that the higher number of nickel reactions in the exposed group may indicate a higher prevalence of atopic workers in that group and thus a potential bias in the study. No increased skin dryness or desiccation was noted in the exposed or comparison groups. Possible shortcomings of this otherwise well-designed study are that (1) the matched comparison workers were not matched for the amount of ordinary paper they handled, and (2) the matching does not appear to have been considered in the analysis of the data. Thus the study results may be potentially confounded by the matching factors and by ordinary paper exposure. On the other hand, the strength of the association (P<0.007) and the evidence of an exposure-response relationship (P=0.049) support an association of some types of CCP with pruritus.
Apol and Thoborn 1986. See Section 4.2.1 for a discussion of this study.
4.2.4 Laboratory Studies in Humans
This section reviews studies that used some form of experimental testing in humans (such as patch or prick tests) under controlled laboratory conditions to assess the potential health effects of exposure to CCP or its components. These studies are distinct from the laboratory studies performed in some of the case studies and cross-sectional studies reviewed earlier in this chapter (see Sections 4.2.1 and 4.2.3), which generally involved a few cases from a specific company and did not employ a rigorous experimental design. In addition to the peer-reviewed literature, this section examines unpublished experimental studies that were usually sponsored by the U.S. manufacturers of CCP and were submitted to the NIOSH docket.
The experimental nature of laboratory studies offers advantages over the observational studies described in earlier sections. These studies do not have the potential for confounding or recall bias that the observational studies had. However, laboratory studies also have limitations that undermine their usefulness for judging the causal relationship between CCP exposure and health effects. First, these studies are largely limited to the inclusion of healthy volunteers. A consequence of this approach is that persons with a history of allergy or irritation reaction might be less likely to volunteer than those with no symptoms, thus creating selection bias. Second, it is unclear whether the exposures in laboratory studies are representative of those actually experienced by workers in the field. Third, most of the laboratory studies did not include ordinary paper as a control. Thus it is not possible to determine whether the effects observed in some studies result from chemical components of CCP or from the paper itself.
4.2.4.1 Peer-Reviewed Literature Studies
Table 4-11 summarizes the three experimental studies in humans that have appeared in the peer-reviewed literature. These studies are discussed below.
Nilzen 1975. At the request of a CCP manufacturer, Nilzen [1975] of Sweden conducted provocative tests (including patch, prick, eye, and nose irritation tests with water extracts) and vapor inhalation studies with crushed CCP and ordinary bond paper. The patch tests in eight subjects were negative, but prick tests resulted in an unspecified number of weak and medium-strong reactions to both CCP and ordinary bond paper. Two subjects were tested by inhalation of vapors from CCP or bond paper, and both resulted in irritation; however, the CCP caused a greater reaction. The author concluded that (1) certain persons with a history of allergy or irritative reactions may react to CCP as well as to ordinary bond paper and a variety of other materials and (2) despite evidence of
