79-0085-73, all from Hill Top Research, Inc.; and Project SH-72-4, dated April 18, 1972, performed by the Shelanski Holding Company, Conshohocken, Pennsylvania, for Monsanto Co., St. Louis, Missouri). In 8 of 217 test materials, study investigators indicated that skin sensitization occurred in some human subjects. However, these studies were mostly judged to be negative for irritation by the investigators. Thus in a small proportion of the population, CCP or its components appear capable of inducing cell-mediated (type IV) immune response and allergic contact dermatitis, particularly under the intensive exposures associated with RIPT protocols. Cases of allergic contact dermatitis were reported only in RIPT studies from the 1970s that were submitted to the 1987 NIOSH docket; no cases were reported in the studies submitted to the 1997 docket. This fact indicates that the CCP component(s) responsible for the allergic contact dermatitis observed in the early studies may have been removed from current formulations of CCP.
Systemic Reactions
Three patients with systemic reactions clinically suggestive of mast cell and/or basophil degranulation after cutaneous challenge with CCP or its components have been reported in two published case reports [Marks et al. 1984; LaMarte 1988]. These reports suggest that some CCPs or their components can induce reactions clinically compatible with those caused by mast cell and/or basophil mediator release. Immunologic sensitization was not adequately evaluated in these studies, and thus it is unclear whether an immunologic mechanism underlies these reactions. However, no additional reports were located in the peer-reviewed literature over the last 12 years. Thus, even if the reported reactions were referable to CCP exposure, systemic reactions of this type appear to be exceedingly rare. Furthermore, the relevance of these reports to current CCP exposures is uncertain.
Conclusions
On the basis of a NIOSH review of the scientific literature and information submitted in response to its 1987 and 1997 Federal Register notices, NIOSH concludes the following:
- The weight of the evidence supports the conclusion that exposure to certain types of CCP or its components has, under some conditions, resulted in symptoms of irritation of the skin and of the mucosal membranes of the eyes and upper respiratory tract.
- This conclusion is based primarily on interpretation of the evidence from the epidemiologic studies. Although the magnitude of the effects observed in these studies was only weak to moderate, these studies were reasonably consistent in reporting an association and evidence of an exposure-response relationship between CCP exposure and irritative symptoms of the eyes, skin, and upper respiratory tract. The plausibility of the epidemiologic evidence is supported by the presence of known irritants in some types of CCP, toxicologic studies that demonstrate mild irritation in laboratory animals exposed to CCP, and the evidence for respiratory and skin irritation in some of the experimental laboratory studies in humans. Some of the epidemiologic studies may have been biased, particularly by overreporting from study subjects who were already concerned about the potential effects of CCP exposure (i.e., recall bias). However, it is unlikely that recall bias could explain the associations observed between CCP exposure and irritative symptoms of the eyes, skin, and upper respiratory tract in the indoor air quality studies, since these studies were not conducted in an atmosphere of concern regarding the health effects of CCP.
