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 1987]. Development of sensitization to CCP or its components was also reported in a few persons in several industry-sponsored RIPT studies (Report 77–512–70 and Supplemental Report 79–512b–70, Report 77–896–71, and Report 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 shown in Table 4–12, 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 the more recent formulations of CCP.

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]. One patient challenged by CCP handling became symptomatic approximately 15 to 20 min after exposure and experienced swelling of the exposed hand, hives on the neck, changes in both the inspiratory and expiratory limbs of the flow-volume loop (suggesting upper airways obstruction), and elevated circulating levels of several arachidonic acid metabolites. Skin-prick testing with CCP dust was reported to be negative [Marks et al. 1984]. One patient who was challenged by rubbing 1% alkylphenol novolac resin dispersion onto the forearm became symptomatic approximately 15 min after exposure and developed hoarseness, wheezing, and angioedema of both arms. A subsequent challenge with this material was followed by hoarseness, wheezing, and angioedema at the challenge site. Video endoscopy of the larynx was interpreted as showing diffuse swelling and marked edema of the true vocal cords. Plasma histamine levels obtained at the onset and peak of symptoms were sixfold higher than the prechallenge level [LaMarte 1988]. Finally, one patient who was challenged by rubbing 1% alkylphenol novolac resin onto one arm was reported to have angioedema of the arm and hoarseness 30 min after challenge [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.

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 