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 signs of irritation or sensitization following any of the 20 initial or challenge exposures.

In summary, the results of these laboratory studies in humans suggest that under some conditions of exposure to CCP or its components, workers may experience irritation of the upper respiratory tract or skin, and/or they may develop allergic contact dermatitis. It must be emphasized that most of these studies were negative, and the reactions observed in the positive studies were extremely rare. Furthermore, cases of allergic contact dermatitis were reported only in the earlier RIPT studies, which tested CCP types that are no longer in use; the more recent RIPT studies have detected only minor signs of skin irritation. If the Hill Top Research, Inc., guidelines are applied, then the mild irritation responses identified in some of the industry-sponsored RIPT studies would be considered Category I responses, which are defined as negative or insignificant findings, or significant findings unrelated to the test material. However, these same results do suggest that 2% or less of the population could have some type of mild reaction to CCP. Whether these mild irritation reactions would have been observed with ordinary bond paper is unclear, since these studies did not include bond paper as a control.

Hasegawa et al. 1982a. Hasegawa et al. [1982a] reported that diisopropylnaphthalenes (Kureha Micro Capsule Oil [KMC-A]) and 1-phenyl-1-xylyl-ethanes (SAS) are two classes of solvents that are used in the manufacture of CCP. They were introduced in Japan as replacements for PCBs in 1971. KMC is used by the Federal Republic of Germany and by Japan at a rate of 10,000 tons per year [Sturaro et al. 1994]. Large amounts of both materials were found in the body fat and subcutaneous fat of male JCL-SD rats 2 hr after a single oral dose of 0.1 mg/kg. The amounts increased with time until 24 hr after the dose. In the liver, the amounts were nearly the same as those in the fat after 2 hr, but they rapidly disappeared thereafter. The concentrations in blood were similar to those of the heart, kidneys, and brain. Although the ratio of isomers in the KMC-A did not change, those of the SAS 296 differed by a ratio of 3:1 for 1-phenyl-1-metaxylyl to 1-phenyl-1-orthoxylylethane, respectively. This result was attributed to differences in hepatic metabolic rates. No accumulation was found in the organs, and little accumulation was found in the fat after daily administration for 1 month.

Hasegawa et al. 1982b. Hasegawa et al. [1982b] administered 0.1g/kg body weight of KMC-A and SAS 296 to JCL-SD rats every day for 1 month. Biochemical examination revealed (1) a slight decrease in body weight and a small increase in liver weight (0.3% to 0.6%) compared with the controls; (2) disturbance of lipid metabolism in the liver (statistically significant decreases in triglycerides, glycolipids, and phospholipids) and serum (statistically significant free fatty acid twofold to threefold increases, total and free cholesterol decreases); and (3) disturbance of glucose metabolism in the liver (statistically significant decrease in glycogen and increase in pyruvate) from administration of both substances. A significant increase in alkaline phosphatase activity in the serum occurred in the case of SAS 296 administration.

Löfroth 1982. Löfroth [1982] examined a number of office materials for their potential mutagenic activity and found that none of the CCPs contained detectable amounts of mutagenic components. However, the author commented that some impurities in triaryl methanes