NIOSH HAZARD REVIEW Carbonless Copy Paper U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Centers for Disease Control and Prevention National Institute for Occupational Safety and Health NIOSH HAZARD REVIEW Carbonless Copy Paper U.S. Department of Health and Human Services Public Health Service § Centers for Disease Control and Prevention National Institute for Occupational Safety and Health December 2000 Ordering Information To receive documents or other information about occupational safety and health topics, contact the National Institute for Occupational Safety and Health (NIOSH) at NIOSH—Publications Dissemination 4676 Columbia Parkway Cincinnati, OH 45226–1998 Telephone: 1–800–35–NIOSH (1–800–356–4674) Fax: 1–513–533–8573 E-mail: [email protected] or visit the NIOSH Web site at www.cdc.gov/niosh This document is in the public domain and may be freely copied or reprinted. Disclaimer: Mention of any company or product does not constitute endorsement by NIOSH. DHHS (NIOSH) Publication No. 2001–107 ii Foreword n response to its mandate to provide a safe and healthful workplace for working women and Imen, the National Institute for Occupational Safety and Health (NIOSH) critically evaluates the scientific data on potentially hazardous occupational exposures or work conditions and recom- mends measures for minimizing the risk from the hazard. Millions of workers routinely handle carbonless copy paper (CCP) forms each day. Reports of possible health effects from at least 12 countries have been published in the scientific literature. This document presents a review of the health effects of CCP. When investigating the relationship between occupational exposures and ad- verse health effects, NIOSH generally prefers to use the published literature; but some unpublished sources were used in this review because the published literature was limited. Also considered as part of this review were more than 14,000 pages of material submitted to NIOSH in response to Federal Register notices requesting information about CCP. Such a comprehensive review should help address issues of CCP exposure in the U.S. workforce. Lawrence J. Fine, M.D., Dr.P.H. Acting Director, National Institute for Occupational Safety and Health Centers for Disease Control and Prevention iii Executive Summary n 1987, the Occupational Safety and Health variations from different suppliers), physical IAdministration (OSHA) requested that the form of the paper (rolls versus sheets), and fi- National Institute for Occupational Safety and nal form of the product (i.e., bound with adhe- Health (NIOSH) investigate the validity of re- sives). Thus the product known as CCP is not a ported adverse health effects in workers occu- single product but includes thousands of differ- pationally exposed to chemicals contained in ent and often unique products [Mead Corpora- or released from carbonless copy paper (CCP). tion 1997]. This fact needs to be considered Because of limited published information, when interpreting the findings from the scien- NIOSH issued a Federal Register notice solic- tific literature. iting information about possible adverse health effects from CCP exposure [52 Fed. Reg.* About 10 years after the introduction of CCP, 22534 (1987)]. On the basis of information medical complaints began to be reported by available at that time, no strong conclusion office workers [North Carolina Medical Jour- could be reached concerning a consistent link nal 1982; Magnusson 1974; Göthe et al. 1981; between CCP and major health effects. Be- Buring and Hennekens 1991]. Since 1965, tween 1987 and 1997, additional reports in- various health effects associated with expo- volving health problems potentially related to sure to CCP have been reported in the litera- CCP were identified. Therefore, in 1997 ture appearing from Denmark, Finland, NIOSH issued a second Federal Register no- England, Sweden, Germany, the Netherlands, tice soliciting new information [62 Fed. Reg. France, Italy, Belgium, Japan, Norway, and the 8023 (1997)]. This report contains a review of United States. the published literature on CCP and the sub- NIOSH has reviewed the published and unpub- missions to the NIOSH docket from the two lished literature on CCP. The following para- Federal Register notices. graphs summarize the findings from this review regarding the primary health effects associated with CCP exposure. CCP was introduced in 1954 by the National Cash Register Company as no-carbon-required (NCR) paper—an alternative to separate Irritation of the Skin, Eyes, and sheets of carbon paper [Sandberg 1955; Green Upper Respiratory Tract 1955; Miller and Phillips 1972; Calnan 1979; The most common findings from the human Buring and Hennekens 1991]. A given CCP studies are symptoms consistent with irrita- can vary greatly as to its constituents, weight tion of the skin, eyes, and upper respiratory and types of paper coatings, paper color, dye system following exposure to some types of colors and combinations of dyes used on coat- CCP. These symptoms have also been de- ings, solvents and solvent mixtures (including scribed in numerous case reports and case se- ries of persons exposed to CCP, and *Federal Register. See Fed. Reg. in references. associations between these symptoms and iv CCP exposure have been observed in several primarily to address the CCP question, hence cross-sectional epidemiologic studies. A posi- investigator bias is also less likely. tive exposure-response relationship between these symptoms and CCP exposure has also Other information supports the plausibility of been observed in those studies that examined the findings from the experimental studies in this relationship. humans. The plausibility of signs and symp- toms of irritation associated with CCP expo- The cross-sectional epidemiologic studies sure is supported by the presence of several have several major methodologic limitations known irritants and allergens (e.g., formalde- that make them difficult to interpret. One ma- hyde, kerosene, phthalates, acrylates, jor potential source of bias in these studies is glutaraldehyde, amines, and isocyanates) in overreporting of symptoms by workers who some types of CCP and by similar effects in are already aware of a potential association be- experimental studies of animals. For example, tween CCP exposure and irritative symptoms. in seven studies of CCP and formaldehyde, This form of bias is often referred to as “recall nearly all exposure measurements exceeded bias” and is well recognized to be a potentially the NIOSH REL (but not the OSHA PEL) for important factor in epidemiologic studies in formaldehyde [Norbäck 1983b; Gockel et al. which symptoms or exposures are identified by 1981; Hazelton Laboratories 1985; Apol and questionnaires administered to the study sub- Thoburn 1986; Chovil et al. 1986; Omland et jects. Selection bias is also a major con- al. 1993; Zimmer and Hadwen 1993]. Finally, cern—particularly in studies with a low laboratory experiments in humans support the participation rate, where subjects with symp- plausibility of the associations between irrita- toms may have been more likely to return the tive symptoms and exposure to CCP. Signs con- questionnaires. These studies may also have sistent with irritation of the skin and/or the been biased toward observing no effects by upper respiratory tract have been noted in a (1) analyzing a mix of workers with high and few of the experimental laboratory studies in low potential for CCP exposures and (2) in- humans. However, most of these studies failed cluding only active workers and thus excluding to demonstrate any effects or showed extremely workers who may have left the workforce as a mild reactions to CCP exposure. Inconsis- result of adverse health effects related to CCP tencies in the findings of these studies might exposure. easily be explained by differences in study de- sign and particularly by differences in the types The strongest evidence for an association be- of CCP tested. tween symptoms and CCP exposure comes from the studies of indoor air quality. These Allergic Contact Dermatitis studies report a positive (and in several cases statistically significant) association between Several authors have reported cases of allergic CCP exposure and symptoms of skin, eye, and contact dermatitis that appear to have been as- upper respiratory tract irritation. Of the stud- sociated with CCP or its components [Marks ies reviewed in this document, the indoor air 1981; Kannerva et al. 1990a,b, 1993; Shehade quality studies are the least susceptible to re- 1987]. Development of sensitization to CCP or call bias because they were not conducted in its components was also reported in a few per- workplaces where specific concerns about sons in several industry-sponsored repeated in- CCP or other indoor pollutants were sult patch test (RIPT) studies (Report heightened by previous complaints. None of 77–512–70 and Supplemental Report these indoor air studies were designed 79–512b–70, Report 77–896–71, and Report v 79–0085–73, all from Hill Top Research, Inc.; Conclusions and Project SH–72–4, dated April 18, 1972, On the basis of a NIOSH review of the scien- performed by the Shelanski Holding Company, tific literature and information submitted in re- Conshohocken, Pennsylvania, for Monsanto Co., sponse to its 1987 and 1997 Federal Register St. Louis, Missouri). In 8 of 217 test materials, notices, NIOSH concludes the following: study investigators indicated that skin sensiti- zation occurred in some human subjects.