The Sapphire Group 3 Bethesda Metro Center, Suite 700 Bethesda, MD 20814
In their article on exposure to self-copying paper, Jaakkola and Jaakkola (1) present a variation on the theme of circular epidemiology (2
). They use data designed for another purpose to investigate an unproven hypothesis, and their findings do not add to the body of knowledge because they fail to control for the most relevant variable.
We have recently become familiar with evidence pertaining to the potential health impact of carbonless copy paper, one form of self-copying paper. Case reports and biased questionnaire studies abound, but almost no studies have included matched controls and verified, quantified exposures. We are convinced that carbonless copy paper does not cause irritation or any other adverse health impact.
Following early investigations in which participants were asked leading questions, studies of "sick building syndrome" came into vogue in the mid-1980s. These studies considered many factors associated with enclosed buildings and concluded that generic symptoms (e.g., skin and mucous membrane irritation) were associated with indoor air characteristics such as low ventilation rate (7
), low humidity (
11
), high temperature (6
, 10
, 12
), and lack of fresh air exchange (4
, 13
, 14
).
While Jaakkola and Jaakkola (1) report on a study of sick building syndrome carried out in 41 buildings in Finland in 1991, its relevance to the use of carbonless copy paper in the United States today is unclear. European carbonless copy paper employs active clay as the color developer; US carbonless copy paper uses resin-based developer. The study was designed to examine the role of building ventilation in relation to symptoms associated with sick building syndrome; questions on the use of office equipment were ancillary. The questionnaire asked, "Do you use self-copying paper in your work?" No time frame was specified, so a positive response could be elicited by infrequent use of as little as a sheet or two of self-copying paper. The authors stated that most self-copying paper in their study was carbonless copy paper, but no data support this statement. Other types of self-copying paper include forms using carbon backing, carbon paper, physical revelation paper, and thermal paper.
Two earlier reports from this study were published (15, 16
). The earliest paper (15
) presented odds ratios in relation to type of ventilation system (e.g., mechanical ventilation, air conditioning with or without humidification) and included 126 odds ratios, of which 12 were statistically significant (range, 1.62.7). The second paper (16
) calculated odds ratios for categories of ventilation rate (medium vs. very low, low, and high) and included 39 odds ratios, of which 16 were significant (range, 3.041.0). The current report (1
) used the same data but calculated odds ratios for use of self-copying paper while controlling for type of ventilation system. Here, 15 of the 21 odds ratios were statistically significant (range, 1.31.8). The current paper and the first published report by Jaakkola and Miettinen (15
) included 2,678 subjects, while the second paper published by Jaakkola and Miettinen (16
) reported on a subset of 399 subjects for whom data on ventilation rate were available.
It is evident that ventilation rate would be more informative than type of ventilation system as the control variable, since the second paper (16) considered ventilation rate and found larger odds ratios and a larger proportion of significant odds ratios. It is difficult to know what importance to attach to the odds ratios in the current paper (1
) when ventilation rate is unaccounted for. For example, in the second paper (16
), the odds ratio associated with eye symptoms and a very low ventilation rate was 5.6, while the odds ratio for eye symptoms and a high ventilation rate was 4.3. The odds ratio of 1.6 associated with eye symptoms and use of self-copying paper in the current report (1
) was not controlled for ventilation rate and therefore does not offer evidence of an association between eye symptoms and self-copying paper use. For skin symptoms and self-copying paper use, the odds ratio of 1.7 in the current report (1
) is meaningless in light of the odds ratio of 41.0 for skin symptoms and a very low ventilation rate in the second report (16
). Similar arguments can be made for the other odds ratios in the current report.
Because Jaakkola and Jaakkola did not control for ventilation rate, the Finnish data do not demonstrate an association between use of self-copying paper and any symptoms. The paper is merely an example of circular epidemiologynamely, if one repeats a hypothesis often enough it begins to be believed, even though no data exist to support it.
REFERENCES
Finnish Institute of Occupational Helath Topeliuksenkatu 41 aA FIN-00250 Helsinki, Finland
Schools of Hygiene and Public Health Johns Hopkins University Johns Hopkins University Baltimore, MD 21205
We thank Graves and Tardiff (1) for their letter. They made some statements about our article (2
) that we would like to correct. The aim of the population-based Helsinki Office Environment Study, which included 2,678 workers from randomly selected office buildings, was to evaluate potential adverse health effects related to the office environment. Use of office equipment and supplies was one of the main concerns suggested by previous studies (3
8
) and was not just an ancillary issue. The questionnaire used in our study was carefully developed and tested to include potentially relevant factors in the office environment. It was an important instrument in the study, in addition to the measurements performed in the offices. To avoid selection bias that might be related to studies including "problem" buildings only, we included a random sample of office buildings in the Helsinki metropolitan area.
Carbonless copy papers include different solvents, color formers, capsule walls, and coreactive surfaces, and any of these ingredients could cause allergic or irritative symptoms (9). Some of them can even cause toxic reactions. Several chemicals have been identified as specific causes of symptoms in case reports, but the exact mechanisms are not well understood (2
, 9
). We are not able to judge whether the mentioned differences between European and US carbonless copy paper are relevant to health effects, nor do Graves and Tardiff present any references on this topic. It is possible that mixtures of chemicals found in carbonless copy paper are more relevant than single chemicals. It would be very interesting to test hypotheses related to specific mechanismsfor example, in challenge studiesif the industry were to inform us about the compounds and mixtures contained in these products.
Our study was performed in 1991, when use of carbon paper was already uncommon in Finland. Use of thermal paper is still uncommon in office environments, and it is used mainly in faxes and shopping receipts. Thus, it is likely that most of the self-copying paper used by the participants in our study was carbonless copy paper. In any case, with regard to inference of the results, we point out that any nondifferential error in classifying other copy papers as carbonless would lead to an underestimation of the effect of carbonless copy paper exposure.
The main criticism of Graves and Tardiff is actually based on confusion about the concept of confounding. A confounding factor is a determinant (or risk factor) of the studied outcome that is related to the exposure of interest but is not intermediate in the causal chain (10). Ventilation rate is not a direct determinant of the outcomes studied, and there is no evidence of an association between ventilation rate and use of carbonless copy paper. This means that lack of control for ventilation rate cannot explain the observed relations between use of self-copying paper and sick building syndrome and chronic respiratory symptoms. Ventilation decreases the concentrations of indoor pollutants; thus, with a given emission rate, the actual airborne exposure is lower the higher the ventilation rate. Therefore, the health risks may be even stronger than reported in our study in offices with a low ventilation rate. This question is important in considering how to prevent sick building syndrome and chronic respiratory symptoms related to the use of self-copying paper, and it should be studied further.
REFERENCES