VOL.: 65 (1996) (p. 33)
For definition of Groups, see Preamble Evaluation.
5.1 Exposure data
Printing inks are mixtures of three main types of ingredients: pigments, vehicles and additives. Pigments used in printing inks include both inorganic pigments such as carbon black and titanium dioxide and organic pigments, which are frequently dyes rendered insoluble by complexing with a metal ion. Most organic pigments are prepared from azo, anthraquinone and triarylmethane dyes, and phthalocyanines.
There are five main printing processes, and inks are designed for the specific process. Lithography and letterpress are collectively known as the 'paste ink' processes and use inks that are essentially non-volatile at normal temperatures. Flexography and gravure are known as the 'liquid ink' processes and are based upon volatile solvents that evaporate readily at room temperatures. Screen printing uses inks that fall between the other two groups.
Choice of the vehicle (solvent with resins) for a printing ink depends on the printing process, how the ink will be dried, and the substrate on which the image is to be printed. In lithography and letterpress, where inks are dried by absorption and oxidation, vehicles are generally mixtures of mineral and vegetable oils and resins. Flexographic inks, which are designed to dry quickly by evaporation, can be either water-based or based on organic solvents (such as ethanol, ethyl acetate, n-propanol or isopropanol) with a wide variety of resins. Vehicles for gravure inks, which also dry by evaporation, may also contain aromatic or aliphatic hydrocarbons and ketones as solvents. Inks for screen printing use organic solvents that are somewhat less volatile than those used for flexography or gravure (higher glycol ethers and aromatic and aliphatic hydrocarbons). Additives in inks include driers, waxes and plasticizers.
Ultraviolet radiation-cured inks, commonly based on acrylates, are used in all of the printing processes to varying degrees.
The manufacture of inks consists of dissolving or dispersing resins in organic solvents or oils to produce the vehicle (varnish), mixing and dispersing the pigment or dye into the vehicle, introduction of any additives and packaging. Some or all of these stages may be done manually or automatically in a batch process or as a continuous process.
During the manufacture of printing inks, exposure to pigments, vehicles and additives can occur through inhalation or skin contact during mixing and dispersion and during clean-up of mixers. Exposures are higher with liquid inks than with paste inks. During newspaper printing by letterpress or lithography, the major exposure is to ink mist. Rotary letterpress was the dominant process for the production of newspapers until the 1970s. It has now been largely replaced by web offset litho, in which exposures to ink mist are considerably lower than for letterpress. In other lithographic and letterpress printing, the major exposure is to hydrocarbon-based cleaning solvents and isopropanol from damping solutions. In flexographic, gravure and screen printing, exposures are mainly to organic solvents. Historically, some workers in both ink manufacture and printing were exposed to much higher levels of lead, polycyclic aromatic hydrocarbons and benzene than today, and the development and use of modern control technologies have made possible the marked reduction in solvent and ink mist exposures.
5.2 Human carcinogenicity data
A large volume of epidemiological data deals with potential cancer risks in printing processes. Because of the presence of a fairly large number of adequate cohort and case-control studies, it was considered that there was no marginal benefit in considering further the descriptive studies based on simple tabulations of death certificate causes of death and mentions of occupation. In any case, these latter studies did not provide clear patterns of results.
The evaluation of results of case-control and cohort studies, in particular those regarding relatively rare neoplasms, was hampered by the possibility of reporting or publication bias. A second problem was the poor specificity of exposure information. While most studies were based on crude designations of the exposure variable, a few, most notably some of the cohort studies, did describe risks for subgroups of the printing industry that are more homogenous in exposure circumstances. The Working Group tried to identify such subgroup studies with presumably more well-defined common exposure circumstances. In a small number of studies, there was an explicit attempt to identify a group of workers exposed to printing inks. This, like the designation of exposure on the basis of the job or industry title, is of poor specificity. Further, most of these were in the context of community-based case-control studies, and the attribution of exposure was based on job-exposure matrices, which do not discriminate among subsectors of the printing industry.
A third problem was that most of the cohort and record-linkage studies had no information on some important counfounders, notably cigarette smoking. It has previously been shown that confounding by smoking is unlikely to distort the relative risk estimate between occupation titles and lung cancer by more than 30%. For other sites that are affected by smoking, the maximal bias is likely to be even lower. The Working Group considered these possible biases when interpreting results.
Apart from cancers of the lung, oropharynx, urinary bladder and kidney and leukaemia, which are presented below, the Working Group considered that the findings are not strong or consistent enough to be evaluated.
Lung cancer
Ten community-based case-control studies examined the relationship between lung cancer and occupation and reported results regarding printing industry and/or printing related occupations. Increased relative risks were found in eight studies; smoking was controlled for in six of them and the smoking-adjusted relative risks for 'printing occupations' ranged from 1.1 to 3.3. Two studies reported findings for exposure to printing inks: both found a positive association. A Canadian study found that a small excess of lung cancer detected in printers as a whole was concentrated in printing process workers and was very high for adenocarcinoma of the lung in particular.
Six census-based record-linkage studies reported results for lung cancer. The Swedish study found a statistically significant 60% excess of lung cancer in blue-collar workers in printing enterprises. One study in Denmark showed an increased risk only for women employed in printing, publishing and allied industries. A subsequent Danish study revealed a slight, statistically significantly increased risk in printing and bookbinding industry workers; the risk was higher and still significant in workers employed in newspaper and magazine production. The Finnish study and the two Italian studies did not detect a statistically significant increased risk for lung cancer related to printing occupations.
Among the industry-based studies, five proportionate mortality studies evaluated the risk for lung cancer. In one study, statistically significantly increased risks were found among printing trade workers in two different areas of the United Kingdom. A subsequent, partially overlapping study in London, United Kingdom, reported a statistically significant 30% excess of lung cancer among newspaper printing workers. A third study examined United States newspaper and commercial pressmen separately; neither newspaper nor commercial pressmen showed an increased mortality from lung cancer. The other two proportionate mortality studies in printing workers in the United States failed to show an increased risk for lung cancer.
Among the industry-based studies, seven standardized mortality ratio studies examined lung cancer risk in printing trade workers. Respiratory cancer was elevated in four studies; in none was smoking controlled. An increased risk for lung cancer was found in the Italian cohort of newspaper workers. The historical cohort of trade union members in the United Kingdom printing industry had a statistically significantly increased risk for lung cancer among mainly unskilled workers in newspaper letterpress printing (machine assistants). Newspaper web pressmen in Los Angeles, United States, showed a nonsignificantly increased lung cancer risk. A Swedish study of rotogravure printers revealed increased risk from respiratory cancers.
In addition, in a cohort of United States Army veterans, an increased smoking-adjusted relative risk for respiratory cancer was found in 'printing pressmen and plate printers'.
In some studies, it was possible to separate newspaper printing workers from other less-well defined employment in the printing industries. Seven cohort studies examined lung cancer risk in workers employed in the newspaper printing industry, mainly during the period 1945-1970. Three were proportionate mortality studies, two of United Kingdom newspaper printing companies and one that examined United States newspaper pressmen and commercial pressmen separately. Four were standardized mortality ratio studies of newspaper web pressmen in Los Angeles, United States, of newspaper printers in two plants in New York City, United States, of newspaper workers in one Italian plant and of newspaper machine assistants who were trade union members in the printing industry in the United Kingdom. Five of the seven cohort studies reported increased relative risk estimates ranging from 1.2 to 1.5, of which three were statistically significant. In none of them was smoking taken into account. In addition, a Danish record-linkage study found a two-fold, statistically significantly increased risk for workers in newspaper and magazine production whose typical job was the operation of rotary letterpress machines.
Cancer of the oropharynx
The risk for cancer of the buccal cavity and pharynx was examined in three case-control studies in the United States. One study on multiple cancer sites showed a smoking-adjusted elevated risk in printing workers. Another similar study detected a significantly high smoking- and alcohol-adjusted risk for cancer of the oral cavity in workers in the printing and publishing industry. A third case-control study on oropharyngeal cancer did not find an increased risk among men employed in the printing industries, whereas a nonstatistically significantly increased risk was found for women. A nonstatistically significantly increased risk was found in male workers in printing and bookbinding industries in a Danish record-linkage study.
Four cohort studies reported results for cancer of the buccal cavity and pharynx. The United States study that examined separately newspaper pressmen and commercial pressmen found a higher than two-fold statistically significantly increased risk in newspaper pressmen only. Increased risks were not found in a standardized mortality ratio study of newspaper pressmen in Los Angeles nor in a cohort of newspaper printers in two plants in New York City. The cohort of trade union members in the United Kingdom printing industry found increased risks in non-production workers (editorial and clerical staff) only.
Urinary bladder cancer
Thirty-five studies have reported findings for urinary bladder cancer and employment in the printing industry. A positive association between urinary bladder cancer and either a printing occupation or employment in the printing industry was reported in 14 of the 23 case-control studies. The range of relative risk estimates derived from these studies was from 1.1 to 5.6. These associations were statistically significant in only three of the case-control studies. Generally, the interpretation of the case-control studies was limited by their use of broad job and industry categories such as printers or the printing industry. One study in Spain reported a nonsignificantly increased relative risk for typesetters and linotypists.
Six cohort studies and six record-linkage studies have also been reported. Increased rate ratios were reported in five of the cohort studies of workers in the printing industry. However, the rate ratios in two of them were close to 1.0 and a statistically significant increase was found only for printing pressmen and plate printers in the cohort of United States Army veterans. Similarly, the relative risk estimates derived from the record-linkage studies were close to unity and the only ones that achieved statistical significance were from the two Danish studies: one study found an increased risk among men employed in printing and bookbinding industries and the other among men employed in printing, publishing and allied industries. Five case-control studies reported results for exposure to printing inks and urinary bladder cancer risk was observed to be elevated in all five studies.
Cancer of the kidney
Slight to moderate excesses of cancer of the kidney have been reported in the printing industry in five industry-based studies in different cohorts in the United States, and in two record-linkage studies in Italy and Sweden. Ten cohort studies did not report results for cancer of the kidney at all. Four case-control studies, one nested in a cohort of paperboard printing workers and three representing different populations in three continents reported odds ratios ranging from 1.3 to 16.6. Most of these were not statistically significant. By far the most powerful case-control study, a multicentric study conducted in Australia, Denmark, Germany, Sweden and the United States, reported a 30% nonsignificant excess associated with employment in printing and graphic industry.
Leukaemia
Results regarding leukaemia risk in printing workers have been reported in one case-control study and seven cohort studies. The case-control study found a nonstatistically significantly increased risk for printers. Significantly increased risks were found in two cohort studies.
The proportionate mortality study that examined newspaper pressmen and commercial pressmen separately found a 60% excess of leukaemia risk only in newspaper pressmen. In another proportionate mortality study in printing workers in the United States, a statistically significantly increased risk for leukaemia was detected primarily among bindery workers who may have had exposure to benzene. Newspaper web pressmen in Los Angeles, United States, also showed a higher than two-fold increased risk. A Swedish study of rotogravure printers revealed an increased risk for leukaemia, although this was based on a very small number of cases. Both newspaper web pressmen and rotogravure printers may have been exposed to benzene and other organic solvents in the past. Three other cohort studies in newspaper printing workers in London, United Kingdom, commercial pressmen in the United States and newspaper printers in New York City failed to show an increased risk.
Overall, notwithstanding the variability in the results, there are indications of excess risks among printing process workers for some types of cancer. In its evaluation of these data, the Working Group considered the likelihood of publication bias, the possibility of confounding by cigarette smoking, and the imprecision and inconsistency of the designation of exposure groups. Based on these considerations, the Working Group concluded that there is weak evidence of an increased risk of lung and urinary bladder cancers among workers in the printing industry.
While there was a suggestion of an increased risk of lung and urinary bladder cancers in relation to exposure to printing inks, the quality of the data was weak.
The Working Group noted that the vast majority of epidemiological studies covered workers who were in the printing industry in North America or Europe during the middle of the twentieth century. Very few of the studies included workers whose employment was after 1980. Given the rapid technological changes that have gone on in this industry in North America and Europe in the past decade, it is questionable whether the exposure circumstances that were prevalent in the past are still prevalent. However, there may be areas of the world in which the older processes are still prevalent. Where the technologies have substantially changed from those of the past and insofar as this has changed the exposure conditions, the present evaluation may not be relevant.
5.3 Animal carcinogenicity data
Twenty-two different printing inks were tested for carcinogenicity in one study in mice by subcutaneous injection. The study was inadequate for evaluation.
5.4 Other relevant data
No consistent association between employment in printing trades and morbidity from non-malignant diseases has been observed. Solvent-induced central nervous system damage has been observed in several but not all studies on employees in printing trades. Ultraviolet radiation-cured printing inks are a frequent cause of allergic contact dermatitis.
One study suggested that occupational exposures may induce hepatic damage in printers, but several other studies failed to confirm this finding.
An early report of an increased risk of anencephalus associated with paternal employment in printing has not been confirmed in subsequent studies of neural tube defects. In two studies, an association between this exposure and cleft lip and/or palate has been observed. However, in one of these, the association was apparent only for cleft palate, and in the other only for cleft lip, and no noteworthy association has been observed in a further three studies. In a single study in rats, dermal exposure to newspaper inks had no effect on sperm numbers or motility, vaginal cytology or oestrus cycle length.
Several pigments and dyes used in printing inks are mutagenic in Salmonella typhimurium: para red, dinitroaniline orange, azo dye D & C Red No. 9.
An increased frequency of chromosomal aberrations in peripheral lymphocytes in printing workers exposed to inter alia toluene was found in two studies, but not in two other studies. In one study, an increased frequency of chromosomal aberrations was found in workers exposed to toluene and benzene. In one study of a group exposed to toluene, an increased frequency of sister chromatid exchange was found, but not in two other studies. In one study of printers exposed to lead, increased frequencies of chromosomal aberrations and sister chromatid exchange were found. In one study, an increased frequency of micronuclei was observed in printing workers exposed to toluene. In one study of volunteers exposed to toluene, no increase in sister chromatid exchange was observed in lymphocytes.
5.5 Evaluation
There is limited evidence that occupational exposures in printing processes are carcinogenic.
There is inadequate evidence for the carcinogenicity in humans of printing inks.
There is inadequate evidence for the carcinogenicity in experimental animals of printing inks.
Overall evaluation
Occupational exposures in printing processes are possibly carcinogenic to humans (Group 2B).
Printing inks are not classifiable as to their carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
See Also:
Toxicological Abbreviations