Carbon black
In a report based on an evaluation performed in February 2006, International Agency for Research on Cancer classified carbon black as Group 2B - possibly carcinogenic to humans (IARC, 2010). Subsequently, analysis of data from 1147 workers in five factories in the United Kingdom suggested that carbon black might have a late stage effect in respiratory carcinogenesis. Nevertheless, there was heterogeneity across the five plants with a significant association at only two of the five plants. This finding was not replicated in a set of comparable analyses in a German cohort of 1528 carbon black workers; and in this same cohort, there was no indication of increased lung cancer risk. Lung cancer risk was also not elevated in cohorts of German rubber workers and of US black carbon workers. In two case-control studies in Montreal, carbon black was not associated with increased lung cancer risk. In the Xerox workers, who had exposure to carbon black in toner particles, the researchers also did not find an increased risk of lung cancer. It is also important to note that carbon black in commercially available toners is non-respirable and is bound within the toner particle. In conclusion, this analysis evaluated 3374 deaths occurring over 832,064 person-years of follow-up time (average follow-up time 26 years). The results of this analysis are consistent with the general mortality patterns among healthy working populations. No evidence was found that toner exposure increases the risk of all cause or cause-specific mortality for 23 categories of cause of death (Abraham et al, 2010).
Interestingly, the US ACGIH derived a TLV (3 mg/m3, inhalable particulate matter, TWA) for carbon black based on bronchitis as primary effect. The most important health outcomes from elevated exposure to carbon black appear to be respiratory symptoms; decreased lung function; possible changed in the lung as indicated by changes on chest X-ray; and in the rat carcinogenesis (ACGIH, 2011). The carcinogenic effects, which were seen in rat studies under overload conditions, are considered to have questionable predictive power for human lung cancer (Mauderly, 1997).
Carbon blacks are characterised by the size distribution of the primary particles and the degree of their aggregation and agglomeration. Human exposure is primarily to carbon black particles in aggregate and agglomerate forms. Average aggregate particle diameters in several commercially produced carbon blacks range from 50 to 600 nm and the more loosely associated agglomerates can reach up to many micrometres in diameter. The majority of carbon blacks currently manufactured have small quantities (< 1%) of organic compounds, including polycyclic aromatic hydrocarbons, adsorbed onto their surface (IARC, 2010).
About 90% of carbon black is used in rubber products, predominantly in tires. Carbon black is also used as a pigment in inks, paints and coatings and in plastics (IARC, 2010).
Exposures to carbon black vary markedly between and within production facilities and over time. The highest levels of exposure are experienced by packers and site cleaners. Some studies prior to 1970 found that extremely high levels of carbon black exposure could have occurred in the carbon black manufacturing industry. Exposure studies in this industry in the USA and western Europe after the late 1970s found personal inhalable dust exposures to be less than 5 mg/m3 (geometric mean). By the mid to late 1990s the inhalable dust levels were below 2 mg/m3 (geometric mean); the respirable dust levels were below 0.5 mg/m3. No data were available that would allow the characterisation or quantification of exposure to ultrafine primary particles (IARC, 2010).
The study of workers in five carbon black production facilities in the United Kingdom involved a large group with a long follow-up. When compared with national mortality rates, there was a clear excess of mortality from lung cancer. Although smoking histories were not known, there was no corresponding excess of other diseases known to be associated with smoking. The excess risk was manifest in two of the five factories. Exposure was assessed using last job from worker records and a job–exposure matrix based on expert judgment and measurements from two of the five plants. When adjusted for age and divided into four subgroups based on cumulative exposure levels, relative risk for lung cancer did not increase monotonically with increasing exposure, although the two highest exposure categories showed higher relative risks than the two lowest categories. There was no excess risk for cancer at any other site (IARC, 2010).
A cohort study was conducted among blue-collar workers in a long-standing, large German carbon black production plant. When mortality was compared with regional rates, there was an approximate doubling of risk for lung cancer. Exposure was assessed using full work history records from the plant and expert judgments. Further, company medical records provided some information on tobacco smoking for most of the workers. Compared with the lowest exposure group, after adjusting for smoking, and using several indices of exposure, there was no indication that workers with higher exposure to carbon black had higher risks. However, the precision of these subgroup risk estimates was low. There were no excess risks for most other cancer sites, including oesophagus, stomach and urinary bladder, although the numbers were small (IARC, 2010).
Another group of investigators analysed the same German cohort of carbon black workers, but used rather different methods. They confirmed that there was no exposure–response relationship within the cohort between estimated exposure to carbon black and lung cancer. After accounting for regional variations in cancer and different methods of adjustment for tobacco smoking and other exposures, the overall risk for lung cancer was slightly elevated, although the Working Group was not persuaded that all the adjustments were warranted (IARC, 2010).
The US study included a large cohort of workers from 18 plants with good ascertainment of cohort members and effective mortality follow-up over a long period of time. There was no indication of excess risk for cancer at any of the reported cancer sites. There was no indication that long-service workers had higher risks than short-service workers. For most types of cancer, including lung cancer, the numbers of deaths observed did not exceed the numbers expected on the basis of national rates. No results were provided according to levels of exposure to carbon black, and the analyses did not take into account tobacco smoking habits (IARC, 2010).
Summary evaluation
Overall, seven studies were considered to be informative for lung cancer, of which three were among carbon black production workers. The IARC Working Group considered the studies of carbon black production workers in the United Kingdom, Germany and the USA to be the most informative for assessing cancer risk. The two studies from the United Kingdom and Germany indicated excess risk compared with external references. Confounding by smoking could not be excluded, although it was unlikely to have explained the entire excess risk. However, in both cohorts, internal analyses by level of exposure to carbon black gave equivocal but mainly null results. The study of carbon black workers in the USA suggested no excess mortality, but did not assess risk by level of exposure. In studies that assessed risks for lung cancer among user industries, the most informative study of German rubber workers showed some indication of excess risk that disappeared when asbestos and talc were adjusted for in the analysis. Of the remaining studies, two others showed non-significant excesses (US formaldehyde cohort and the Canadian community-based case–control study) and one showed no excess risk for lung cancer linked to the handling of carbon black (Italian dockworkers). For cancers of the urinary bladder, kidney, stomach and oesophagus, isolated results indicate excess risks, but these are not sufficient to support an evaluation of human carcinogenicity. There is no evidence of an effect of carbon black for other cancer sites (IARC, 2010).
The deposition pattern of carbon black particles depends on the particle size (aerodynamic or thermodynamic) and on the anatomical and physiological characteristics of the host. The deposition fraction of carbon black influences the dose to a given region of the respiratory tract. Several studies describe the retention of carbon black in the respiratory tract of exposed workers, as well as the health effects of these exposures. For example, lung tissues from workers in carbon black factories contain deposits of carbon black. Lung diseases or conditions may influence the deposition and retention of particles such as carbon black. For instance, asthmatics had a higher total deposition of ultrafine carbon particles in the respiratory tract compared with healthy individuals. The amount of carbon particles deposited can also increase with increasing minute ventilation, for instance in individuals taking exercise or during heavy physical labour. High retained mass lung burdens and decreased lung clearance have been observed in coal miners (IARC, 2010).
Non-cancer respiratory effects in carbon black workers that have been reported include cough, sputum production, bronchitis, chest radiographic opacities (e.g. pneumoconiosis) and decrements in lung function (IARC, 2010).
There are many studies on the deposition and retention kinetics of inhaled carbon particles following intratracheal instillation or inhalation in rodents. In general, all rodent species investigated show evidence of rapid clearance of inhaled carbon particles when exposure concentrations did not result in impaired clearance resulting in accumulation of particles in the lung (i.e. lung overload). The experimental studies of ultrafine particles of carbon black have shown that rodents experience dose-dependent impairment of alveolar macrophage-mediated clearance, which occurs at lower mass doses of ultrafine particles than with larger particles. Overloading has been observed in rats, mice and hamsters exposed to carbon black. Hamsters appear to exhibit the most efficient clearance of carbon black particles compared with rats and mice. Adverse lung responses to inhaled carbon black (pulmonary inflammation and epithelial injury) increase significantly with increasing retained lung dose of carbon black particles. Fine and ultrafine carbon black particles can translocate beyond the lungs to other organs (IARC, 2010).
A number of toxic effects of carbon black have been reported in various rodent species. The toxic effects reported are dose-dependent and include inflammation, lung epithelial cell injury and lung lesions that are more severe and prolonged in rats than in mice and hamsters. Exposure to carbon black particles modulates the immune system. In vitro studies show evidence that carbon black particles can generate reactive oxygen species in cell-free systems, increase the production of tumour necrosis factor-α and activate serum factors such as complement (IARC, 2010).