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IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. Arsenic, Metals, Fibres and Dusts. Lyon (FR): International Agency for Research on Cancer; 2012. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 100C.)

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Arsenic, Metals, Fibres and Dusts.

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Leather dust was considered by previous IARC Working Groups in 1980 and 1987 (IARC, 1981, 1987). Since that time, new data have become available, these have been incorporated in the Monograph, and taken into consideration in the present evaluation.

1. Exposure Data

1.1. Identification of the agent

Leather is the product obtained by tanning skins and hides by any one of several methods. By convention, the term ‘hide’ generally refers to the skin-covering of larger animals (cows, steers, horses, buffaloes, etc.), and the term ‘skins’, to those of smaller animals (calves, sheep, goats, pigs, etc.). Although the physical properties of these different skins vary, their basic chemical, physical, and histological characteristics are similar (IARC, 1981).

1.2. Chemical and physical properties of the agent

The skin is mainly composed of proteins, although it also contains lipids, carbohydrates, inorganic salts, and water. From the point of view of leather manufacture, the proteins of the skin are the most important components. These proteins include collagen (constitutes the bulk of the fibrous portion), and reticulin (similar to collagen, but differing in its ability to combine readily with silver salts). Elastin, also a fibrous protein, is present in very small quantities, mainly in the grain area, and to a small extent in the blood vessels. Most of the non-collagenous proteins are removed during pre-tanning operations, which are effectively a means of preparing a matrix of relatively pure collagen fibres that will subsequently be stabilized by tanning (IARC, 1981).

Tanning is any process that renders animal hides or skins imputrescible without impairing their flexibility after drying. The most commonly used tanning agents have been vegetable tannins, and basic chromium (III) sulfate.

The vegetable tannins fall into two broad chemicals groups: hydrolysable tannins and condensed tannins. Condensed tannins are more complex chemical structures, and are more likely to be found in the bark or wood of a tree, whereas the hydrolysable tannins predominate in the leaves and fruits. Hydrolysable tannins are mainly glucosides (i.e. glucose esterified with polyhydroxyl phenyl carboxylic acids, such as gallic and ellagic acids) that readily ferment to release the free acid used in primitive tanning processes to control acidity. The chemistry of condensed tannins is complex, and they have been identified as oligomers containing 4–10 flavonoid units, each containing 4–6 hydroxyl groups. Molecular weights in non-aqueous solvents range from 1000–3000, although measurements in aqueous solution suggest aggregation or association to give an effective molecular weight of approximately 10000 (IARC, 1981).

In chrome tanning, the trivalent chromium ions form polynuclear complexes involving, typically, four chromium atoms. Ring structures containing coordinated sulfate and hydroxyl ligands are formed, giving an effective ionic weight of approximately 800. When skins are immersed in a solution of basic chromium (III) sulfate, carboxyl side chains on the collagen enter the coordination sphere of the chromium to form an insoluble complex. This reaction, which invariably involves cross-linking, is the basis of chrome tanning (IARC, 1981).

The composition of leather used in the leather-product industries varies. For example, leather used in shoe manufacture may come from the corium part of hide skin processed during tanning. The composition of crust leather varies depending on the tanning processes (Buljan et al., 2000). The reported chromium (III) levels in dust from chrome-tanned leathers have varied from 0.1% to 4.5% by weight (IARC, 1981). Leather may also contain trace amounts of chromium (VI) formed by oxidation of trivalent chromium during the tanning process. For example, in a Danish study of 43 leather products, 35% (n = 15) contained chromium (VI) at levels above the detection limit of 3 mg/kg (Hansen et al., 2002).

1.3. Use of the agent

The hides or skins from different animals possess unique physical properties that are inherent to the particular animal or breed of animal, due largely to differences in climate, type of feed, etc., to which the animal is exposed. They are thus used for different specific purposes (Table 1.1). For more detailed descriptions, refer to the previous IARC Monograph (IARC, 1981).

Table 1.1. Leather uses in relation to type of hide or skin.

Table 1.1

Leather uses in relation to type of hide or skin.

1.4. Occupational exposure

For detailed descriptions of historical exposures to leather dust and other agents in the workplace, refer to the previous IARC Monograph (IARC, 1981).

1.4.1 Extent of occupational exposure

Leather and leather-product industries have moved gradually from the industrialized countries to the developing world. For example, shoe manufacture in the United States of America decreased by more than 90% during 1965–2002, and the largest footwear exporter to the USA was the People’s Republic of China (Markkanen & Levenstein, 2004). China produced 40% of all prepared shoes in the world at the end of the last century (Chen & Chan, 1999), and the number of employees in shoe manufacture in China was estimated to be about 2 million (Wang et al., 2006). It was reported that Asian countries supply over 80% of the footwear traded in the world market, and the largest production comes from China followed by India, Indonesia, Viet Nam, Thailand, and Pakistan (Vachayil, 2007). In several developing countries, large and medium-sized manufacturers and retailers are known to use subcontracting practices, informal employment, and so-called home-based shoemaking. There are no reliable estimates on the informal workforce, but it is assumed to be even higher than in the formal sector (Markkanen & Levenstein, 2004). According to statistics from the International Labor Organization, other major countries producing leather products were Mexico (n = 302000 employees), Brazil (n = 305000), Indonesia (n = 279000), the Russian Federation (n = 190000), and Italy (n = 168000) (ILO, 2004).

Although several million people are working in the leather and leather-product industries, only a fraction are exposed to leather dust and other air contaminants in the workplace. No worldwide estimates of the numbers of workers exposed were available to the Working Group.

1.4.2 Levels of occupational exposure

Leather dust concentrations in selected studies published since the previous IARC Monograph (IARC, 1981) are presented below.

(a) Footwear industry

In a Russian mortality study of 5185 shoe-manufacturing workers employed during 1940–76, Zaridze et al. (2001) reported leather dust concentrations in the range of 6.5–12 mg/m3 in the following production departments: cutting, fitting, lasting and making, and finishing. In this factory, leather dust was present as a co-exposure with solvents and chloroprene.

Shoe repairers are exposed to the dusts generated during scouring. In a Finnish study of shoe repairers from 11 shops, the time-weighted average concentrations of dust were in the range of 0.07–1.0 mg/m3 in the vicinity of the roughing, scoring, and finishing machines. The dust concentration depended on the age and type of the machine, and the performance of its local exhaust. Electron-microscopic studies showed that the dust samples collected during the machining of shoes contained leather, polymers, and finishing materials. Several degradation products of polymers were present. Dust was formed mainly during the machining of shoes. Dust samples contained also low concentrations of insoluble chromium (0.10–0.32 μg/m3), and hexavalent chromium (0.01–0.08 μg/m3) (Uuklainen et al., 2002).

In a Polish study, dust concentrations were higher in shoe-repair shops than in shoe manufacture. In the repair shops, the recorded concentration of inhaled dust fraction was in the range of 0.5 mg/m3 (glueing of shoes and soles, zipper exchange, and heel abrasion) to 0.9 mg/m3 (sewing of uppers and scouring of heels), with high short-term (> 1 minute) fluctuations in the range of 0.1–14.6 mg/m3. In the shoe factories, the mean concentration of inhalable particles (sample duration > 8 hours) was in the range of 0.12–0.91 mg/m3, but there were high short-term (> 1 minute) fluctuations in the range of 0.62–6.4 mg/m3 (Stroszejn-Mrowca & Szadkowska-Stańczyk, 2003).

(b) Leather-tanning and -processing industry

Dust is produced during several processes in tanning operations: chemical dust can be produced during the loading of hide-tanning drums; and leather dust impregnated with chemicals is produced during some mechanical operations, including buffing (IARC, 1981). Total dust levels (personal and static) measured in three countries were presented in Table 2 of the previous IARC Monograph (IARC, 1981). Personal levels ranged from a low of 0.1 mg/m3 in buffing to a high of 21 mg/m3 in semi-automatic staking (IARC, 1981).

1.4.3 Particle size distribution

Leather dusts can contain both fibres and grains; the fibres can vary from 30–1200 μm in length and from 10–30 μm in diameter. Grains are usually < 10 μm in diameter. In several surveys in Italy, more than 50% of the total dust in tanneries were reported with having a particle diameter of < 5 μm (IARC, 1981).

Particle sizes have been measured in the dust generated at various workstations in the shoe trade in Poland. The median particle diameter was about 10 µm, and the proportion of extrathoracic particles which would lodge in the nasal fossae was 35–52%, depending on the occupation (Stroszejn-Mrowca & Szadkowska-Stańczyk, 2003).

1.4.4. Exposure to other agents

(a) Footwear industry

Appendices 5 and 6 of the previous IARC Monograph list the various chemicals which may occur in the footwear industry. Most are different solvents used in adhesives, lacquers or cleaning agents. They include petroleum hydrocarbons, chlorinated hydrocarbons, ketones, esters, and alcohols (IARC, 1981). Benzene was previously widely used as a solvent in the shoe industry, and exposure levels during that period may have been high. For example, in Italy, the estimated concentrations of benzene in one shoe factory during 1939–65 were in the range of 0–92 ppm (300 mg/m3). The highest exposures occurred in 1954–60, and benzene was banned by legislation in Italy in 1965 (Seniori Costantini et al., 2003).

Wang et al. (2006) reviewed 182 articles on benzene exposure in the shoemaking industry in China during 1978–2004. In 1979–2001, 65% of the measurements exceeded the national occupational exposure limit (OEL) of 40 mg/m3 (13 ppm), and 20% of these exceeded 500 mg/m3 (154 ppm). Benzene levels above 1000 mg/m3 (308 ppm) were not uncommon, and some were in excess of 4500 mg/m3 (1385 ppm). It was also reported that, in some cases, pure benzene was used during the 1980s. The national OEL was lowered to 6 mg/m3 (2 ppm) in 2002, but only 24% of the reported measurements in 2002–04 were below the OEL. The average benzene levels in 2002–04 were 25.1 mg/m3 (8 ppm) in fitting uppers with soles, and 73.6 mg/m3 (23 ppm) in the making of soles. The tasks where exposure occurred most often were fitting uppers with soles, soles-making, uppers-embedding, and uppers-making. Benzene-based adhesives are now banned in China and the national standard for benzene in adhesives is regulated to be less than 0.5% (Wang et al., 2006).

At a large shoe factory in Tianjin, China, as part of a cross-sectional study, Vermeulen et al. (2006) collected dermal, inhalation, and urine samples (n = 113) from 70 subjects performing representative tasks and operations at the plant. Mean airborne concentrations of benzene and toluene were 1.52 (standard deviation (SD) 2.82) and 7.49 (SD 11.60) ppm, respectively.

Historically, many toluene-based adhesives manufactured in China contained about 10–30% of benzene as impurity (Chen & Chan, 1999). Exposure to other solvents varies widely, but the levels in some factories may be high. For example, in Viet Nam the national OEL of toluene 100 mg/m3 (26 ppm) was exceeded by six times or more in different sections of a shoe-manufacturing plant in 1996. The concentration of acetone was 6–18 times the Vietnamese OEL 200 mg/m3 (84 ppm) (Chen & Chan, 1999).

Leather dust may also contain agents originating from the processing of leather in tanneries. Levels of chromium (VI) compounds in leather dust are usually very low (see Section 1.4.2a). Leather dust may also contain dyes. Dyes which have been used in the boot and shoe industry include seven dyes classified by IARC in Group 2B (possibly carcinogenic to humans): CI Acid Red 114 (CAS, 6459-94-5), auramine (CAS, 492-80-8), benzyl violet 4B (CAS, 1694-09-3), Trypan blue (CAS, 72-57-1), Ponceau MX (CAS, 3761-53-3), Ponceau 3R (CAS, 3564-09-8), and Rosaline (CAS, 632-99-5) in Magenta (IARC, 1981).

Other agents that may or may not have occurred in the footwear industry include salts of chlorophenols (preservative of leather), acrylic resins, isocyanates (reactive primers, two-part adhesives), polyurethanes and other polymers (artificial leather), chloroprene (component of polychloroprene latex), and wood dust (making of wooden shoes and models) (IARC, 1981).

(b) Leather-tanning and -processing industry

Appendices 5 and 6 of Volume 25 list chemicals that may occur in leather tanning (IARC, 1981).

Exposure to chromium (III) salts or vegetable tannins may occur during the weighing and introduction of chromium salts into rotating drums. Also, small amounts of chromium (VI) may be present. Sodium chlorophenates may be used to prevent the deterioration of leather during tanning, and to protect it from mould. Other possible exposures in the tanyard are sulfuric acid and hydrogen sulfide. If dimethylamine is used in the tanning process, N-nitrosodimethylamine may be produced (IARC, 1981).

The use of benzidine-based dyes has been reported in the retanning, colouring, and fat-liquoring departments of the leather-tanning and –processing industry. A wide array of chemical solvents (e.g. tetrachloroethylene, toluene, xylene, methyl ethyl ketone and isopropanol), pigments, and waxes may be used in the finishing departments. Exposure to formaldehyde may also occur (IARC, 1981).

(c) Other leather-product industries

Exposures in industries producing leather bags, wallets, suitcases, leather-wearing apparel, harnesses, leather furniture and other miscellaneous leather goods are similar to those that occur in the footwear industry (see Section 1.4.2a).

2. Cancer in Humans

The boot and shoe industry was first reviewed in the previous IARC Monograph IARC (1981). The then Working Group reviewed the results of case series on cancer of the nasal cavity and paranasal sinuses (referred below as sinonasal cancer), several of which compared the history of exposure among adenocarcinoma cases to other cancer controls. The then Monograph Working Group also reviewed the results of case series and case reports of leukaemia, as well as other studies focused on bladder, lymphatic and haematopoietic, oral/pharyngeal, lung, and stomach cancer. The Working Group concluded that “Employment in the boot and shoe industry is causally associated with the development of nasal adenocarcinomas” and that “It is most likely that exposure to leather dust plays a role in the association.” The Working Group also concluded that an increased risk for other histological types of nasal cancer “may exist.” They also observed that “The occurrence of leukaemia and aplastic anaemia among shoe workers exposed to benzene is well documented.” They noted that excesses of bladder cancer were associated with the leather industry, but it was not clear if these could be attributed to shoe workers. They also reported that hypothesis-generating studies had observed excesses associated with cancer of the lung, oral cavity, pharynx, and stomach.

The boot and shoe industry was re-reviewed as part of the previous IARC Monograph Supplement 7 (IARC, 1987). In the period following the publication of Volume 25 several new studies had been published. The Working Group for supplement 7 had access to a new retrospective cohort study, three new proportionate mortality studies, as well as new case–control studies of sinonasal cancer and other cancer sites. The conclusions of the Working Group for Supplement 7 were concordant with those of Volume 25. They also concluded that nasal adenocarcinoma was associated with the boot and shoe industry, and that the highest risk was among those with high exposures to leather dust. They also noted that there was evidence for other types of nasal cancer, and that there was further evidence of an increased risk of leukaemia associated with exposure to benzene in the industry. Mixed evidence that may indicate an excess risk of bladder cancer among shoe workers was also noted. Some associations with lung, oral, pharynx, and stomach cancer as well as kidney cancer and mesothelioma were also observed.

In this Monograph, studies published in the time following Supplement 7, as well as others that were not previously considered, are reviewed. Of special note are the retrospective cohort studies. The previously reviewed retrospective cohort study of workers in the boot and shoe industry in three English towns (Pippard & Acheson, 1985) has been updated and the end of follow-up extended to 1991, and the cohort study of Florence shoe workers exposed to benzene (Paci et al., 1989) has also been updated and the follow-up extended to 1991 for a pooled analysis (Fu et al., 1996). A US study of shoe workers focused on exposure to solvents, mostly toluene (Walker et al., 1993), has also been updated (Lehman & Hein, 2006). A Russian study of shoe manufacturing workers focused on exposure to chloroprene has also been published (Bulbulyan et al., 1998). The results of registry-based studies are presented in Table 2.1. Descriptive studies with information based only on death certificates are not included. The methods and results of relevant cohort and related studies are summarized in Table 2.2. Only the most recent results are presented in cases where the cohorts were updated. Also included in Table 2.2 are the methods and results of the previously reported proportionate mortality studies.

Table 2.1. Descriptive and census-based studies.

Table 2.1

Descriptive and census-based studies.

Table 2.2. Cohort studies of boot and shoe workers.

Table 2.2

Cohort studies of boot and shoe workers.

The results of relevant case–control studies of sinonasal cancer, including those previously reviewed, are summarized in Table 2.3. Studies of other respiratory cancers are summarized in Table 2.4. Case–control studies of bladder cancer are summarized in Table 2.5. Case–control studies of other cancer sites are summarized in Table 2.6. For case–control studies, only those that assessed the association with boot/shoe workers, the broader category of leather products, or with leather dust are included. Those that explicitly included tannery workers, which have a very different set of exposures, were excluded.

Table 2.3. Case–control studies on sinonasal cancer in shoe workers or workers exposed to leather dust.

Table 2.3

Case–control studies on sinonasal cancer in shoe workers or workers exposed to leather dust.

Table 2.4. Case–control studies on respiratory cancer in shoe workers or workers exposed to leather dust.

Table 2.4

Case–control studies on respiratory cancer in shoe workers or workers exposed to leather dust.

Table 2.5. Case–control studies on cancer of the bladder in shoe workers or workers exposed to leather dust.

Table 2.5

Case–control studies on cancer of the bladder in shoe workers or workers exposed to leather dust.

Table 2.6. Other case–control studies with results for shoe workers or workers exposed to leather dust.

Table 2.6

Other case–control studies with results for shoe workers or workers exposed to leather dust.

2.1. Sinonasal cancer

An unusual high prevalence of sinonasal cancer among boot and shoe or other leather workers observed in case series from the Northamptonshire region of England first cast suspicion on a possible association between the malignancy and the occupation (Acheson et al., 1970a, b; Acheson, 1976). In the period following the previous IARC Monograph Supplement 7, case series continued to report cases of sinonasal cancer among workers that had been employed as shoe workers or exposed to leather dust. For example, Barbieri et al. (2005) reported that seven of 100 epithelial sinonasal cancer cases in the Province of Brescia, Italy, were exposed to leather dust with an average latency of 44 years. A large French adenocarcinoma case series reported that 11 of 418 cases had been exposed to leather dust, whereas 353 had been exposed to wood dust (Choussy et al., 2008). [The Working Group noted that even though leather workers are the second most frequently reported group in these sinonasal cancer case series, it is difficult to interpret these results without knowing the prevalence of leather work in the source population.]

Results of descriptive studies from the United Kingdom and the Nordic countries are presented in Table 2.1. High relative risks were observed, particularly when presenting results for adenocarcinoma (Acheson et al., 1970a, 1982). Relative risks in more recent studies are somewhat lower, but still significantly elevated (Acheson et al., 1982; Olsen, 1988; Andersen et al., 1999).

A large excess was reported in the pooled English and Florence cohorts, based on 12 and one cases observed, respectively (Fu et al., 1996). The risk of sinonasal cancer was associated with probable exposure to leather dust in the English cohort (Fu et al., 1996), and the excess was reported to be greatest in the finishing area in the earlier report on the English cohort (Pippard & Acheson, 1985). Results for sinonasal cancer were not reported for the Russian and American shoe-manufacturing cohorts (Bulbulyan et al., 1998; Lehman & Hein, 2006). The US cohort study reported there was ‘no evidence of any significant level of exposure to leather dust.’ No sinonasal cancer cases were reported in any of the three proportionate mortality ratio (PMR) studies. There were 2.2 and 1.9 expected cases in the studies of Decouflé & Walrath (1983) and Walrath et al. (1987), respectively. Expected numbers were not reported for Garabrant & Wegman (1984), see Table 2.2.

Fourteen sinonasal case–control studies and one pooled re-analysis of seven European studies were reviewed. Twelve of the 14 studies observed evidence of an excess of sinonasal cancer, although sometimes based on very small numbers. The largest odds ratios were observed in the Italian studies, with odds ratios in the range of 3.5 (95%CI: 0.6–2.3) (Magnani et al., 1993) to 121 (95%CI: 17.3–844) for heavy leather dust exposure (Merler et al., 1986). In addition, two studies reported an infinite risk (Cecchi et al., 1980 with seven cases and zero controls; Bimbi et al., 1988 with three cases and zero controls). Excesses were also observed in studies from Sweden (Hardell et al., 1982), Japan (Shimizu et al., 1989), Germany (Bolm-Audorff et al., 1989, 1990), and France (Luce et al., 1992, 1993). The only non-positive studies were from the USA (Brinton et al., 1984) and Canada (Teschke et al., 1997), the only North American studies. The pooled re-analysis of European case–control studies observed increased risks associated with leather dust exposure among both men (OR, 1.9; 95%CI: 1.1–3.4) and women (odds ratio [OR], 2.7; 95%CI: 0.8–9.4), see Table 2.3.

Relative risks (RR) for adenocarcinoma were consistently high in descriptive (Acheson et al., 1970b, 1982) and case–control studies (Cecchi et al., 1980; Merler et al., 1986; Comba et al., 1992a; ’t Mannetje et al., 1999a). However, smaller excess risks were also observed in the few cases where squamous cell carcinoma results were presented (Shimizu et al., 1989; Luce et al., 1992, 1993; ’t Mannetje et al., 1999a).

In reviewing trends from Northamptonshire, the United Kingdom, Acheson et al. (1982) noted that the majority of cases had been employed in the departments with the most dusty operations, and that they had much higher risk compared to other operatives (RR, 4.5; 95%CI: 2.8–6.8). The retrospective cohort study of workers employed in the British boot and shoe industry also observed the highest risks among workers employed in the jobs with the highest exposure to leather dust (Pippard & Acheson, 1985). This was also observed in the update of the British cohort for the pooled analysis (Fu et al., 1996). An increased risk among workers with the highest leather dust exposure was also observed in case–control studies that reported results for leather dust exposure (Merler et al., 1986; Luce et al., 2002). Most other case–control studies did not provide details regarding leather dust exposure, although Loi et al. (1989) did report that four of five leather workers were milling-machine operators, a group thought to have high leather dust exposure. In a pooled analysis of European studies ’t Mannetje et al. (1999a) observed an excess of adenocarcinoma (OR, 3.0; 95%CI: 1.3–6.7) as well as a possible increase for squamous cell carcinoma (OR, 1.5; 95%CI: 0.7–3.0).

2.2. Other respiratory cancers

None of the cohort or PMR studies reported results for the pharynx alone (Table 2.2). Among the three US PMR studies, Decouflé & Walrath (1983) and Walrath et al. (1987) observed slightly more cases than expected, but Garabrant & Wegman (1984) observed slightly less cases than expected. Tarvainen et al. (2008) observed an excess of oral and pharyngeal cancer among shoe makers in Finland based on only two cases. Gustavsson et al. (1998) observed an excess risk of squamous cell cancer associated with leather dust for both oral (OR, 2.2; 95%CI: 0.5–8.7) and pharyngeal (OR, 2.8; 95%CI: 0.8–10.2) cancer. Laforest et al. (2000) found no association between exposure to leather dust and squamous cell carcinoma of the hypopharynx. Boffetta et al. (2003) did not report separate results for the pharynx, but observed an excess of carcinomas of the larynx and hypopharynx among shoe finishers, but not shoe makers or repairers, see Table 2.4.

No excesses of cancer of the larynx were observed in the updated English or Italian cohorts or the three PMR studies (Table 2.2). Results for cancer of the larynx were not reported in the Russian or US cohorts. Gustavsson et al. (1998) observed an excess risk of squamous cell carcinoma of the larynx associated with leather dust exposure (OR, 2.1; 95%CI: 0.7–6.6). Laforest et al. (2000) found no association (OR, 0.9; 95%CI: 0.6–1.3) between exposure to leather dust and squamous cell carcinoma of the larynx. Boffetta et al. (2003) observed an excess of carcinoma of the larynx among shoe finishers (OR, 4.4; 95%CI: 1.0–18.8) that was not associated with duration of employment.

No excesses of lung cancer were observed in the updated English or Italian cohorts (Fu et al., 1996). An excess was observed among men, but not among women in the Russian cohort (Bulbulyan et al., 1998). The excess was limited to workers exposed to non-solvents who were also identified as having potential exposure to leather dust. An excess of lung cancer among both men and women was observed in the US cohort, which was not related to duration of employment (Lehman & Hein, 2006). Using indirect methods, the authors estimated that part, but not all, of the excess could be due to increased smoking rates among blue-collar workers. Although a small, but significant excess of lung cancer was observed among men (PMR, 1.2; P < 0.05) in Decouflé & Walrath (1983), no such excess was observed among women in the same study or among either sex in the other two PMR studies. In a pooled analysis of two German case–control studies, an excess risk for lung cancer among both male and female shoe workers was observed (Jöckel et al., 2000). An excess was also observed in a a small Argentine case–control study (Matos et al., 2000).

2.3. Leukaemia

Early studies reported in the previous IARC Monograph identified an unusually high prevalence of leukaemia and aplastic anaemia among shoe workers exposed to benzene in both Italy and Turkey (Aksoy et al., 1974, 1976; Vigliani, 1976; Vigliani & Forni, 1976; Aksoy & Erdem, 1978). An excess was also identified in the Italian cohort study where benzene exposures were reported to be very high until 1963 when regulations were changed (Paci et al., 1989; Fu et al., 1996). An excess of leukaemia was observed among workers in the Russian cohort compared to the general population, and all five were in the highest solvent-exposed group (Bulbulyan et al., 1998). All five of these cases were employed before 1960 when co-exposure to benzene was possible. No excess was observed in the updated English cohort (Fu et al., 1996). No excess of leukaemia was observed in the US cohort study (Lehman & Hein 2006). However, benzene was not detected in industrial hygiene surveys for the US study and “company management asserted that benzene had never been present in the solvents used at either of the plants.” No excesses were observed in the three US PMR studies. Andersen et al. (1999) also did not observe an excess in the Nordic Census to tumour registry linkage study. More recent case–control studies, including a large, multicentre Italian study with cases diagnosed during 1991–93, have not observed an excess risk for leukaemia associated with employment in the leather industries (Costantini et al., 2001; Forand, 2004; Terry et al., 2005).

2.4. Cancer of the bladder

An excess of cancer of the bladder was not observed in the updated British, Italian, or US cohorts (Fu et al., 1996; Lehman & Hein, 2006). A significant excess of cancer of the bladder was observed among women shoe workers (PMR, 2; P < 0.05) in Decouflé & Walrath (1983). However, no excess was observed among men. No excess of cancer of the bladder among either sex in another PMR study was found (Walrath et al., 1987). Pukkala et al. (2009) observed a slight excess in the Nordic Census to tumour registry linkage study (SIR, 1.08; 95%CI: 0.98–1.19).

Results for cancer of the bladder from 11 case–control studies are presented in Table 2.5. Two studies, both using broad definitions of leather work, observed strong evidence of an excess risk. Cole et al. (1972) observed an excess risk among leather-product workers. Schoenberg et al. (1984) observed an excess among men working with leather materials. Several studies observed very small excesses associated with leather work. Marrett et al. (1986) found a very weak association associated with leather dust. Schumacher et al. (1989) found very weak evidence of an excess risk associated with the leather industry, but not with leather dust. Kogevinas et al. (2003) observed a possible small excess among men from 11 European studies in a pooled re-analysis but ’t Mannetje et al. (1999b) observed a decreased risk among women from the same studies. Other studies either observed no risk or a decreased risk for cancer of the bladder among leather workers. Silverman et al. (1983) did not observe an excess among either leather products workers or shoe repairers in Detroit, USA. Silverman et al. (1989) did not observe an excess among either leather processing workers from ten regions of the USA. Siemiatycki et al. (1994) and Teschke et al. (1997) found no evidence of an association with leather or shoe work. Samanic et al. (2008) also did not observe an excess for cancer of the bladder associated with leather industry workers in Spain. [The Working Group noted that the results of Silverman et al. (1983) and Marrett et al. (1986) were not adjusted for smoking.]

2.5. Other cancers

Excesses of other cancers have been observed in some studies, but no consistent pattern has emerged (Decouflé & Walrath, 1983; Garabrant & Wegman, 1984; Walrath et al., 1987; Mikoczy et al., 1996; Bulbulyan et al., 1998).

2.6. Synthesis

There is consistent and strong evidence from both descriptive and case–control studies associating work in the boot and shoe industry with an increased risk of cancer of the nasal cavity and paranasal sinuses. Among those studies with histological classification of the tumours, very large excess risks were observed for sinonasal adenocarcinoma. When examined in case–control studies, the Brittish cohort study, and case series, this excess appears among workers with the highest leather dust exposure. There is strong evidence that exposure to leather dust causes cancer of the nasal cavity and paranasal sinuses.

Clusters of leukaemia cases were reported among workers with benzene exposure in the shoe industries of Italy and Turkey in the 1970s. An excess was also observed in an Italian cohort study and among a subgroup of a Russian cohort where benzene exposure was likely to have occurred. A case–control study in Italy did not observe an excess in the industry after changes in industrial practices resulted in large reductions in benzene exposure. Benzene is already recognized as a cause of leukaemia, and is likely to be the explaination of the previous excess observed in the industry.

Several early studies reported an excess risk of bladder cancer among leather workers. Two case–control studies observed an association with the leather industry, but many more recent studies found little or no association with the leather industry when tanning was not considered. For other cancer sites, no consistent pattern of excess risk was observed or too little data was available to adequately assess causality with boot and shoe manufacturing.

3. Cancer in Experimental Animals

No data were available to the Working Group.

4. Other Relevant Data

See Section 4 of the Monograph on Wood Dust in this Volume.

5. Evaluation

There is sufficient evidence in humans for the carcinogenicity of leather dust. Leather dust causes cancer of the nasal cavity and paranasal sinuses.

No data in experimental animals for the carcinogenicity of leather dust were available to the Working Group.

Leather dust is carcinogenic to humans (Group 1).


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