Skin sensitisers (Sh)
The list of sensitising substances is reproduced in Section B of Additional file
1. From a total of 143 sensitising substances at least 100 may cause skin sensitisation. Annual production estimates of substances associated with skin sensitisation (Sh) are quite large. They range between 1 to 10 million (2 substances), 0.1 to 1 million (4 substances), 10 to 100 K (17 substances), and 1 to 10 K tonnes per annum (16 substances). Sh substances are used in a wide variety of industrial applications, particularly in (i) the rubber industry as antioxidants, accelerators, and vulcanization agents, (ii) the production of dyes, epoxy resins, textiles and paints, (iii) the cosmetic, food and pharmaceutical industry, and (iv) the production of herbicides, fungicides and other pesticides. The large number of Sh substances and the wide variety of industrial settings associated with increased exposure to skin sensitisers explain the fact that technicians and operators (ISCO categories 3 and 8) can be potentially exposed to at least 106 different Sh substances. Concerning the remaining ISCO categories it was found that agricultural workers (ISCO 6), service workers (ISCO 5), professionals (ISCO 2), workers in elementary occupations (ISCO 9), craft workers (ISCO 7), armed forces workers (ISCO 0), and clerks (ISCO 4) may be exposed to at least 21, 21, 16, 11, 10, 7 and 1 skin sensitising substances, respectively (see Table
2).
A large body of epidemiological evidence on skin diseases in some European countries indicates that most of all occupational skin diseases (OSD) are due to irritant or allergic contact dermatitis (ICD and ACD, respectively) localised mostly on the hands and face [
36]. ICD is commonly associated with frequent use of water, soaps and detergents, alkalis, acids, metalworking fluids, organic solvents, petroleum products, oxidising or reducing agents, animal products or physical factors such as friction [
37]. On the other hand, the most common substances associated with occupational ACD are biocides, chromate, dyes, epoxy resins, fragrances, formaldehyde, (meth)acrylates, nickel, plants and woods, and rubber-processing chemicals [
37]. The overall incidence rates of OSD across occupational groups have been estimated for several European samples. The incidence of OSD in Northern Bavaria (Germany) between 1990 and 1999 have resulted in 6.7 cases per 10000 workers [
38]. In France, the incidence estimates from 2004 to 2007 was 1.5 per 10000 salaried workers [
39], whereas in Spain, the incidence of registered OSD for the year 2006 was 0.7 per 10000 workers [
40]. Since available incidence estimates depend on national legislation concerning reporting schemes of OSD and divergent compensation criteria, it has been acknowledged that incidence of OSD is being actually underestimated [
36].
The incidence of OSD across occupational groups is rather consistent and corresponds to the increased exposure risks of specific occupational groups. Hairdressers and barbers show the largest incidence of OSD both in Germany and the UK with 97.4 and 11.6 cases per 10000 workers, respectively, followed by bakers and printers [
38,
41]. Other occupational groups in those two countries showing large incidence rates are workers in the metallurgical industry (electroplaters, machine tool operatives, metal processors, machine setters and operators), the construction industry (tile setters, terrazzo workers, painters, brick layers, cement workers) the food industry (cooks, catering assistant), and the health care sector (dental nurses, dental technicians, nurses) [
38,
41]. A similar pattern of incidence of OSD can also be observed in France for the period 2004–2007. The highest incidence rates per 10000 workers were observed in the metallurgical industry (1.22), the construction industry (5.29), the chemical and rubber industry (1.97), and the services activities including hairdressers and household workers (1.87) [
39]. Regarding the prevalence of OSD, the EU-OSHA 2008 report indicates that the proportion of OSD is highest among craft workers (ISCO 7, 33%), followed by workers in elementary occupations (ISCO 9, 22%), operators (ISCO 8, 14%), and service workers (ISCO 5, 18%) [
42].
Although research on societal costs of occupational skin diseases is rather limited, the direct and indirect costs of occupational hand eczema in Germany have been estimated in a study conducted in 2013 by Diepgen and colleagues [
43]. The annual direct and indirect costs of occupational hand eczema per worker diagnosed and treated were on average 2646 EUR (95% CI 2265–3027 EUR) and 6152 EUR (95% CI 4508–7797 EUR), respectively. In Italy, the societal costs of severe chronic hand eczema refractory to standard therapy amounted in average to 5016 EUR per person-year (min. 411 EUR, max. 27648 EUR) [
44]. Additional costs may also occur in cases of occupational retraining, job change, or adverse psychosocial effects [
36]. Moreover, since for severe OSD more than a half of all cases may become persistent [
37], that is, they develop a persistent dermatitis even after removal from exposure to causative agents [
45], both direct and indirect costs are expected to increase depending on the degree of disability.
Substances causing airway sensitisation (Sa)
From the 143 sensitisers in Section B of the Additional file
1 a total of 32 are associated with respiratory sensitisation. Interestingly, from these 32 sensitisers 17 are both skin and airway sensitisers (Sah). The available annual production estimates of substances causing respiratory sensitisation are not as large as the estimates of the skin sensitising substances. Annual production of Sa substances range from 0.1 to 1 million (1 substance), 10 to 100 K (3 substances), and 1 to 10 K tonnes per annum (4 substances). Sa substances are widely used in several industrial processes such as the production of plastics, paper, resins, textiles, cosmetics, dyes, and in the metallurgic and food industry. Sa substances include also biological agents such as animal hair or other materials derived from animals, and cereal flour dusts. Occupations at higher risk of developing allergic reactions to Sa substances are technicians and operators who might be exposed to at least 14 and 15 different Sa substances, respectively. Agricultural workers, craft workers, professionals and workers in elementary occupations may have increased exposure for at least 8, 2, 2, and 1 Sa substances (see Table
2).
Respiratory sensitisers are associated with several respiratory diseases including irritation of mucous membranes, asthma, chronic bronchitis, chronic obstructive pulmonary disease and rhinitis [
46,
47]. Asthma is one of the most frequent occupational diseases in Europe [
48]. Several epidemiological studies have estimated that occupational agents may account for about 5% - 25% of new asthma cases among workers of different industries [
49,
50]. In spite of the large health and socio-economic impact of occupational asthma, incidence and prevalence are still underestimated [
50‐
52]. Moreover, some studies have pointed out that the number of workers with pre-existing asthma may be even larger and experience a worsening of symptoms [
49]. For several European countries the incidence of occupational asthma per 10000 workers has resulted in 0.23 in Belgium (2000–02) [
53], 0.24 in France (1996–99) [
54], 0.32 in the United Kingdom (1992–97) [
55], 1.74 in Finland (1989–95) [
56] and 0.28 in Germany (2003) [
46].
Incidence rates estimates of occupational asthma from several European countries report an unequal distribution of cases across occupational groups. Assuming that genetic susceptibility is randomly distributed across occupational groups, the unequal distribution of occupational asthma cases is related primarily to (i) the presence or absence of a latency period of airway obstruction associated mostly with allergic (IgE mediated) or irritant-induced asthma, respectively, (ii) the agent to which workers are exposed (low- vs. high-molecular-weight > 5 kDa), (iii) the duration of exposure and the agent concentration [
57,
58].
In France, the United Kingdom, Sweden and Finland bakers and painters show the largest incidence rates per 10000 workers ranging from 6.8 in France to 44.8 for male bakers in Finland, and from 3.3 in France to 22.3 for male painters and lacquerers in Finland [
54‐
56,
59]. The excess risk for bakers can be explained by continuous airway exposure to high-molecular weight agents such as vegetal proteins in cereals, flours, or other protein additives, and enzymes used for controlling the production process (e.g.
α-amylase) [
58]. The excess risk for painters has been associated with low-molecular-weight diisocyanates used in the production of lacquers and spray paints (e.g. 1,6-hexamethylene diisocyanate (822-06-0) and 1,5-naphthylene diisocyanate (3173-72-6)).
In general, workers in the chemical, plastic and metallurgic industries are exposed primarily to low-molecular-weight agents such as metal compounds (e.g. platinum and nickel compounds, tungsten carbide, cobalt) and reactive chemicals (e.g. diisocyanates and anhydrides) which have extensive applications as resins, dyes, production of polyurethanes, adhesives, insulating foams, lacquers and metal alloys for welding. The risk for healthcare workers and cleaners is related to increased exposure to biocides (e.g. glutaraldehyde) and cleaning products (e.g. quaternary ammonium compounds [
60]), antiobiotics (e.g. penicilins, psyllium), and natural rubber latex [
61]. Dusts of different species of wood associated with occupational asthma (particularly Western red cedar
Thuja plicata) are the main exposure for sawmill workers, carpenters and related wood processing workers showing relatively large incidence rates [
62]. The fact that incidence estimates and occupations at high risk are rather similar for males and females in Finland suggests that the specific exposure mechanisms and the job tasks defined by each occupation should account for most of the gender differences observed [
56].
A further complication of exposure to airway sensitisers is the fact that the majority of workers diagnosed with occupational asthma also suffer from occupational rhinitis, an inflammatory disease of the nose characterised by nasal congestion, variable airflow limitation and/or hypersecretion after exposure to sensitisers at the workplace [
63]. Epidemiological data from France suggest that this relationship between occupational rhinitis and occupational asthma is especially frequent when high-molecular-weight sensitisers are involved [
64]. Despite being a common condition epidemiological data of occupational rhinitis is rather scarce. Some studies have reported larger incidence rates for occupational rhinitis than occupational asthma [
63]. Age-standardised rate ratios (SRR) of occupational rhinitis estimated with register data of Finland for the period 1986–91 identified furriers (30.0), bakers (22.0), livestock breeders (22.0), food-processing workers (13.0), veterinarians (11.0), agricultural workers (8.3) and assemblers of electronic products (7.7) as occupations at high risk [
65].
Occupational asthma has a poor prognosis; once a worker develops occupational asthma after a latency period the chances of recovery are small [
66]. It has been estimated that approximately 70% of workers diagnosed with occupational asthma show symptoms and airway hyperresponsiveness even several years after complete cessation of exposure [
67]. Even though complete avoidance of exposure to the allergen is considered the treatment of choice [
68], the socio-economic consequences for workers and society are large. Ayres and collegues [
69] estimated the direct and indirect costs of occupational asthma in the United Kingdom from data of the Survey of Work-related and Occupational Respiratory Disease (SWORD) [
69]. The average direct costs per annum per case range from £530 to £715, whereas the indirect costs range from £1525 to £1685. The total present value costs of an average case to society lies between £120000 and £130000 per annum. Assuming that about one-third of cases is not being diagnosed, the authors estimated that the total lifetime costs of new cases to society from all potential cases in 2003 could lie between £95 and £135 million. Moreover, further analyses revealed that about 49% of the present value total costs are borne by the individual, 48% by the state and only 3% by the employer.