Work-related cancer

From OSHWiki
Jump to: navigation, search



Klaus Kuhl, Lothar Lißner, Kooperationsstelle Hamburg IFE GmbH, Germany

Introduction

According to Eurostat, over 30 million tonnes of carcinogenic, mutagenic and reprotoxic substances (CMRs) are produced in Europe annually.[1] As well as chemicals, there are biological agents, and physical/organisational factors which can cause cancer. Some typical work-related cancers (e.g. lung cancer and mesothelioma) have a high mortality rate. The disease is generally associated with a rapid onset of disability and a high degree of suffering. The high number of workers exposed has led to calls for coordinated action to protect workers’ health and improve working conditions. This article will present the hazards and risks, as well as related preventive and control measures.


Definition and identification

Work-related cancer is caused or worsened by occupational agents, factors and conditions. Cancer is a so-called malignant neoplasm, a broad group of diseases involving unregulated cell growth. Cells divide and grow uncontrollably, forming malignant tumours, and invade nearby parts of the body. The cells may also spread to more remote parts of the body through the lymphatic or blood system. Any human organ can be affected, and there are over 200 different known cancers.[2]

The mechanisms causing and influencing the carcinogenic process are still poorly understood. However, three types have so far been classified: a) mutagenesis (i.e. damaging the genome, the DNA, or causing similar so called epigenetic alterations, for example epigenetic silencing of tumour suppressor genes and activation of oncogenes), b) promoting cell proliferation, and c) promoting the progression to malignancy by somatic and/or genetic changes. The first type can take a long time before being diagnosed, while the others may manifest earlier.[3] In the first case, no threshold is assumed (further explanations below).

The methods to identify work-related cancers include epidemiological studies, animal (in vivo) studies, in vitro experiments and so-called in silico calculations (see below). In the 18th century, Percivall Pott was the first to describe occupational cancer in chimney sweepers caused by soot. [4] He carefully analysed the working conditions of his patients, following the example of Bernardino Ramazzini - the so called ‘Father of occupational medicine’ who laid its foundations in the 17th century. [5] Up to the 1970s, most recognised human carcinogenic factors were found primarily in the occupational environment. Human carcinogens that were first identified in this setting were chemicals such as arsenic, asbestos, benzene, chromium, nickel, radon, and vinyl chloride.[6] In 1926, Muller discovered a clear connection between x-rays and lethal mutations, widening the scope to physical factors.[7]

When one considers the rapid rate at which new chemicals are put on the market and working conditions are changing in combination with the long latency periods for cancer to develop, then it is clear that epidemiological studies must be complemented by other methods, to provide information more rapidly, e.g.:

  • Animal studies; to limit the number of animals (due to ethical considerations), a fairly high dosage is normally used, leading to problems in extrapolating to low doses and defining safety factors. Due to limited knowledge, the empirical models of the mathematical extrapolation procedure, do not reflect the underlying mechanisms for carcinogenicity, thus leaving a large uncertainty.[3]
  • In vitro methods; can be used to study the influence of substances on the DNA sequence of a gene and any gene products (mutagenicity). Additional evidence may be provided by results of studies of absorption and metabolism, physiology, and cytotoxicology.
  • In silico methods; e.g. computer simulations that combine information on identified toxicants of a similar structure, have been used to establish so-called quantitative structure-activity relationships (QSARs), thus allowing to anticipate possible effects based on the structure of a substance. These require a large amount of data and have so far been mainly used to prioritise the testing of chemical substances.

Boffeta and colleagues note that only a relatively small number of chemical exposures have been investigated with respect to the presence of a carcinogenic risk.[8]

For a long time, testing was seen as a responsibility of governments, but REACH, the EU Regulation No 1907/2006 for Registration, Evaluation, Authorisation and Restriction of Chemicals has shifted the responsibility to companies that develop or market chemicals. This will certainly improve the general situation on data availability. However, there are no epidemiological tests required, and testing requirements are regulated according to the tonnage, i.e. the annual tonnage produced or imported of each chemical by producer/registrant. More information is given in the Legislation chapter below.

In the context of this article, a carcinogen means any risk factor or condition that could cause cancer or contribute to its development, including physical, biological, organisational, and psychosocial factors.


Hazards and risks

The International Agency for Research on Cancer (IARC) classes substances into one of the following groups: carcinogenic (group 1), probably carcinogenic (group 2A), possibly carcinogenic (group 2B), not classifiable (group 3), and probably not carcinogenic (group 4).[9] [6] Evaluations of the IARC monographs show that occupational factors represent a high percentage of factors classified as Sufficient, Probable, and Possible human carcinogens.[10] The European Union classification of carcinogens is contained in the CLP (classification, labelling and packaging) Regulation (CE) 1272/2008, in line with the Globally Harmonized System (GHS) scheme. It consists of category 1: substances known (1A) or presumed (1B) human carcinogens, category 2: suspected human carcinogens.[11]

Biologic factors

Biological agents may cause cancer, either by causing health effects directly (hepatitis) or via toxic substances that they produce (e.g. aflatoxins, which are amongst the most potent poisons). Ochratoxin A, a toxin produced by Aspergillus ochraceus, Aspergillus carbonarius and Penicillium verrucosum, is one of the most-abundant food-contaminating mycotoxins. An exposition is possible during bulk handling of agricultural foodstuff (nuts, grain, corn, coffee), animal-feed production, brewery/malts, in waste management, composting plants, food production, and horticulture.[12] [13]

New and emerging risks

Besides chemicals, ionising radiation, and biologic factors many more factors and conditions have been identified that could cause cancer, as is explained in the following sub-chapters.

Endocrine disrupting compounds (EDCs)

Scientists have recently focussed on a different type of carcinogenic chemical: in February 2013, the United Nations World Health Organization (WHO) and the Environment Programme (UNEP) published a report on endocrine disrupting compounds (EDCs). The authors identified emerging evidence between exposure to EDCs and an increase in cancers such as breast, endometrial, ovarian, testicular, prostate, and thyroid, noting that these cancers have been increasing over the past 40-50 years.[14] The authors mention causes of prostate cancer, e.g. occupational exposure to pesticides, PCBs (polychlorinated biphenyls), and arsenic.

Nanomaterials

As regards nanomaterials, an EU-OSHA literature review stated that long-term animal studies with intratracheal instillation - performed with nanostructured carbon black, aluminium oxide, aluminium silicate, titanium dioxide (hydrophilic and hydrophobic) and amorphous silicon dioxide - resulted in tumours, induced by all tested nanomaterials. Micro-sized fine particles also caused tumours, but the potency of the nanomaterials was calculated as five - tenfold higher (volume basis).[15] Some types of carbon nanotubes may lead to asbestos-like effects.

Work organisation

Work organisational factors may also cause cancer, according to the Nordic Occupational Cancer Study (NOCCA) - a large cohort study based on the follow-up of the entire working populations in censuses in Denmark, Finland, Iceland, Norway and Sweden. Socioeconomic status (and, thereby presumably, lifestyle) was described as a risk factor for skin melanoma.[16]

Shift work and night work

Shift work and night work (as well as sedentary work) have recently been found to be potentially carcinogenic. Shift workers suffer from a disruption of the sleep–wake rhythm, insomnia and a lack of melatonin. Exposure to light at night, including a disturbance of the circadian rhythm, possibly mediated via the melatonin synthesis and clock genes, has been suggested as a contributing cause of breast cancer. Since shift and night-time work are prevalent and increasing in modern societies, persons who engage in night shift work may exhibit altered night-time melatonin levels and reproductive hormone profiles that could increase the risk of hormone-related diseases, including breast cancer. Any measure that helps regulate the melatonin levels may help to reduce these effects. According to the IARC monographs, eight studies reported relative risk estimates for histologically confirmed breast cancer for female nightshift workers, with vastly differing definitions of shift work in each study.[17]

Sedentary work

Boyle and colleagues conducted a population-based case-control study of colorectal cancer in Western Australia in 2005-2007 and found that long-term sedentary work may increase the risk of distal colon cancer and rectal cancer (tumours that develop in the large intestine).[18] A German study revealed an increased risk of testicular cancer for technicians and related professionals and clerical support workers. The authors noted that this could be related to socioeconomic status or sedentary life style, two factors that were identified in previous studies. However, missing occupational data and the choice of cancer controls represent challenges to the validity of this approach.[19]

Stress

In a 2003 literature review, Fox concludes that stress – regardless of type, severity or exposure duration - has little or no effect on later cancer incidence. He continues that it is reasonable to suggest that the same results apply in the work situation. As for cancer prognosis, too few studies have been done to draw any conclusions, even tentative ones, about stressors. It is, however, possible that strong social support may slightly decrease incidence, and perhaps increase survival.[20] However, it has to be noted that stress coping strategies may lead to increased smoking, drinking, eating, and use of drugs, and thereby increase the risk of cancer.

Heat shock

There is some evidence that heat shock leads to DNS (deoxyribonucleic acid) damage and cells can switch to high mutation rates for several cell generations (Fabre and Roman cited in[21]).

Non-ionising radiation

As has been mentioned above ionising radiation was among the first carcinogens that have been identified. However, also non-ionising radiation has come into the focus of scientists. Clapp and colleagues described new evidence in a 2007 study on environmental and occupational causes of cancer. Despite weaknesses in some individual studies, they concluded that recent publications had strengthened the evidence linking specific exposure with increased risk of cancer, among them brain cancer from exposure to nonionizing radiation, particularly radiofrequency fields emitted by mobile telephones.[22]

Overview

From the IARC documents, Siemiatycki and colleagues established a list of occupational carcinogenic factors, developing and applying the following rule: a factor was considered as occupational exposure if significant numbers of workers had been exposed at significant levels.[6]

Table 1: Overview of OSH relevant carcinogenic factors and conditions

Group Subgroup Example
Chemicals Gases Vinyl chloride

Formaldehyde

Liquids, volatile Trichloroethylene,

tetrachloroethylene, methylchloride, styrene, benzene, xylene

Liquids non-volatile Metalworking fluids,

mineral oils, hair dyes

Solids, dust Silica,

wood dust, talc containing asbestiform fibres

Solids, fibres Asbestos

Man-made fibres, e.g. ceramic fibres

Solids Lead,

nickel compounds, chromium VI compounds, arsenic, beryllium, cadmium, carbon black, bitumen

Fumes, smoke Welding fumes

Diesel emissions Coal-tar fumes, bitumes fumes, fire-, combustion emissions, PAHs, tobacco smoke

Mixtures Solvents
Pesticides Halogenated organic compounds DDT,

ethylene dibromide

Others Amitrole
Pharmaceuticals Antineoplastic drugs MOPP (a combination chemotherapy regimen used to treat Hodgkin's disease: Mustargen, Oncovin, Procarbazine, Prednisone) and other combined chemotherapy including alkylating agents
Anaesthetic gases
Biological factors Viruses Hepatitis B,

hepatitis C

Fungi producing mycotoxins Ochratoxin A (toxin produced by Aspergillus ochraceus, Aspergillus carbonarius and Penicillium verrucosum) one of the most-abundant food-contaminating mycotoxins
A. flavus, A. parasiticus from Aflatoxin (A1)
P. griseofulvum Griseofulvin (Kat 2B)
A. ochraceus, A. carbonarius, P. verrucosum Ochratoxin A (Kat. 2B)
A. versicolor, Emericella nidulans, Chaetomium spp., A. flavus, A. parasiticus Sterigmatocystin (Kat. 2B)
Physical factors Ionising radiation Radon

X-rays, cosmic radiation

Ultraviolet radiation (UV) Solar radiation,

artificial UV

Electromagnetic fields Mobile phone radiation,

MRI - Magnetic Resonance Imaging

Ergonomics Sedentary work
Contributing factors Work organisation Shift work,

night work

Life style factors Stress related obesity, smoking, drinking, drugs consumption
Emerging factors Nanomaterials Nano-tubes
EDCs – Endocrine Disrupting Compounds Certain pesticides,

certain flame retardants

Mixtures of various factors Chemicals and radiation Methoxsalen and UV A radiation
Work organisation and chemicals Shift work and solvents

Source: Compiled by the authors, adapted from [6] [22] [23] [8]

Boffetta and colleagues note that the current understanding of the relationship between occupational exposures and cancer is far from complete. Only a limited number of individual factors are established occupational carcinogens. For many more, no definitive evidence is available, based on exposed workers. However, in many cases, there is considerable evidence of increased risks associated with particular industries and occupations, although often no specific agents or conditions can be identified as aetiological factors.[8] See the following table 2.

Table 2: Occupations or industries that have been evaluated by IARC as definitely (group 1), probably (group 2A), or possibly (group 2B), entailing excess risk of cancer among workers.

Occupation or industry Suspected substance(s) Sites
Aluminium production Pitch volatiles; aromatic amines Lung, bladder
Arsenical insecticides production and packaging Arsenic compounds Lung
Auramine manufacture 2-Naphthylamine; auramine; other chemicals; pigments Bladder
Battery manufacture Lead compounds, cadmium and cadmium compounds Respiratory and digestive systems, prostate
Beer brewers Alcohol consumption Upper aero-digestive tract
Beryllium refining and machining; production of beryllium-containing products Beryllium and beryllium compounds Lung
Boot and shoe manufacture and repair Leather dust; benzene and other solvents Leukaemia, nose, paranasal sinuses, bladder
Butchers and meat workers Viruses, PAH Lung
Ceramic and pottery workers Crystalline silica Lung
Coal gasification Coal-tar; coal-tar fumes; PAHs (polycyclic aromatic hydrocarbons) Skin (including scrotum), bladder, lung
Coke production Coal-tar fumes Skin (scrotum), lung, bladder, kidney
Dry cleaning Solvents and chemicals used in “spotting”
Electricity: generation, production, distribution, repair Extremely low frequency magnetic fields

PCBs

Leukaemia, brain tumours

Liver, bile ducts

Electroplating Chromium (VI) compounds

Cadmium and cadmium compounds

Lung, sinonasal

Lung

Epichlorohydrin production Epichlorohydrin Lung, lymphatic and haemopoietic system
Ethylene oxide production Ethylene oxide Lymphatic and haemopoietic system (leukaemia), stomach
Farmers, farm workers Not identified Lymphatic and haematopoietic system (leukaemia, lymphoma)
Fishermen UV radiation Skin, lip
Flame retardant and plasticizer use Polychlorinated biphenyls Nasopharynx, sinonasal
Furniture and cabinet making Wood dust Nose and sinonasal cavities
Gas workers Coal carbonization products, 2-naphthylamine Lung, bladder, scrotum
Glass workers (art glass, container and pressed ware) Arsenic and other metal oxides, silica, PAH Lung
Hairdressers and barbers Dyes (aromatic amines, amino-phenols with hydrogen peroxide); solvents; propellants; aerosols Bladder, lung, non-Hodgkin lymphoma, ovary
Hematite mining, underground with radon exposure Radon daughters; silica Lung
Iron and steel founding PAHs; silica; metal fumes; formaldehyde Lung
Isopropanol manufacture, strong-acid process Diisopropyl sulphate; isopropyl oils; sulphuric acid Paranasal sinuses, larynx, lung
Magenta manufacture Magenta; ortho-toluidine; 4,4´-methylene bis(2-methylaniline); ortho-nitrotoluene Bladder
Mechanics, welders, etc. in motor vehicle manufacturing PAH, welding fumes, engine exhaust Lung
Medical personnel Ionizing radiation Skin, leukaemia
Painters Not identified Lung, bladder, stomach
Petroleum refining PAHs Bladder, brain, leukaemia
Pickling operations Inorganic acid mists containing sulphuric acid Sinonasal, lung
Printing processes Solvents; inks; oil mist Lymphocytic and haemopoietic system, oral, lung, kidney
Roofers, asphalt workers Polycyclic aromatic hydrocarbons Lung
Pulp and papermill workers Not identified Lymphopoietic tissue, lung
Railroad workers, filling station attendants, bus and truck drivers, operators of excavating machines Diesel engine exhaust

Extremely low frequency magnetic fields

Lung, bladder

Leukaemia

Rubber industry Aromatic amines; solvents Bladder, stomach, larynx, leukaemia, lung
Synthetic latex production, tyre curing, calendering operatives (calendering is a finishing process used on cloth), reclaim, cable makers Aromatic amines Bladder
Textile manufacturing industry Textile dust in manufacturing process; dyes and solvents in dyeing and printing operations Bladder, sinonasal, mouth
Vineyard workers using arsenic insecticides Arsenic compounds

UV radiation

Lung, skin

Skin, lip

Source: Established by the authors, adapted from [6] [8]

Kogevinas and colleagues combined data from 11 case control studies conducted in Europe between 1976-1996, and found that metal workers, machinists, transport equipment operators and miners are among the major occupations afflicted by occupational bladder cancer in men in Western Europe. In this population, one in 10 - 20 cancers of the bladder can be attributed to occupation.[24] In a similar project, Mannetie and colleagues found that a significant proportion of bladder cancer cases among European women (below the age of 65) were likely attributable to occupation (for the type of occupation see table 2, above).[25]

Many of the above-mentioned industries are in the manufacturing sector, as defined by the NACE system. More information on OSH issues in this sector can be found here: Manufacturing.

Boffetta and colleagues found that establishing and interpreting their lists was complicated by a number of factors[8]:

  1. Information on industrial processes and exposure is frequently poor, hindering a complete evaluation of the importance of specific carcinogenic exposure in different occupations or industries
  2. Exposure to well-known carcinogens, e.g. vinyl chloride and benzene, occurs at different intensities in different occupational situations
  3. Changes in exposure occur over time in a given occupational situation, either because identified carcinogenic agents are substituted by other agents or (more frequently) because new industrial processes or materials are introduced
  4. Any list of occupational exposure similar to the one Bofetta and colleagues have established can refer only to the relatively small number of chemical exposures which has been investigated with respect to the presence of a carcinogenic risk.

This illustrates the limitations of a classification, and, in particular, its generalisation to all workplaces; the presence of a carcinogen in an occupational situation does not necessarily mean that workers are exposed to it. Similarly, the absence of identified carcinogens does not exclude the presence of yet unidentified causes of cancer.

There has been much controversy regarding the proportion of cancers which are attributable to occupational exposure, given the fact that workers are also exposed to factors outside their workplaces. [26] Clapp and colleagues understand that cancer is ultimately caused by multiple interacting factors, as opposed to what they call ‘dubious attributable fractions’. Their new cancer prevention paradigm states that exposures are limited to avoidable environmental and occupational carcinogens, in combination with additional important risk factors, such as diet and lifestyle. [22]

While Bofetta and colleagues focus mainly on chemicals, it should be noted that these conclusions also apply to non-chemical carcinogens. For example, modern work patterns include a frequent change of workplace. This may also lead to changes in exposure to, e.g. ultraviolet radiation, electromagnetic fields, sedentary work, stress, etc. Exposure may also be more difficult to follow-up, as it may not be documented and/or companies may have closed down.

In general changes in the world of work may also increase the risk of exposure: increase in subcontracting, temporary work, multiple jobs, working at client’s premises with limited possibilities for adaptation, increasingly static work, move from industry to service sectors, increasing female employment in exposed occupations, atypical working times, multiple exposures, etc.

Occupational exposures

Sources of data on occupational exposure to carcinogenic agents, factors and conditions

There are three types of data sources:

  • National registers
  • Exposure information systems
  • Exposure measurements databases

Some countries have established national registers on exposure to selected carcinogens, which provide data on the number of exposed workers and their exposure. These registers include: The Finnish Register on Workers Exposed to Carcinogens (ASA Register), the Italian Information System for Recording Occupational Exposures to Carcinogens (SIREP), and the German ODIN Register, which collects information on workers who have been exposed to certain categories of carcinogens and are entitled to medical examinations due to their carcinogen exposure. Sources from other countries, such as Poland, Slovakia, and Czech Republic, are difficult to access for professionals from other countries because of language problems (see list in EU-OSHA report on cancer[27]).

There are also international and national exposure information systems on carcinogens, which are not based on notifications of exposed workers or workplace, but rather on estimations of the number of exposed workers and their level of exposure to selected carcinogens. For example, the International Information System on Occupational Exposure to Carcinogens (CAREX), set up in the 1990s, which includes estimates of exposure prevalence and the number of exposed workers in 55 industries for 15 EU Member States for the period 1990-93.[28] The major use of CAREX has been in hazard surveillance and risk/burden assessment. It has been updated in Finland with exposure level estimates (CAREX Finland, reported only in Finnish), Italy and Spain. New countries have been added to CAREX (Estonia, Latvia, Lithuania, the Czech Republic) and it has been applied to Costa Rica, Panama and Nicaragua (including pesticides). It has been modified for wood dust (WOODEX) with exposure level estimates for 25 member states of EU. CAREX Canada is currently under construction. CAREX has been used in the assessment of global burden of work-related cancers by WHO[29] and burden of occupational cancer in the United Kingdom[30] and other EU member states (SHEcan project, not publicly available).

Other exposure information systems, covering chemical agents, also include estimates and information on carcinogens. The above mentioned EU-OSHA report presents several examples, one of which is the Finnish Information System on Occupational Exposure (Finnish Job-Exposure Matrix, FINJEM), a database which covers a large selection of exposures, including carcinogens. FINJEM has also been useful for setting up other national job-exposure matrices for the Nordic Occupational Cancer study (NOCCA), e.g. in Sweden, Norway, Denmark and Iceland. Information on carcinogen exposure was also contained in the French SUMER survey , a survey among workers who undergo regular health surveillance by their occupational physicians (The Medical Monitoring Survey of Professional Risks), conducted in 1994, 2003 and 2010, which included national exposure data from COLCHIC. The COLCHIC database consolidates all occupational exposure data for chemicals collected in French companies by the Caisses Regionales d'Assurance Maladie (regional health insurance funds, CRAM) and the Institut National de Recherche et de Securite (national institute for research and safety, INRS).

Concentrations of carcinogens in the workroom air have also been measured. Data on the results of industrial hygiene measurements have been computerised in many countries (e.g. the German MEGA database of workplace measurements). Some of these sources also contain information on non-chemical carcinogens or suspected carcinogens (such as solar radiation, ionising radiation or radon, ultraviolet radiation, electromagnetic fields, hepatitis viruses, shift work including nightwork). Other sources include information about occupational exposure to carcinogens in worker groups who may be at higher than average risk of contracting occupational cancer due to their vulnerability (e.g. pregnant women) or higher than average exposure to carcinogens, e.g. young workers.[27]

Results on occupational exposure to carcinogenic agents, factors and conditions

The above mentioned report presents in detail the aggregated results of the above described data sources, listing the number of workers, the various substances or factors, the numbers exposed, the levels, the sectors, etc. Figure 1 presents an overview of exposures by frequency from one of the sources, the CAREX database.

Figure 1: The most common exposures (numbers of exposed workers) to agents covered by CAREX in 15 member states of the European Union in 1990-93

"Figure 1"
The most common exposures

Source: Kauppinen et al.[31]

According to the CAREX data, exposure to carcinogens at work is common among workers. The number of workers estimated as exposed in the early 1990s exceeded 30 million, which is over 20% of all employed workers. The most common among the exposures considered were ultraviolet radiation from sunlight (in regular outdoor work) and environmental tobacco smoke (ETS) in restaurants and other work places, whose contribution was about half of all exposures. Since the early 1990s, exposure to ETS at work has been substantially reduced due to prohibitions and other restrictions. Other relatively commonly occurring exposures which are likely to have decreased include lead, ethylene dibromide (additive of leaded gasoline), asbestos and benzene. The CAREX estimates (and other respective information systems) have not yet been validated. This has not been feasible due to the extremely large number of estimates and the lack of reliable alternative data. The re-evaluation of CAREX estimates via another approach suggests that CAREX estimates were mainly on the high side. However, in some cases, underestimation was also likely.[32]

Vulnerable groups

In CAREX Canada, men account for 74-93% of the most common carcinogenic exposures selected. Workers recorded on the Finnish ASA Register are predominantly men (80%).[33] According to French Matgéné estimations, men were more frequently exposed to seven agents, and women to only one (chloroform). In the French SUMER survey, the prevalence of exposure to the selected agents associated with cancer was 20% among men and 4% among women.[34] While this indicates that women are less frequently exposed to these carcinogens than men, some experts challenge these findings, arguing that there are groups whose occupational exposure to cancer risks and carcinogenic factors and conditions is underrepresented in exposure data, because the exposures considered are usually biased towards industrial occupations and towards exposures where measurements are available (e.g. there is less knowledge about exposure in service sector jobs).[23] According to the French SUMER survey of 2005, the prevalence of exposure among young workers (aged under 25) was slightly higher (17%) than the average rate (14%).[34] The 2010 SUMER survey established that workers in maintenance are particularly at risk of exposure to the carcinogenic agents considered in the survey, especially young workers in apprenticeship and subcontracted workers. Exposure is also higher in low qualified jobs.[35] [36] Before the prohibition of smoking in restaurants in Finland in 2005, many young workers (below 25 years) were exposed to environmental tobacco smoke, and most were women.[37]

Worker groups exposed to high levels of carcinogens can be identified in CAREX Canada, FINJEM, MATGENE, SUMER survey and WOODEX. Additionally, information on work tasks and occupations with high exposure to carcinogens can be found in exposure measurement registers, scientific articles and other reports. However, detailed data on exposure by occupation or work task is often so comprehensive that it is not published as such.

Finding the ‘worst’ carcinogen exposure is also a challenging task. Measurement data may be biased, estimates erroneous, and the carcinogenic potential of agents, factors and conditions can vary widely. [27] An Australian study published in 2013 surveyed workers and developed an automated expert exposure assessment system in order to make the assessment process more transparent and consistent. Workers were asked about their occupation and were attributed exposures linked to their work. The results showed that women are less exposed than men to the carcinogens under scrutiny (UVR, DEM, benzene, silica, wood dust, PAHs, ionising radiation, shift work, etc.). The authors noted some limitations of their study, including the lower proportion of younger and migrant workers in the sample compared to the general population, resulting in a potential under-representation of particular occupations and industries. [38]

Approaches to the assessment of occupational cancer by occupation

A comprehensive study was conducted in the Nordic countries - the Nordic Occupational Cancer Study (NOCCA). It is based on the follow-up of the whole working populations in one or more censuses in Denmark, Finland, Iceland, Norway and Sweden. It aim was to identify occupations and etiologic factors associated with cancer risks. A number of expected associations were observed, e.g. lip cancer with outdoor workers. New NOCCA findings that warrant further attention include cancer of the tongue and vagina among female chemical process workers, melanoma and non-melanoma skin cancer, breast cancer (among men and women), and ovarian cancer among printers; fallopian tube cancer among packers and hairdressers, penis cancer among drivers, and thyroid cancer among female farmers.[27] In Italy, the OCCAM project (Occupational Cancer Monitoring) was conducted in collaboration between the Italian National Institute of Workplace Safety and Prevention ISPESL (Istituto Superiore per la Prevenzione e la Sicurezza sul Lavoro) and the Italian National Cancer Institute in Milan (Istituto Nazionale per lo studio e la cura dei tumori). The aim is to investigate occupational cancer risks by primary site, geographic area (province, region) and industrial sector. The surveillance approach is based on case-control studies where occupational histories of cases, obtained with an automatic linkage with social security files, are compared with those of healthy people.[27]

In a 2009 presentation, the EU-OSHA’s Takkala and Schneider noted that there are about 167,000 deaths annually in the EU-27 which are attributable to work. The figure is based on Finnish and EU-OSHA research and ILO estimates. It includes accidents and violence (5%) and cancer (57%), with a large proportion attributable to asbestos.[39]

Discussion

The information on the extent of exposure to carcinogenic agents, factors and conditions in Europe is seriously outdated.[27] The most comprehensive effort so far has been the CAREX project, as presented above. National registers on exposure to carcinogens exist in some countries. They do not cover all relevant carcinogens, and underreporting is very likely. Occasional, irregular and low exposures tend to be particularly underreported in these official registers. Workers on short-term and varying tasks may be left out of the reporting routines.

From the point of view of preventing occupational cancers, knowledge of the levels of exposure in different occupations, jobs and tasks is essential. Some review studies on specific occupations do exist, e.g. for hairdressers.[40] However, the long latency period between exposure and the manifestation of cancer makes it difficult to establish a) a clear link between exposure to a certain factor and the related cancer, and b) the recognition of a specific cancer as attributable to occupational exposure. This especially applies when carcinogenic factors are mixed, given the fact that workers are not usually exposed to just one factor, but rather various factors, e.g. combinations of chemicals and/or biological, physical, and work organisational factors and conditions.

Information systems should incorporate estimates of exposure levels, in order to better serve hazard surveillance, quantitative risk and burden assessment, and to set prevention priorities. Other useful improvements:

  • the inclusion of time dimension
  • better use of exposure measurement data in estimations
  • extension to all member states of EU
  • inclusion of gender-specific and occupation-specific estimates
  • inclusion of uncertainty information for the estimates.

Several of these improvements have been adopted in exposure information systems, such as WOODEX, TICAREX, Matgéné, FINJEM and CAREX Canada. The most developed model at the moment is probably CAREX Canada, which has most of these features, and disseminates information on exposures and risks through an informative, easy-to-use and free web application. Updates and extensions would be very helpful in developing informed policy decisions and priority setting. CAREX Canada is also part and parcel of a policy including intervention research, in order to identify the most appropriate measures to prevent occupational cancer risk in practice. The re-evaluation of the most relevant estimates (e.g. those indicating high exposure and those of large industries or occupations) can likely increase the validity of results. It is also worth noting that a great deal of estimates in CAREX and other exposure matrices is based on ‘expert judgment’. Empirical data on the prevalence and exposure level is only used if easily available. Although measurement data is available, expert judgment is required to judge its representativeness and applicability to the occupations or industries to be assessed, which entails a subjective element. The validity of exposure estimates is likely to increase in the future as more measurement data becomes available in computerized form, and the Bayesian methods to combine measurement data and expert judgements become more widely used. The method of automated expert assessment, employed by the Australian study mentioned above, seems to be a promising way of overcoming some of these limitations.[38] The possibilities provided by approaches such as NOCCA and OCCAM to analyse cancer risks by occupation based on cancer registries and case histories and by occupational exposure should be fully utilized.


Legislation, policy

ILO convention

The ILO (International Labour Organization) convention C139 on occupational cancer was adopted in 1974. Some European Member States have not yet ratified the convention, including Austria, Bulgaria, Estonia, Greece, Latvia, Lithuania, Romania, and the United Kingdom. The ILO requests governments to[41]:

  • frequently determine carcinogenic agents/factors (not restricted to chemicals and including factors that develop in the course of work processes), using latest findings
  • make every effort to replace carcinogenic agents/factors by harmless or less harmful ones
  • generally prohibit work under exposure of such factors; exceptions may be granted, as specified below
  • grant exceptions only under very strict conditions, including:
    • the issue of a certificate specifying in each case the protection measures to be applied
    • the medical supervision or other tests or investigations to be carried out
    • the records to be maintained
    • the professional qualifications required of those dealing with the supervision of exposure to the substance or agent in question.
  • implement a tight medical supervision, also after the cessation of the worker’s assignment
  • specify levels as indicators for surveillance of the working environment, where appropriate

EU Workplace legislation

The principles of the framework Directive and its daughter Directives apply to all of the risk factors described in section 3 of this article. There are a number of specific Directives for the factors identified here, amongst which there is also the Directive for biological agents, which governs workplace protection from biological agents.

As well as the Directives on radiation and nuclear safety, and biological agents the main piece of legislation on carcinogenic agents is the Directive 2004/37/EC of 29 April 2004 on the protection of workers from the risks related to exposure to carcinogens or mutagens at work. It defines a clear hierarchy of specific control measures, details information and consultation of workers, and defines record-keeping. Its aim is the protection of workers against risks to their health and safety, including the prevention of risks arising or likely to arise from exposure to carcinogens or mutagens at work.[42] The directive requests Member States to establish arrangements for health surveillance of workers if there is a risk for health and safety (prior to exposure, at regular intervals thereafter). If a worker is suspected of suffering ill-health due to exposure, health surveillance of other exposed workers may be required, and the risk shall be reassessed. Individual medical records of health surveillance shall be kept.

A revision of the Directive has been pending since 2004. In 2012, the European Advisory Committee for Safety and Health at Work (ACSH) suggested adding ten new occupational exposure limit values (OELV) to an updated directive, namely for crystalline silica, refractory ceramic fibres, chromium VI and trichloroethylene, hydrazine, acrylamide, epichlorohydrin, 1,2-dibromoethane, methylenedianiline (MDA) and wood dust (updating an existing OELV). The European trade union institute (ETUI) expressed hope that this proposal would accelerate the rather slow pace of the directive’s revision.[43] The SHEcan project has studied the impact of possible amendments to the directive, such as revising some of the OELs and introducing OELs for a range of additional substances. The results of SHEcan study have been reported to the European Commission, but not yet published in scientific literature. The SHEcan study is unique because it assesses both health effects (burden of disease) of occupational exposure and extends its scope to socioeconomic and environmental consequences of exposure, and the European regulations on exposure.[27]

Binding occupational exposure limit values are listed in the Directives 98/24/EC, 2003/18/EC, 2004/37/EC and 2009/148/EC. They are established for a limited number of chemical substances: asbestos: actinolite, grunerite, anthophyllite, chrysotile, crocidolite and tremolite, benzene, lead and inorganic lead compounds, hardwood dusts and vinyl chloride.

When establishing occupational exposure levels (OELs), a distinction is made by some countries and their expert committees between genotoxic and non-genotoxic mechanisms of action. The US Environmental Protection Agency (EPA) default assumption for all substances showing carcinogenic activity in animal experiments is that no threshold exists (or at least none can be demonstrated), so there is some risk with any exposure. This is commonly referred to as the non-threshold assumption for genotoxic (DNA-damaging) compounds. Some EU member states do make a distinction between the two. For genotoxic carcinogens, quantitative dose-response estimation procedures are followed that assume no threshold. For the other substances, it is assumed that a threshold exists, and dose-response procedures are used that assume a threshold. In the latter case, the risk assessment is generally based on a safety factor approach, similar to the approach for non-carcinogens. [29] For more information on the SCOEL (Scientific Committee on Occupational Exposure Limit Values) OEL procedure see for example the presentation of Popischil:[44] or the documentation of the European Commission[45].

For substances for which no safe threshold can be established, there is an obligation in many countries to make every effort to reduce concentrations to the lowest possible level, in cases where the substances cannot be avoided. Other countries are developing exposure limits based on the concept of tolerable/acceptable risk, usually in the range of 10-2 to 10-5 cases of cancer ,depending on whether the risks concern the frequency of changes in health status during the year, or over a lifetime. This corresponds with an average risk of sustaining a fatal accident[46] [47] [48]. In the Netherlands, OELs are set at a level of excess cancer death of 10-6, but this value must be underscored when possible.[49]

In a 2008 EU-OSHA survey on OELs for CMR substances, nine out of 20 EU countries outlined difficulties in determining OELs for CM substances - most commonly the lack of national exposure and toxicological data, and problems reaching a consensus.[49]

The authors of a DG EMPL evaluation study calculated if appropriate action would be taken concerning carcinogens for which no occupational exposure limit (OEL) currently exists and others for which the OEL could be reduced, this could prevent more than 100,000 occupational cancer deaths in the EU-27 over the next 60 years.[50]

There may also be problems in measuring concentrations at workplaces (e.g. equipment too large / difficult to handle). Measuring methods may not yet be developed, and often workers are exposed various mixtures of chemicals or factors, e.g. solvents and welding fumes, and welding fumes, stress, and electromagnetic fields. For psychosocial conditions, such as shift work, safe levels cannot be determined yet.


REACH

While registration under REACH will improve the overall quality of the database on substance hazards, the aspect of tonnage is problematic, as REACH does not require data for chemicals produced in small quantities (less than 10 tonnes per year). However, the use of substances of high concern may not be permitted or may be subject to specific restrictions. Moreover, a number of chemical (e.g. non-intentional emissions) and non-chemical carcinogens do not fall under REACH. A study comparing OELs and DNELs found DNEL values well above or below OEL values. These discrepancies may create confusion in terms of legal compliance, risk management, and risk communication, although OSH regulations apply.[51]

Furthermore, REACH does not cover process generated substances, neither does it distinguish between micro and nano-sized particles of the same bulk chemical.

A threshold dose/concentration cannot be identified when it is known that genotoxicity is the underlying mechanism for the toxicity of a substance. In such cases, a DNEL value cannot be derived, and instead a qualitative risk characterisation approach is applied, which operates with more qualitative measures for the potency of the substance used for developing exposure scenarios with appropriate risk management measures (RMMs) and operational conditions (OCs). This approach is somewhat similar to the ALARA-principle (as-low-as-reasonably-achievable), originally used in the area of radiation protection.[52] In this case it is important to apply a precautionary principle when considering prevention measures.

In cases where there are no reliable exposure limits or measuring cannot be conducted, authorities must give clear and detailed guidance, as requested by the ILO, and workplace legislation, for reducing the risk to an acceptable minimum.

Compensation

Worker compensation systems are usually part of the social security schemes of the EU Member States. They were introduced to insure workers against the consequences of work-related injuries, and relieve employers from financial liability. The organisation, funding, coverage and membership details of each system are different. They also include compensation for acknowledged occupational diseases, A 2013 European Commission report lists the recognised cancers which are currently included in the EU schedule of occupational diseases.[53]


However, trade unions make the criticism that getting recognition of occupational diseases caused by carcinogens is often difficult in the European Union (EU).[54] There is also a lack of harmonized criteria to recognise occupational diseases.[53]

While improved recognition of asbestos-related diseases in occupational disease compensation systems is vital, there is also a good case to be made for establishing specific funds to provide better compensation for all victims (including self-employed workers, family members who have suffered exposure in the home, etc.). The track record of funds established in France and the Netherlands could be a model for other countries.[55] In France, OSH action plans have been integrated with action plans on cancer. In the Nordic countries, there are specific exposure registers, or cancer registers, and the integration of occupational cancers are integrated into in cancer registers.

Discussion

The ILO has set clear demands in the above mentioned convention. However, implementation in Europe is a slow process.

It often takes a long time before carcinogenic factors (especially non-chemical) are determined and accordingly regulated. For example. breast cancers caused by working conditions and skin cancer caused by UV radiation while welding are not recognised in the German law on occupational diseases, making it almost impossible for workers to get compensation. Denmark has introduced a system, where all factors identified by the IARC are almost automatically recognised as causes of an occupational disease.[56] [57]

The ILO demands that work under exposure of carcinogenic agents, factors and conditions is generally prohibited, but exceptions may be granted, e.g. with 'the issue of a certificate specifying in each case the protection measures to be applied'. This remains a big challenge.

Prevention and control measures

Prevention measures in companies and organisations have to rest on sound OSH management. Objectives, responsibilities, qualifications, training, and communication are important features of such a management system, which has to guarantee a comprehensive risk assessment and the implementation of related measures. The risk assessment should involve the affected workers as they have the practical knowledge of the working processes, the related conditions and the agents and factors in use. Preventive measures have to be derived, based on the assessment. However, as carcinogenic substances, agents, factors and conditions cover a wide and often disputed area, companies (especially smaller ones) are strongly advised to seek guidance from external experts, e.g. labour inspectors and occupational physicians. The specific measures to be selected depend firstly on the type of substance/factor: Chemical substances need different measures than biological, physical or psychosocial agents. Emerging risks, such as exposure to nanomaterials and endocrine disrupting compounds (EDCs), often require a precautionary approach. Clapp and colleagues demand a new cancer prevention paradigm, arguing that it should be based on an understanding that cancer is ultimately caused by multiple interacting factors, as opposed to a paradigm based on what they call ‘dubious attributable fractions’. This new cancer prevention paradigm demands that exposures are limited to avoidable environmental and occupational carcinogens in combination with additional important risk factors, such as diet and lifestyle.[22] The European Trade Union Institute ETUI came to a similar result, see: [58]. EU-OSHA recommends more focus being placed on changes in the world of work, such as increase in subcontracting, temporary work, multiple jobs, working at client’s premises with limited possibilities for adaptation, increasingly static work, move from industry to service sectors, increasing female employment in exposed occupations, atypical working times, and multiple exposures.[23]

Avoidance, substitution

The most effective measure is the avoidance of the dangerous agents, factors and conditions or the substitution by harmless ones. However, this can be very difficult in practice, especially in smaller companies. Studying hazardous chemicals, Ahrens and colleagues concluded that companies would rather implement technical and personal measures, but would disregard efforts to eliminate or reduce the hazards.[59] The authors found that efforts by companies meet a number of challenges:

  • Attitude: never change a running process, as process changes may bring about uncertainties
  • No priority either in companies or practical governance
  • Dealing with the current problems is already too laborious; no additional problems by an unnecessary innovative approach (existing standards etc.)
  • Uncertainty in risk assessment – a shift of risks may be possible
  • Substitutes are less tested in practice
  • Integration in the production chain necessitates an innovation beyond what the company can implement
  • Technological or economic difficulties

The authors have identified influential factors, such as society, public policy, regulation, market forces, etc. that all must play a role to overcome these difficulties. Some of these observations also apply to non-chemical carcinogens, e.g. avoidance or reduction of sedentary work in the office by using adjustable desks and appliances that allow work in a standing position at the desk ( dynamic workstations, treadmill desk).


Technical, organisational and personal solutions

Technical solutions include encapsulation and exhaust systems. However, systems can be damaged, may fail and need to be switched off for repair and maintenance. Organisational solutions, such as only allowing qualified workers to conduct the work and having strict supervision in place, are often relying on personal protective equipment (PPE). PPE often requires additional measures to increase safety. E.g. experts found that welders are often reluctant to use respirators, and workers sometimes deliberately turn off safety devices.[60] Promoting safe behaviour needs a comprehensive approach: management and supervisors have to set examples, there has to be a no-blame culture, and swift action on feedback proposals has to be demonstrated. The measures that aim to improve the safety behaviour of workers should include peer-observation and peer-discussion. All measures, including technical ones, have to be accompanied by proper instructions and training.

Examples of solutions

The sectors and job types also influence the measures to be selected, as do process scenarios, such as working in confined spaces, using varying amounts of substances at different temperatures, etc. The following table gives examples of the measures recommended in the examined literature, as well as possible tools, guidance, etc.

Table 3: Overview of preventive measures

Group Type of measures Examples
Chemicals General Agreed codes of practice e.g. the German TRGSses[61], sectoral guides
Avoidance, substitution with harmless agents Substitution databases and tools, e.g. SubsPort.eu, substitution-cmr.fr
Technical measures, incl. substitution with less hazardous agents Closed system, e.g. airtight metal cleaning plant using perchloroethylene, specific local extraction systems, examples from database Cleantool.org
Organisational measures Access system for specifically trained workers
Personal measures Respirators with specific filters
Pesticides Avoidance, substitution with harmless agents Organic farming
Technical measures, incl. substitution with less hazardous agents Integrated pest management,

using application procedures and devices that reduce exposure

Organisational measures Reducing the number of exposed, avoiding side-exposure of workers who are not applying pesticides, decontamination procedures, proper procedures for storage and cleaning of substances and equipment, maintenance of application devices, machinery and protective equipment
Personal measures PPE, protective clothing, hygienic procedures for separating and cleaning contaminated clothing
Pharmaceuticals General Best practice examples described in the Commission guideline for the health care sector[62]
Emerging factors, nanomaterials General Good practice examples at EU-OSHA website[63], precautionary approach needed
Avoidance, substitution with harmless agents Avoid, reduce

Substitution databases, e.g. SubsPort.eu, substitution-cmr.fr

Technical measures, incl. substitution with less hazardous agents Closed systems
Organisational measures Cordoning off of areas, restricted access
Personal measures Recommended respiratory protective equipment,

precautionary approach needed

Biological factors General Commission guideline for the health care sector[64],

specific measures for specific agents, e.g. matrix from NIOSH[65], agreed codes of practice, eg. TRBAs[66] [67]

Avoidance, substitution with harmless agents Only applicable where there is deliberate use of the biological agent, however, work procedures can be adapted to limit unintentional exposures and leaks
Technical measures, incl. substitution with less hazardous agents Closed systems, engineering controls, capture at the source of emission

room ventilation and air-conditioning measures, binding dust using mist technique, enclosed transport routes for dust-producing bulk materials

Organisational measures Good hygiene practices,

cleaning and hygiene plan, restricted access, black/white areas, spatial separation of polluted and unpolluted areas

Personal measures PPE, proper clothing, vaccination
Physical factors Measures against sedentary work Avoidance, reduction of sedentary work by dynamic workstations and/or treadmill desks, organisation of work to avoid static work, prolonged standing and prolonged sitting, e.g. through breaks and reorganisation of work procedures
Measures against radiation Closed, insulated systems,

cordoning off of areas, restricted access, recommended personal protective equipment

Psychosocial factors Avoidance, substitution with harmless agents Reduction or avoidance of stress by beneficial social climate
Technical measures, incl. substitution with less hazardous agents Reduction of stress by optimal equipment and design of rooms
Organisational measures Improved work organisation (participation of workers)
Personal measures Training on stress coping methods, improving social climate,

health promotion, avoidance of negative stress coping strategies (smoking, drinking etc.)

Shift work, night work Technical and organisational Shift work design according to scientific recommendations and best practice examples,

design of schedules, limitation of years worked in shifts, health promotion, organisation of rest periods[68], rest and eating facilities, making available appropriate meals

Personal measures Training, instructions regarding eating habits and rest periods
Combination of different risk factors General Precautionary approach needed,

holistic risk assessment, job-exposure matrices that address all risks, approach by occupations

Source: Compiled by the authors

Guidelines and tools

Ideally, the risk assessment help offered to SMEs should be sector specific, covering all factors, such as chemicals, biologic agents, physical agents and psychosocial conditions. The web-based and interactive tools allow continuous update of the documentation. The measures proposed should also consider the precautionary principle when sufficient data is not yet available. An interactive tool is currently being developed by EU-OSHA (and several partners) - OiRA , Online Interactive Risk Assessment. This is, however, a huge task, and it will take time until such a tool is available for all sectors and in all member state languages.

SubsPort – European substitution portal

The SubsPort project views substitution of hazardous chemicals (including carcinogenic substances) as a fundamental measure for reducing risks to environment, workers, consumers and public health.The project has developed an internet portal that constitutes a state-of-the-art resource on safer alternatives to the use of hazardous chemicals. It includes guidance for substance evaluation and substitution management. Training on substitution methodology and alternatives assessment are also provided.

In 2013, the French National Cancer Institute (INCA) launched new tools for health professionals for the prevention of occupational cancers.

  1. Cancer Pro Actu (News) is a quarterly newsletter documentary on the prevention of occupational cancers. It presents a selection of tools and recently published Internet media (usually non-priced).[69]
  2. Cancers Doc Pro is a guide to resources on the primary prevention of occupational cancers. It offers a selection of practical tools and media that can be used by occupational health care professionals.[70]


Treatment, rehabilitation, back to work

More workers now return to work after cancer treatment, as a result of improved identification and treatment. However, EU-OSHA concludes that there are only a few targeted rehabilitation and return-to work strategies, and these were originally developed for other work-related health conditions (e.g. musculoskeletal disorders). Workers who have suffered work-related cancer may need specific measures to protect them from re-exposure to the same risks, or to adapt the conditions to their physical abilities. The first days after the return to work are crucial, so enterprises should be prepared to adapt working conditions to the specific conditions at an early stage. A thorough assessment of the current situation is needed. Cancer risk factors such as shift work are particular challenging for such workplace adaptation.[23]


Outlook

The changes in the world of work mean that OSH research and prevention should place more attention on such factors and conditions as:

  • Collection and use of empirical data on exposure to carcinogens. Reliable information on the extent and levels of exposure is the basis for effective prevention of occupational cancer risks.
  • Collection, analysis and dissemination of information on occupations and work tasks entailing high exposure. This kind of information is required to target preventive measures to workers at high risk.
  • Stress coping strategies may lead to increased smoking, drinking, eating and use of drugs
  • Changes in the world of work, such as increase in subcontracting, temporary work, multiple jobs, working at client’s premises with limited possibilities for adaptation, increasingly static work, move from industry to service sectors, increasing female employment in exposed occupations, atypical working times, and multiple exposures
  • Mixture effects
  • Emerging risks, such as EDCs and nanomaterials
  • Ergonomics and work organisation have been newly recognised as important for cancer prevention (e.g. reorganising sedentary work and night shift work)

A precautionary approach needs to be applied where risks are possible, and where the scientific data does not yet allow risks to be quantified, defined or measured. The authorities in collaboration with OSH research have to provide precise measures and related guidelines. The ILO Convention requests that exemptions from prohibition of using carcinogenic agents (including non-chemical factors/conditions and mixtures) may only be granted by issue of a certificate specifying in each case the conditions to be met. Improvements in enforcement and awareness raising are needed so that this requirement is applied much more thoroughly.


References

  1. Eurostat – The statistical office of the European Union, Production of toxic chemicals, by toxicity class, Total production of chemicals, 2011. Retrieved 10 February 2011, from: [1]
  2. Wikipedia – The Free Encyclopedia (2013). Cancer. Retrieved 20 October 2013, from: [2]
  3. 3.0 3.1 van der Heijden, C.A., 'Carcinogen risk assessment', ILO encyclopaedia, 2003. Available at: [3]
  4. Brown, J.R. & Thornton, J.L., 'Percivall Pott (1714-1788) and Chimney Sweepers' Cancer of the Scrotum', Occupational & Environmental Medicine (previously: British Journal of Industrial Medicine), 14,1 , 1957, pp. 68-70. Available at: [4]
  5. Franco, G. & Franco, F., 'Bernardino Ramazzini: The Father of Occupational Medicine', American Journal of Public Health, 91, 9, 2001, p. 1382. Available at: [5]
  6. 6.0 6.1 6.2 6.3 6.4 Siemiatycki, J., Richardson, L., Straif, K., Latreille, B., Lakhani, R., Campbell, S., Rousseau, M-C. & Boffetta, P., 'Listing Occupational Carcinogens', Environmental Health Perspectives, 112, 15, 2004. Available at: [6]
  7. Wikipedia (2013). Hermann Joseph Muller. Retrieved 1 March 2014, from: [7]
  8. 8.0 8.1 8.2 8.3 8.4 Boffetta, P., Saracci, R., Kogevinas, M., Wilbourn, J. & Vainio, H., 'Occupational carcinogens', ILO encyclopaedia, 2003. Available at: [8]
  9. IARC - International Agency for Research on Cancer (2013). Agents classified by the IARC monographs. Retrieved 28 October 2013, from: [9]
  10. Blair, A., Marrett, L. & Freeman, L.B., 'Occupational cancer in developed countries', Environmental Health, 10, Supplement 1, 2011. Available at: [10]
  11. Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 (Text with EEA relevance), Official Journal L 353, 2008, p. 0001 - 1355. Available at: [11]
  12. BAuA - Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (German federal agency for safety at work and occupational medicine), Bedeutung von Mykotoxinen im Rahmen der arbeitsplatzbezogenen Gefährdungsbeurteilung, Sachstandsbericht, 2007. Available at: [12]
  13. Heederik, D., Endotoxins: an emerging biological risk?, Presentation at the EU-OSHA Workshop 'Occupational risks from biological agents: Facing up the challenges', Brussels, 6-7 June 2007. Retrieved 31 March 2014, from: [13]
  14. WHO - World Health Organization & UNEP - United Nations Environment Programme, State of the Science of Endocrine Disrupting Chemicals 2012, edited by Bergman, A., Heindel, J.J., Jobling, S., Kidd, K.A. & Zoeller, R.T., Inter-Organization Programme for the Sound Management of Chemicals, 2012. Available at: [14]
  15. EU-OSHA - European Agency for Safety and Health at Work, Workplace exposure to nanoparticles, European Risk Observatory, literature review, Publications Office of the European Union, Luxembourg, 2009. Available at: [15]
  16. Martinsen, J.I., Kjaerheim, K., Lynge, E., Gunnarsdottir, H.K., Sparen, P., Tryggvadottir, L., Weiderpass, E. & Pukkala, E., 'Occupations and socioeconomic status as risk factors for skin melanoma', NOCCA Congress presentations and abstracts, 2008. Retrieved 23 February 2014, from: [16]
  17. IARC - International Agency for Research on Cancer, Shiftwork, Monographs, volume 98, 2010. Available at: [17]
  18. Boyle, T., Fritschi, L., Heyworth, J. & Bull, F., Long-term sedentary work and the risk of subsite-specific colorectal cancer, Am J Epidemiol., 2011 May 15;173(10), 2011, pp. 1183-1191. Available at: [18]
  19. Yousif, L., Hammer, G.P., Emrich, K., Blettner, M. & Zeeb, H., 'Occupational risk factors for testicular cancer: a registry-based case-control study in Rhineland Palatinate – Germany', German Medical Science, 12, 2013, Retrieved 31 March 2014, from: [19]
  20. Fox, B.H., 'Cancer', ILO encyclopaedia, 2003. Available at: [20]
  21. Cairns, J., ‘The possible prevention of cancer’, Environmental Health, 10, Supplement 1, 2011. Available at: [21]
  22. 22.0 22.1 22.2 22.3 Clapp, R.W., Jacobs, M.M. & Loechler, E.L., Environmental and Occupational Causes of Cancer - New Evidence, 2005-2007, A publication of the Lowell Center for Sustainable Production, 2007.
  23. 23.0 23.1 23.2 23.3 EU-OSHA - European Agency for Safety and Health at Work (2012). Workshop on carcinogens and work-related cancer. Retrieved 4 July 2013, from: [22]
  24. Kogevinas, M., 't Mannetje, A., Cordier, S., Ranft, U., González, C.A., Vineis, P., Chang-Claude, J., Lynge, E., Wahrendorf, J., Tzonou, A., Jöckel, K.H., Serra, C., Porru, S., Hours, M., Greiser, E., Boffetta, P., 'Occupation and bladder cancer among men in Western Europe', Cancer Causes Control, Dec;14(10), 2003, pp. 907-914. Available at: [23]
  25. Mannetje, A., Kogevinas, M., Chang-Claude, J., Cordier, S., González, C.A., Hours, M., Jöckel, K.H., Bolm-Audorff, U., Lynge, E., Porru, S., Donato, F., Ranft, U., Serra, C., Tzonou, A., Vineis, P., Wahrendorf, J., Boffetta, P., 'Occupation and bladder cancer in European women', Cancer Causes Control, June 10(3), 1999, pp. 209-217. Available at: [24]
  26. Pearce, N., Boffetta, P. & Kogevinas, M., 'Cancer - Introduction', ILO encyclopaedia, 2003. Available at: [25]
  27. 27.0 27.1 27.2 27.3 27.4 27.5 27.6 EU-OSHA - European Agency for Safety and Health at Work, Exposure to carcinogens and work-related cancer: A review of assessment methods, European Risk Observatory Report, Luxembourg: Publications Office of the European Union, 2014. Available at: [26]
  28. Kauppinen, T., Toikkanen, J., Pedersen, D., Young, R., Ahrens, W., Boffetta, P., Hansen, J., Kromhout, H., Maqueda Blasco, J., Mirabelli, D., de la Orden-Rivera, V., Pannett, B., Plato, N., Savela, A., Vincent, R. & Kogevinas, M., ‘Occupational exposure to carcinogens in the European Union’, Occ Environ Med 57, 2000, pp. 10-18.
  29. Driscoll, T., Nelson, D., Steenland, K., Leigh, J., Concha-Barrientos, M., Fingerhut, M. & Prüss-Üstün, A., ‘The global burden of diseases due to occupational carcinogens’, Am J Indust Med 48, 2005, pp. 419-431. Available at: [27]
  30. Rushton, L., Hutchings, S. & Brown, T., ‘The burden of cancer at work: estimation as the first step to prevention’, Occup Environ Med 65, 2008, pp. 789-800.
  31. Kauppinen, T., Toikkanen, J., Pedersen, D., Young, R., Ahrens, W., BoVetta, P., Hansen, J., Kromhout, H., Blasco, J.M., Mirabelli, D., de la Orden-Rivera, V., Pannett, B., Plato, N., Savela, A., Vincent, R. & Kogevinas, M., 'Occupational exposure to carcinogens in the European Union', Occup Environ Med, 57, 2000, pp. 10–18. Available at: [28]
  32. Cherrie, J., Van Tongeren, M., Semple, S., ‘Exposure to occupational carcinogens in Great Britain’, Ann Occup Hyg, 51, 2007, pp. 653-664.
  33. Saalo, A., Soosaar, A., Länsimäki, E. & Kauppinen, T., ASA 2010 (in Finnish), Finnish Institute of Occupational Health, Helsinki, 2012.
  34. 34.0 34.1 Ministere de l’emploi, de la cohesion sociale et du lodement, DARES, Les expositions aux produits cancérogènes, Premières Synthèses Informations, No 28.1, Juillet 2005. Available at: http://www.eurofound.europa.eu/
  35. Ministere de l’emploi, de la cohesion sociale et du lodement, DARES, Les expositions aux produits cancérogènes en 2010, Premières Synthèses Informations, No 054, Septembre 2013. Available at: [29]
  36. EU-OSHA - European Agency for Safety and Health at Work (2013). FR - Quality of work - Results of the most recent SUMER survey. Retrieved 25 February 2014, from: [30]
  37. Saalo, A., Soosaar, A., Länsimäki, E. & Kauppinen, T., ASA 2005 (in Finnish), Finnish Institute of Occupational Health, Helsinki, 2007.
  38. 38.0 38.1 Carey, R.N., Driscoll, T.R., Peters, S., Glass, D.C., Reid, A., Benke, G. & Fritschi, L., 'Estimated prevalence of exposure to occupational carcinogens in Australia (2011–2012)', Occup Environ Med, 71, 2014, pp.55-62. Available at: [31]
  39. Takkala, J. & Schneider, E., Safety and health at work: Trends and main factors of occupational accidents and work-related illnesses, 2009.
  40. Takkouche, B., Regueira-Méndez, C. & Montes-Martínez, A., 'Risk of cancer among hairdressers and related workers: a meta-analysis', Int. J. Epidemiol., 38 (6), 2009, pp. 1512-1531. Available at: [32]
  41. ILO - International Labour Organization, C139 - Occupational Cancer Convention, 1974, Convention concerning Prevention and Control of Occupational Hazards caused by Carcinogenic Substances and Agents, Entry into force: 10 Jun 1976, Adoption: Geneva, 59th ILC session, 24 Jun 1974, Status: Up-to-date instrument, Technical Convention. Available at: [33]
  42. Directive 2004/37/EC - carcinogens or mutagens at work of 29 April 2004 on the protection of workers from the risks related to exposure to carcinogens or mutagens at work (Sixth individual Directive within the meaning of Article 16(1) Directive 89/391/EEC), OJ L 158, 30.4.2004. Available at: [34]
  43. ETUI – European Trade Union Institute (2012). Carcinogens Directive revision: major milestone passed. Retrieved 4 July 2013, from: [35]
  44. Pospischil, E., The concept of SCOEL concerning OEL's for carcinogens – Approach on OEL recommendations and examples, presentation at MEDICHEM Mini-Symposium on 'Occupational carcinogens: exposure scenarios and health risk', Vienna, 2011. Retrieved 1 April 2014, from: [36]
  45. European Commission, Methodology for the Derivation of Occupational Exposure Limits, Scientific Committee on Occupational Exposure Limits (SCOEL), Key Documentation, version 7, June, 2013. Available at: [37]
  46. Czerczak S., ‘Zasady ustalania wartości najwyższych dopuszczalnych stężeń chemicznych czynników szkodliwych w środowisku pracy’, Podstawy i Metody Oceny Środowiska Pracy, 4(42), 2004, pp. 5-18.
  47. Wriedt, H., The German exposure risk management model, Presentation at the EU-OSHA Workshop: Carcinogens and work-related cancer in Berlin, 2012. Retrieved 4 July 2013, from: [38]
  48. Bender, H.F., Acceptable, tolerable, non-tolerable risks at the workplace, Presentation at the EU-OSHA Workshop: Carcinogens and work-related cancer in Berlin, 2012. Retrieved 4 July 2013, from: [39]
  49. 49.0 49.1 EU-OSHA – European Agency for Safety and Health at Work, Exploratory survey of occupational exposure limits for carcinogens, mutagens and reprotoxic substances at EU Member State levels, Luxembourg, Office for Official Publications of the European Communities, 2009. Available at: [40]
  50. DG Employment, Social Affairs and Inclusion, Evaluation of the European Strategy on Safety and Health at Work 2007-2012, Final report prepared by milieu, IOM and COWI, 2013. Available at: [[41]
  51. Schenk, L. & Johanson, G., ‘A Quantitative Comparison of the Safety Margins in the European Indicative Occupational Exposure Limits and the Derived No-Effect Levels for Workers under REACH’, Toxicological Sciences, 2011, 121(2), pp. 408–416.
  52. ECHA – European Chemicals Agency, Guidance on information requirements and chemical safety assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health, version 2.1, Nov. 2012. Available at: [42]
  53. 53.0 53.1 European Commission, Report on the current situation in relation to occupational diseases’ systems in EU Member States and EFTA/EEA countries, in particular relative to Commission Recommendation 2003/670/EC concerning the European Schedule of Occupational Diseases and gathering of data on relevant related aspects, 2013. Available at: [43]
  54. ETUI – European Trade Union Institute (no date). Occupational diseases. Retrieved 3 October 2013, from: [44]
  55. ETUI – European Trade Union Institute (no date). Occupational diseases. Retrieved 3 October 2013, from: [45]
  56. Hien, W., 'Beruflich verursachte Krebserkrankungen: Neue Herausforderungen (Cancer caused by occupation: new challenges)', gute Arbeit, Frankfurt, 10, 2013, pp. 24-27. Available at: [46]
  57. Melzer, F., 'Nur jeder fünfte Antrag kommt durch (Only every fifth application is successful)', Metallzeitung, Frankfurt, 2, 2014.
  58. ETUI - European Trade Union Institute, Women and occupational diseases - The-case-of-Belgium, Brussels, 2011, pp.14-15. Available at: [47]
  59. Ahrens, A., Braun, A., von Gleich, A., Heitmann, K. & Lißner, L., Hazardous Chemicals in Products and Prozesses - Substitution and Beyond, Series: Innovation and Sustainability, Physica-Verlag, Heidelberg, Berlin, 2006.
  60. HVBG – Hauptverband der gewerblichen Berufsgenossenschaften, Manipulation von Schutzeinrichtungen an Maschinen (manipulation of safety devices at machines), 2006. Available at: [48]
  61. BAuA - Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (German federal agency for safety at work and occupational medicine) (2013), Technical Rules for Hazardous Substances (TRGS). Retrieved 28 October 2013, from: [49]
  62. European Commission, Occupational health and safety risks in the health care sector - Guide to prevention and good practice, Luxembourg, Publications Office of the European Union, 1-282, 2011. Avaiable at: [50]
  63. EU-OSHA - European Agency for Safety and Health at Work (no date). Case studies (Searchstring: 'Nano'). Retrieved 1 April 2014, from: [51]
  64. European Commission, Occupational health and safety risks in the health care sector - Guide to prevention and good practice, Luxembourg, Publications Office of the European Union, 1-282, 2011. Avaiable at: [52]
  65. NIOSH - National Institute for Occupational Safety and Health (USA), The Effect of Workplace Hazards on Female Reproductive Health, DHSS (NIOSH) Publication No. 99-104,1999, p.5. Available at: [53]
  66. BAuA - Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (German federal agency for safety at work and occupational medicine) Technical Rules for Biological Agents (TRBA). Retrieved 1 April 2014, from: [54]
  67. BAuA - Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (German federal agency for safety at work and occupational medicine), TRBA 500 Basic Measures to be taken for Activities involving Biological Agents, 2012. Available at: [55]
  68. EU-OSHA - European Agency for Safety and Health at Work, New risks and trends in the safety and health of women at work, European Risk Observatory, Literature review, Luxembourg: Publications Office of the European Union, 2013. Available at: [56]
  69. INCA - French National Cancer Institute, Cancer Pro Actu - Newsletter documentary on the prevention of occupational cancers (only in French) . Available at: [57]
  70. INCA - French National Cancer Institute, Cancers Doc Pro - Guide to resources on the primary prevention of occupational cancers (only in French) . Available at: [58]

Links for further reading

EU-OSHA – European Agency for Safety and Health at Work, Exposure to carcinogens and work-related cancer: a review of assessment methods, European Risk Observatory Report, Luxembourg: Publications Office of the European Union, 2014. Available at: [59]

EU-OSHA – European Agency for Safety and Health at Work, Summary - Exposure to carcinogens and work-related cancer - A review of assessment measures, summary of European Risk Observatory Report, Luxembourg: Publications Office of the European Union, 2014. Available at: [60]

FIOH – Finnish Institute of Occupational Health (21.06.2010). CAREX - International Information System on Occupational Exposure to Carcinogens. Retrieved on 21 August 2013, from: [61]

Driscoll, T., Nelson, D., Steenland, K., Leigh, J., Concha-Barrientos, M., Fingerhut, M., Prüss-Üstün, A., ‘The global burden of diseases due to occupational carcinogens’, Am J Indust Med 48, 2005, pp. 419-431. Available at: [62]

Karjalainen, A., Niederlander, E,. ‘Occupational diseases in Europe in 2001’, Statistics in focus 15/2004, European Communities, 2004.

Pukkala, E., Martinsen, J.I., Lynge, E., Gunnarsdottir, H.K., Sparén, P., Tryggvadottir, L., Weiderpass, E., Kjaerheim, K., ‘Occupation and cancer – follow-up of 15 million people in five Nordic countries’, Acta Oncol 48, 2009, pp. 646-790. Available at: [63], [64] and [65]

OSH: CancerCancer registerCarcinogensAsbestosDangerous substances managementIonising radiationShift workShift workersExposure routesEndocrine disruptorsDustsBiological hazardsDangerous substances
NACE: Crop and animal productionForestry and loggingAquacultureMINING AND QUARRYINGManufacture of food productsManufacture of beveragesManufacture of tobacco productsManufacture of textilesManufacture of wearing apparelManufacture of leather and related productsManufacture of wood and of products of wood and corkManufacture of paper and paper productsPrinting and reproduction of recorded mediaManufacture of coke and refined petroleum productsManufacture of chemicals and chemical productsManufacture of basic pharmaceutical products and pharmaceutical preparationsManufacture of rubber and plastic productsManufacture of other non-metallic mineral productsManufacture of basic metalsManufacture of fabricated metal productsManufacture of computerManufacture of electrical equipmentManufacture of machinery and equipment n.e.c.Manufacture of motor vehiclesManufacture of other transport equipmentRepair and installation of machinery and equipmentElectricitySewerageWaste collectionRemediation activities and other waste management servicesOFFICE CLERKSCivil engineeringSpecialised construction activitiesMaintenance and repair of motor vehiclesSaleHuman health activitiesResidential care activitiesHairdressing and other beauty treatmentWashing and (dry-