The control of occupational carcinogens is based on the critical review of scientific investigations both in humans and in experimental systems. There are several review programmes being undertaken in different countries aimed at controlling occupational exposures which could be carcinogenic to humans. The criteria used in different programmes are not entirely consistent, leading occasionally to differences in the control of agents in different countries. For example, 4,4-methylene-bis-2-chloroaniline (MOCA) was classified as an occupational carcinogen in Denmark in 1976 and in the Netherlands in 1988, but only in 1992 has a notation “suspected human carcinogen” been introduced by the American Conference of Governmental Industrial Hygienists in the United States.

The International Agency for Research on Cancer (IARC) has established, within the framework of its Monographs programme, a set of criteria to evaluate the evidence of the carcinogenicity of specific agents. The IARC Monographs programme represents one of the most comprehensive efforts to review systematically and consistently cancer data, is highly regarded in the scientific community and serves as the basis for the information in this article. It also has an important impact on national and international occupational cancer control activities. The evaluation scheme is given in table 1.

Table 1.  Evaluation of evidence of carcinogenicity in the IARC Monographs programme.

1. The evidence for the induction of cancer in humans, which obviously plays an important role in the identification of human carcinogens is considered. Three types of epidemiological studies contribute to an assessment of carcinogenicity in humans: cohort studies, case-control studies and correlation (or ecological) studies. Case reports of cancer in humans may also be reviewed. The evidence relevant to carcinogenicity from studies in humans is classified into one of the following categories:

• Sufficient evidence of carcinogenicity: A causal relationship has been established between exposure to the agent, mixture or exposure circumstance and human cancer. That is, a positive relationship has been observed between the exposure and cancer in studies in which chance, bias and confounding could be ruled out with reasonable confidence.
• Limited evidence of carcinogenicity: A positive association has been observed between exposure to the agent, mixture or exposure circumstance and cancer for which a causal interpretation is considered to be credible, but chance, bias or confounding could not be ruled out with reasonable confidence.
• Inadequate evidence of carcinogenicity: The available studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association, or no data on cancer in humans are available.
• Evidence suggesting lack of carcinogenicity: There are several adequate studies covering the full range of levels of exposure that human beings are known to encounter, which are mutually consistent in not showing a positive association between exposure to the agent and the studied cancer at any observed level of exposure.

2. Studies in which experimental animals (mainly rodents) are exposed chronically to potential carcinogens and examined for evidence of cancer are reviewed and the degree of evidence of carcinogenicity is then classified into categories similar to those used for human data.

3. Data on biological effects in humans and experimental animals that are of particular relevance are reviewed. These may include toxicological, kinetic and metabolic considerations and evidence of DNA binding, persistence of DNA lesions or genetic damage in exposed humans. Toxicological information, such as that on cytotoxicity and regeneration, receptor binding and hormonal and immunological effects, and data on structure-activity relationship are used when considered relevant to the possible mechanism of the carcinogenic action of the agent.

4. The body of evidence is considered as a whole, in order to reach an overall evaluation of the carcinogenicity to humans of an agent, mixture or circumstance of exposure (see table 2).

Agents, mixtures and exposure circumstances are evaluated within the IARC Monographs if there is evidence of human exposure and data on carcinogenicity (either in humans or in experimental animals) (for IARC classification groups, see table 2).

Table 2.  IARC Monograph programme classification groups.

The agent, mixture or exposure circumstance is described according to the wording of one of the following categories:

Known and Suspected Occupational Carcinogens

At present, there are 22 chemicals, groups of chemicals or mixtures for which exposures are mostly occupational, without considering pesticides and drugs, which are established human carcinogens (table 3). While some agents such as asbestos, benzene and heavy metals are currently widely used in many countries, other agents have mainly an historical interest (e.g., mustard gas and 2-naphthylamine).

Table 3. Chemicals, groups of chemicals or mixtures for which exposures are mostly occupational (excluding pesticides and drugs).
Group 1-Chemicals carcinogenic to humans¹

¹ Evaluated in the IARC Monographs, Volumes 1-63 (1972-1995) (excluding pesticides and drugs).
² CAS Registry Nos. appear between parentheses.
³ This evaluation applies to the group of chemicals as a whole and not necessarily to all individual chemicals within the group.

An additional 20 agents are classified as probably carcinogenic to humans (Group 2A); they are listed in table 4, and include exposures that are currently prevalent in many countries, such as crystalline silica, formaldehyde and 1,3-butadiene. A large number of agents are classified as possible human carcinogens (Group 2B, table 5) - for example, acetaldehyde, dichloromethane and inorganic lead compounds. For the majority of these chemicals the evidence of carcinogenicity comes from studies in experimental animals.

Table 4. Chemicals, groups of chemicals or mixtures for which exposures are mostly occupational (excluding pesticides and drugs).
Group 2A—Probably carcinogenic to humans¹

¹ Evaluated in the IARC Monographs, Volumes 1-63 (1972-1995) (excluding pesticides and drugs).
² CAS Registry Nos. appear between parentheses.

Table 5. Chemicals, groups of chemicals or mixtures for which exposures are mostly occupational (excluding pesticides and drugs).
Group 2B—Possibly carcinogenic to humans¹

¹ Evaluated in the IARC Monographs, Volumes 1-63 (1972-1995) (excluding pesticides and drugs).
² CAS Registry Nos. appear between parentheses.

Occupational exposures may also occur during the production and use of some pesticides and drugs. Table 6 presents an evaluation of the carcinogenicity of pesticides; two of them, captafol and ethylene dibromide, are classified as probable human carcinogens, while a total of 20 others, including DDT, atrazine and chlorophenols, are classified as possible human carcinogens.

Table 6. Pesticides evaluated in IARC Monographs, Volumes 1-63(1972-1995)

¹ CAS Registry Nos. appear between parentheses.

Several drugs are human carcinogens (table 9): they are mainly alkylating agents and hormones; 12 more drugs, including chloramphenicol, cisplatine and phenacetin, are classified as probable human carcinogens (Group 2A). Occupational exposure to these known or suspected carcinogens, used mainly in chemotherapy, can occur in pharmacies and during their administration by nursing staff.

Table 7. Drugs evaluated in IARC Monographs, Volumes 1-63 (1972-1995).

¹ CAS Registry Nos. appear between parentheses.
² Suspected target organs are given in parentheses.

Several environmental agents are known or suspected causes of cancer in humans and are listed in table 8; although exposure to such agents is not primarily occupational, there are groups of individuals exposed to them because of their work: examples are uranium miners exposed to radon decay products, hospital workers exposed to hepatitis B virus, food processors exposed to aflatoxins from contaminated foods, outdoor workers exposed to ultraviolet radiation or diesel engine exhaust, and bar staff or waiters exposed to environmental tobacco smoke.

The IARC Monograph programme has covered most of the known or suspected causes of cancer; there are, however, some important groups of agents that have not been evaluated by IARC—namely, ionizing radiation and electrical and magnetic fields.

Table 8. Environmental agents/exposures known or suspected to cause cancer in humans.¹

¹ Agents and exposures, as well as medicines, occurring mainly in the occupational setting are excluded.

² Suspected target organs are given in parentheses.

³ IARC Monograph evaluation reported wherever available (1: human carcinogen; 2A: probable human carcinogen; 2B: possible human carcinogen); otherwise E: established carcinogen; S: suspected carcinogen.

⁴ Human exposure to polycyclic aromatic hydrocarbons occurs in mixtures, such as engine emissions, combustion fumes and soots. Several mixtures and individual hydrocarbons have been evaluated by IARC.

Industries and Occupations

Current understanding of the relationship between occupational exposures and cancer is far from complete; in fact, only 22 individual agents are established occupational carcinogens (table 9), and for many more experimental carcinogens no definitive evidence is available based on exposed workers. In many cases, there is considerable evidence of increased risks associated with particular industries and occupations, although no specific agents can be identified as aetiological factors. Table 10 present lists of industries and occupations associated with excess carcinogenic risks, together with the relevant cancer sites and the known (or suspected) causative agent(s).

Table 9. Industries, occupations and exposures recognized as presenting a carcinogenic risk.

Table 10.  Industries, occupations and exposures reported to present a cancer excess but for which the assessment of the carcinogenic risk is not definitive.

¹ PAH, polycyclic aromatic hydrocarbon.

² MOCA, 4,4’-methylene-bis-2-chloroaniline.

³ PCBs, polychlorinated biphenyls.

Table 9 presents industries, occupations and exposures in which the presence of a carcinogenic risk is considered to be established, whereas Table 10 shows industrial processes, occupations and exposures for which an excess cancer risk has been reported but evidence is not considered to be definitive. Also included in table 10 are some occupations and industries already listed in table 9, for which there is inconclusive evidence of association with cancers other than those mentioned in table 9. For example, the asbestos production industry is included in table 9 in relation to lung cancer and pleural and peritoneal mesothelioma, whereas the same industry is included in table 10 in relation to gastrointestinal neoplasms. A number of industries and occupations listed intables 9 and 10 have also been evaluated under the IARC Monographs programme. For example, “occupational exposure to strong inorganic acid mist containing sulphuric acid” was classified in Group 1 (carcinogenic to humans).

Constructing and interpreting such lists of chemical or physical carcinogenic agents and associating them with specific occupations and industries is complicated by a number of factors: (1) information on industrial processes and exposures is frequently poor, not allowing a complete evaluation of the importance of specific carcinogenic exposures in different occupations or industries; (2) exposures to well-known carcinogenic exposures, such as vinyl chloride and benzene, occur 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 exposures can refer only to the relatively small number of chemical exposures which have been investigated with respect to the presence of a carcinogenic risk.

All of the above issues emphasize the most critical limitation of a classification of this type, and in particular its generalization to all areas of the world: the presence of a carcinogen in an occupational situation does not necessarily mean that workers are exposed to it and, in contrast, the absence of identified carcinogens does not exclude the presence of yet unidentified causes of cancer.

A particular problem in developing countries is that much of the industrial activity is fragmented and takes place in local settings. These small industries are often characterized by old machinery, unsafe buildings, employees with limited training and education, and employers with limited financial resources. Protective clothing, respirators, gloves and other safety equipment are seldom available or used. The small companies tend to be geographically scattered and inaccessible to inspections by health and safety enforcement agencies.

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