Kogevinas, Manolis

Kogevinas, Manolis

 

Address: Institut Municipal d'Investigació Mèdica (IMIM), Dr. Aiguader Rd. 80, 08003 Barcelona

Country: Spain

Phone: 34 3 221 1009

Fax: 34 3 221 3237

E-mail: kogevinas@imim.es

Past position(s): Epidemiologist, Unit of Analytical Epidemiology, International Agency for Research on Cancer

Education: Medical Degree, 1982, Medical School of Athens, Greece; MSc, 1984, London School of Hygiene and Tropical Medicine; PhD, 1989, University of London

Areas of interest: Occupational cancer; occupational respiratory diseases; health effects of dioxins and; other organochlorinated compounds

 

 

Tuesday, 25 January 2011 19:15

Occupational Carcinogens

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:

Group 1— The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
Group 2A— The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
Group 2B— The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
Group 3— The agent (mixture, exposure circumstance) is not classifiable as to its carcinogenicity to humans.
Group 4— The agent (mixture, exposure circumstance) is probably not carcinogenic to humans.

 

 

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

Exposure2 Human target organ(s) Main industry/use
4-Aminobiphenyl (92-67-1) Bladder Rubber manufacture
Arsenic (7440-38-2) and arsenic compounds3 Lung, skin Glass, metals, pesticides
Asbestos (1332-21-4) Lung, pleura, peritoneum Insulation, filter material, textiles
Benzene (71-43-2) Leukaemia Solvent, fuel
Benzidine (92-87-5) Bladder Dye/pigment manufacture, laboratory agent
Beryllium (7440-41-7) and beryllium compounds Lung Aerospace industry/metals
Bis(chloromethyl)ether (542-88-11) Lung Chemical intermediate/by-product
Chloromethyl methylether (107-30-2) (technical grade) Lung Chemical intermediate/by-product
Cadmium (7440-43-9) and cadmium compounds Lung Dye/pigment manufacture
Chromium (VI) compounds Nasal cavity, lung Metal plating, dye/pigment manufacture
Coal-tar pitches (65996-93-2) Skin, lung, bladder Building material, electrodes
Coal-tars (8007-45-2) Skin, lung Fuel
Ethylene oxide (75-21-8) Leukaemia Chemical intermediate, sterilant
Mineral oils, untreated and mildly treated Skin Lubricants
Mustard gas (sulphur mustard)
(505-60-2)
Pharynx, lung War gas
2-Naphthylamine (91-59-8) Bladder Dye/pigment manufacture
Nickel compounds Nasal cavity, lung Metallurgy, alloys, catalyst
Shale-oils (68308-34-9) Skin Lubricants, fuels
Soots Skin, lung Pigments
Talc containing asbestiform fibers Lung Paper, paints
Vinyl chloride (75-01-4) Liver, lung, blood vessels Plastics, monomer
Wood dust Nasal cavity Wood industry

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

Exposure2 Suspected human target organ(s) Main industry/use
Acrylonitrile (107-13-1) Lung, prostate, lymphoma Plastics, rubber, textiles, monomer
Benzidine-based dyes Paper, leather, textile dyes
1,3-Butadiene (106-99-0) Leukaemia, lymphoma Plastics, rubber, monomer
p-Chloro-o-toluidine (95-69-2) and its strong acid salts Bladder Dye/pigment manufacture, textiles
Creosotes (8001-58-9) Skin Wood preservation
Diethyl sulphate (64-67-5) Chemical intermediate
Dimethylcarbamoyl chloride (79-44-7) Chemical intermediate
Dimethyl sulphate (77-78-1) Chemical intermediate
Epichlorohydrin (106-89-8) Plastics/resins monomer
Ethylene dibromide (106-93-4) Chemical intermediate, fumigant, fuels
Formaldehyde (50-0-0) Nasopharynx Plastics, textiles, laboratory agent
4,4´-Methylene- bis-2-chloroaniline (MOCA)
(101-14-4)
Bladder Rubber manufacture
Polychlorinated biphenyls (1336-36-3) Liver, bile ducts, leukaemia, lymphoma Electrical components
Silica (14808-60-7), crystalline Lung Stone cutting, mining, glass, paper
Styrene oxide (96-09-3) Plastics, chemical intermediate
Tetrachloroethylene
(127-18-4)
Oesophagus, lymphoma Solvent, dry cleaning
Trichloroethylene (79-01-6) Liver, lymphoma Solvent, dry cleaning, metal
Tris(2,3-dibromopropylphosphate
(126-72-7)
Plastics, textiles, flame retardant
Vinyl bromide (593-60-2) Plastics, textiles, monomer
Vinyl fluoride (75-02-5) Chemical intermediate

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

Exposure2 Main industry/use
Acetaldehyde (75-07-0) Plastics manufacture, flavors
Acetamide (60-35-5) Solvent, chemical intermediate
Acrylamide (79-06-1) Plastics, grouting agent
p-Aminoazotoluene (60-09-3) Dye/pigment manufacture
o-Aminoazotoluene (97-56-3) Dyes/pigments, textiles
o-Anisidine (90-04-0) Dye/pigment manufacture
Antimony trioxide (1309-64-4) Flame retardant, glass, pigments
Auramine (492-80-8) (technical-grade) Dyes/pigments
Benzyl violet 4B (1694-09-3) Dyes/pigments
Bitumens (8052-42-4), extracts of
steam-refined and air-refined
Building material
Bromodichloromethane (75-27-4) Chemical intermediate
b-Butyrolactone (3068-88-0) Chemical intermediate
Carbon-black extracts Printing inks
Carbon tetrachloride (56-23-5) Solvent
Ceramic fibers Plastics, textiles, aerospace
Chlorendic acid (115-28-6) Flame retardant
Chlorinated paraffins of average carbon chain length C12 and average degree of chlorination approximately 60% Flame retardant
a-Chlorinated toluenes Dye/pigment manufacture, chemical intermediate
p-Chloroaniline (106-47-8) Dye/pigment manufacture
Chloroform (67-66-3) Solvent
4-Chloro-o-phenylenediamine (95-83-9) Dyes/pigments, hair dyes
CI Acid Red 114 (6459-94-5) Dyes/pigments, textiles, leather
CI Basic Red 9 (569-61-9) Dyes/pigments, inks
CI Direct Blue 15 (2429-74-5) Dyes/pigments, textiles, paper
Cobalt (7440-48-4)and cobalt compounds Glass, paints, alloys
p-Cresidine (120-71-8) Dye/pigment manufacture
N,N´-Diacetylbenzidine (613-35-4) Dye/pigment manufacture
2,4-Diaminoanisole (615-05-4) Dye/pigment manufacture, hair dyes
4,4´-Diaminodiphenyl ether (101-80-4) Plastics manufacture
2,4-Diaminotoluene (95-80-7) Dye/pigment manufacture, hair dyes
p-Dichlorobenzene (106-46-7) Chemical intermediate
3,3´-Dichlorobenzidine (91-94-1) Dye/pigment manufacture
3,3´-Dichloro-4,4´-diaminodiphenyl ether (28434-86-8) Not used
1,2-Dichloroethane (107-06-2) Solvent, fuels
Dichloromethane (75-09-2) Solvent
Diepoxybutane (1464-53-5) Plastics/resins
Diesel fuel, marine Fuel
Di(2-ethylhexyl)phthalate (117-81-7) Plastics, textiles
1,2-Diethylhydrazine (1615-80-1) Laboratory reagent
Diglycidyl resorcinol ether (101-90-6) Plastics/resins
Diisopropyl sulphate (29973-10-6) Contaminant
3,3´-Dimethoxybenzidine (o-Dianisidine)
(119-90-4)
Dye/pigment manufacture
p-Dimethylaminoazobenzene (60-11-7) Dyes/pigments
2,6-Dimethylaniline (2,6-Xylidine)(87-62-7) Chemical intermediate
3,3´-Dimethylbenzidine (o-Tolidine)(119-93-7) Dye/pigment manufacture
Dimethylformamide (68-12-2) Solvent
1,1-Dimethylhydrazine (57-14-7) Rocket fuel
1,2-Dimethylhydrazine (540-73-8) Research chemical
1,4-Dioxane (123-91-1) Solvent
Disperse Blue 1 (2475-45-8) Dyes/pigments, hair dyes
Ethyl acrylate (140-88-5) Plastics, adhesives, monomer
Ethylene thiourea (96-45-7) Rubber chemical
Fuel oils, residual (heavy) Fuel
Furan (110-00-9) Chemical intermediate
Gasoline Fuel
Glasswool Insulation
Glycidaldehyde (765-34-4) Textile, leather manufacture
HC Blue No. 1 (2784-94-3) Hair dyes
Hexamethylphosphoramide (680-31-9) Solvent, plastics
Hydrazine (302-01-2) Rocket fuel, chemical intermediate
Lead (7439-92-1) and lead compounds, inorganic Paints, fuels
2-Methylaziridine(75-55-8) Dyes, paper, plastics manufacture
4,4’-Methylene-bis-2-methylaniline (838-88-0) Dye/pigment manufacture
4,4’-Methylenedianiline(101-77-9) Plastics/resins, dye/pigment manufacture
Methylmercury compounds Pesticide manufacture
2-Methyl-1-nitroanthraquinone (129-15-7) (uncertain purity) Dye/pigment manufacture
Nickel, metallic (7440-02-0) Catalyst
Nitrilotriacetic acid (139-13-9) and its salts Chelating agent, detergent
5-Nitroacenaphthene (602-87-9) Dye/pigment manufacture
2-Nitropropane (79-46-9) Solvent
N-Nitrosodiethanolamine (1116-54-7) Cutting fluids, impurity
Oil Orange SS (2646-17-5) Dyes/pigments
Phenyl glycidyl ether (122-60-1) Plastics/adhesives/resins
Polybrominated biphenyls (Firemaster BP-6) (59536-65-1) Flame retardant
Ponceau MX (3761-53-3) Dyes/pigments, textiles
Ponceau 3R (3564-09-8) Dyes/pigments, textiles
1,3-Propane sulphone (1120-71-4) Dye/pigment manufacture
b-Propiolactone (57-57-8) Chemical intermediate; plastics manufacture
Propylene oxide (75-56-9) Chemical intermediate
Rockwool Insulation
Slagwool Insulation
Styrene (100-42-5) Plastics
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (1746-01-6) Contaminant
Thioacetamide (62-55-5) Textile, paper, leather, rubber manufacture
4,4’-Thiodianiline (139-65-1) Dye/pigment manufacture
Thiourea (62-56-6) Textile, rubber ingredient
Toluene diisocyanates (26471-62-5) Plastics
o-Toluidine (95-53-4) Dye/pigment manufacture
Trypan blue (72-57-1) Dyes/pigments
Vinyl acetate (108-05-4) Chemical intermediate
Welding fumes Metallurgy

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)

IARC Group Pesticide1
2A—Probably carcinogenic to humans Captafol (2425-06-1) Ethylene dibromide (106-93-4)
2B—Possibly carcinogenic to humans Amitrole (61-82-5) Atrazine (1912-24-9) Chlordane (57-74-9) Chlordecone (Kepone) (143-50-0) Chlorophenols Chlorophenoxy herbicides DDT (50-29-3) 1,2-Dibromo-3-chloropropane (96-12-8) 1,3-Dichloropropene (542-75-6) (technical-grade) Dichlorvos (62-73-7) Heptachlor (76-44-8) Hexachlorobenzene (118-74-1) Hexachlorocyclohexanes (HCH) Mirex (2385-85-5) Nitrofen (1836-75-5), technical-grade Pentachlorophenol (87-86-5) Sodium o-phenylphenate (132-27-4) Sulphallate (95-06-7) Toxaphene (Polychlorinated camphenes) (8001-35-2)

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).

Drug1 Target organ2
IARC GROUP 1—Carcinogenic to humans
Analgesic mixtures containing phenacetin Kidney, bladder
Azathioprine (446-86-6) Lymphoma, hepatobiliary system, skin
N,N-Bis(2-chloroethyl)- b-naphthylamine (Chlornaphazine) (494-03-1) Bladder
1,4-Butanediol dimethanesulphonate (Myleran)
(55-98-1)
Leukaemia
Chlorambucil (305-03-3) Leukaemia
1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Methyl-CCNU) (13909-09-6) Leukaemia
Cyclosporin (79217-60-0) Lymphoma, skin
Cyclophosphamide (50-18-0) (6055-19-2) Leukaemia, bladder
Diethylstilboestrol (56-53-1) Cervix, vagina, breast
Melphalan (148-82-3) Leukaemia
8-Methoxypsoralen (Methoxsalen) (298-81-7) plus ultraviolet A radiation Skin
MOPP and other combined chemotherapy including alkylating agents Leukaemia
Oestrogen replacement therapy Uterus
Oestrogens, nonsteroidal Cervix, vagina, breast
Oestrogens, steroidal Uterus
Oral contraceptives, combined Liver
Oral contraceptives, sequential Uterus
Thiotepa (52-24-4) Leukaemia
Treosulfan (299-75-2) Leukaemia

 

IARC GROUP 2A—Probably carcinogenic to humans
Adriamycin (23214-92-8)
Androgenic (anabolic) steroids (Liver)
Azacitidine (320-67-2)
Bischloroethyl nitrosourea (BCNU) (154-93-8) (Leukaemia)
Chloramphenicol (56-75-7) (Leukaemia)
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) (13010-47-4)
Chlorozotocine (54749-90-5)
Cisplatin (15663-27-1)
5-Methoxypsoralen (484-20-8)
Nitrogen mustard (51-75-2) (Skin)
Phenacetin (62-44-2) (Kidney, bladder)
Procarbazine hydrochloride (366-70-1)

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

Agent/exposure Target organ2 Strength of evidence3
Air pollutants
Erionite Lung, pleura 1
Asbestos Lung, pleura 1
Polycyclic aromatic hydrocarbons4 (Lung, bladder) S
Water pollutants
Arsenic Skin 1
Chlorination by-products (Bladder) S
Nitrate and nitrite (Oesophagus, stomach) S
Radiation
Radon and its decay products Lung 1
Radium, thorium Bone E
Other X-irradiation Leukaemia, breast, thyroid, others E
Solar radiation Skin 1
Ultraviolet radiation A (Skin) 2A
Ultraviolet radiation B (Skin) 2A
Ultraviolet radiation C (Skin) 2A
Use of sunlamps and sunbeds (Skin) 2A
Electric and magnetic fields (Leukaemia) S
Biological agents
Chronic infection with hepatitis B virus Liver 1
Chronic infection with hepatitis C virus Liver 1
Infection with Helicobacter pylori Stomach 1
Infection with Opistorchis viverrini Bile ducts 1
Infection with Chlonorchis sinensis (Liver) 2A
Human Papilloma virus types 16 and18 Cervix 1
Human Papilloma virus types 31 and 33 (Cervix) 2A
Human Papilloma virus types other than 16, 18, 31 and 33 (Cervix) 2B
Infection with Schistosoma haematobium Bladder 1
Infection with Schistosoma japonicum (Liver, colon) 2B
Tobacco, alcohol and related substances
Alcoholic beverages Mouth, pharynx, oesophagus, liver, larynx 1
Tobacco smoke Lip, mouth, pharynx, oesophagus, pancreas, larynx, lung, kidney, bladder, (others) 1
Smokeless tobacco products Mouth 1
Betel quid with tobacco Mouth 1
Dietary factors
Aflatoxins Liver 1
Aflatoxin M1 (Liver) 2B
Ochratoxin A (Kidney) 2B
Toxins derived from Fusarium moniliforme (Oesophagus) 2B
Chinese style salted fish Nasopharynx 1
Pickled vegetables (traditional in Asia) (Oesophagus, stomach) 2B
Bracken fern (Oesophagus) 2B
Safrole 2B
Coffee (Bladder) 2B
Caffeic acid 2B
Hot mate (Oesophagus) 2A
Fresh fruits and vegetables (protective) Mouth, oesophagus, stomach, colon, rectum, larynx, lung (others) E
Fat (Colon, breast, endometrium) S
Fiber (protective) (Colon, rectum) S
Nitrate and nitrite (Oesophagus, stomach) S
Salt (Stomach) S
Vitamin A, b-carotene (protective) (Mouth, oesophagus, lung, others) S
Vitamin C (protective) (Oesophagus, stomach) S
IQ (Stomach, colon, rectum) 2A
MeIQ 2B
MeIQx 2B
PhIP 2B
Reproductive and sexual behavior
Late age at first pregnancy Breast E
Low parity Breast, ovary, corpus uteri E
Early age at first intercourse Cervix E
Number of sexual partners Cervix E

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.

Industry (ISIC code) Occupation/process Cancer site/type Known or suspected causative agent
Agriculture, forestry and fishing (1) Vineyard workers using arsenic insecticides Fishermen Lung, skin Skin, lip Arsenic compounds Ultraviolet radiation
Mining and quarrying (2) Arsenic mining Iron ore (haematite) mining Asbestos mining Uranium mining Talc mining and milling Lung, skin Lung Lung, pleural and peritoneal mesothelioma Lung Lung Arsenic compounds Radon decay products Asbestos Radon decay products Talc containing asbestiform fibers
Chemical (35) Bis(chloromethyl) ether (BCME) and chloromethyl-methyl ether (CMME) production workers and users Vinyl chloride production Isopropyl alcohol manufacture (strong-acid process) Pigment chromate production Dye manufacturers and users Auramine manufacture p-chloro-o-toluidine production Lung (oat-cell carcinoma) Liver angiosarcoma Sinonasal Lung, sinonasal Bladder Bladder Bladder BCME, CMME Vinyl chloride monomer Not identified Chromium (VI) compounds Benzidine, 2-naphthylamine, 4-aminobiphenyl Auramine and other aromatic amines used in the process p-chloro-o-toluidine and its strong acid salts
Leather (324) Boot and shoe manufacture Sinonasal, leukaemia Leather dust, benzene
Wood and wood products (33) Furniture and cabinet makers Sinonasal Wood dust
Pesticides and herbicides production (3512) Arsenical insecticides production and packaging Lung Arsenic compounds
Rubber industry (355) Rubber manufacture Calendering, tyre curing, tyre building Millers, mixers Synthetic latex production, tyre curing, calender operatives, reclaim, cable makers Rubber film production Leukaemia Bladder Leukaemia Bladder Bladder Leukaemia Benzene Aromatic amines Benzene Aromatic amines Aromatic amines Benzene
Asbestos production (3699) Insulated material production (pipes, sheeting, textile, clothes, masks, asbestos cement products) Lung, pleural and peritoneal mesothelioma Asbestos
Metals (37) Aluminum production Copper smelting Chromate production, chromium plating Iron and steel founding Nickel refining Pickling operations Cadmium production and refining; nickel-cadmium battery manufacture; cadmium pigment manufacture; cadmium alloy production; electroplating; zinc smelters; brazing and polyvinyl chloride compounding Beryllium refining and machining; production of beryllium-containing products Lung, bladder Lung Lung, sinonasal Lung Sinonasal, lung Larynx, lung Lung Lung Polycyclic aromatic hydrocarbons, tar Arsenic compounds Chromium (VI) compounds Not identified Nickel compounds Inorganic acid mists containing sulphuric acid Cadmium and cadmium compounds Beryllium and beryllium compounds
Shipbuilding, motor vehicle and railroad equipment manufacture (385) Shipyard and dockyard, motor vehicle and railroad manufacture workers Lung, pleural and peritoneal mesothelioma Asbestos
Gas (4) Coke plant workers Gas workers Gas-retort house workers Lung Lung, bladder, scrotum Bladder Benzo(a)pyrene Coal carbonization products, 2-naphthylamine Aromatic amines
Construction (5) Insulators and pipe coverers Roofers, asphalt workers Lung, pleural and peritoneal mesothelioma Lung Asbestos Polycyclic aromatic hydrocarbons
Other Medical personnel (9331) Painters (construction, automotive industry and other users) Skin, leukaemia Lung Ionizing radiation Not identified


 

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

Industry (ISIC code) Occupation/process Cancer site/type Known (or suspected) causative agent
Agriculture, forestry and fishing (1) Farmers, farm workers Herbicide application Insecticide application Lymphatic and haematopoietic system (leukaemia, lymphoma) Malignant lymphomas, soft-tissue sarcomas Lung, lymphoma Not identified Chlorophenoxy herbicides, chlorophenols (presumably contaminated with polychlorinated dibenzodioxins) Non-arsenical insecticides
Mining and quarrying (2) Zinc-lead mining Coal Metal mining Asbestos mining Lung Stomach Lung Gastrointestinal tract Radon decay products Coal dust Crystalline silica Asbestos
Food industry (3111) Butchers and meat workers Lung Viruses, PAH1
Beverage industry (3131) Beer brewers Upper aero-digestive tract Alcohol consumption
Textile manufacture (321) Dyers Weavers Bladder Bladder, sinonasal, mouth Dyes Dusts from fibers and yarns
Leather (323) Tanners and processors Boot and shoe manufacture and repair Bladder, pancreas, lung Sinonasal, stomach, bladder Leather dust, other chemicals, chromium Not identified
Wood and wood products (33), pulp and paper industry (341) Lumbermen and sawmill workers Pulp and papermill workers Carpenters, joiners Woodworkers, unspecified Plywood production, particle-board production Nasal cavity, Hodgkin lymphoma, skin Lymphopoietic tissue, lung Nasal cavity, Hodgkin lymphoma Lymphomas Nasopharynx, sinonasal Wood dust, chlorophenols, creosotes Not identified Wood dust, solvents Not identified Formaldehyde
Printing (342) Rotogravure workers, binders, printing pressmen, machine-room workers and other jobs Lymphocytic and haemopoietic system, oral, lung, kidney Oil mist, solvents
Chemical (35) 1,3-Butadiene production Acrylonitrile production Vinylidene chloride production Isopropyl alcohol manufacture (strong-acid process) Polychloroprene production Dimethylsulphate production Epichlorohydrin production Ethylene oxide production Ethylene dibromide production Formaldehyde production Flame retardant and plasticizer use Benzoyl chloride production Lymphocytic and haemopoietic system Lung, colon Lung Larynx Lung Lung Lung, lymphatic and haemopoietic system (leukaemia) Lymphatic and haemopoietic system (leukaemia), stomach Digestive system Nasopharynx, sinonasal Skin (melanoma) Lung 1,3-Butadiene Acrylonitrile Vinylidene chloride (mixed exposure with acrylonitrile) Not identified Chloroprene Dimethylsulphate Epichlorohydrin Ethylene oxide Ethylene dibromide Formaldehyde Polychlorinated biphenyls Benzoyl chloride
Herbicides production (3512) Chlorophenoxy herbicide production Soft-tissue sarcoma Chlorophenoxy herbicides, chlorophenols (contaminated with polychlorinated dibenzodioxins)
Petroleum (353) Petroleum refining Skin, leukaemia, brain Benzene, PAH, untreated and mildly treated mineral oils
Rubber (355) Various occupations in rubber manufacture Styrene-butadiene rubber production Lymphoma, multiple myeloma, stomach, brain, lung Lymphatic and haematopoietic system Benzene, MOCA,2 other not identified 1,3-Butadiene
Ceramic, glass and refractory brick (36) Ceramic and pottery workers Glass workers (art glass, container and pressed ware) Lung Lung Crystalline silica Arsenic and other metal oxides, silica, PAH
Asbestos production (3699) Insulation material production (pipes, sheeting, textiles, clothes, masks, asbestos cement products) Larynx, gastrointestinal tract Asbestos
Metals (37, 38) Lead smelting Cadmium production and refining; nickel-cadmium battery manufacture; cadmium pigment manufacture; cadmium alloy production; electroplating; zinc smelting; brazing and polyvinyl chloride compounding Iron and steel founding Respiratory and digestive systems Prostate Lung Lead compounds Cadmium and cadmium compounds Crystalline silica
Shipbuilding (384) Shipyard and dockyard workers Larynx, digestive system Asbestos
Motor vehicle manufacturing (3843, 9513) Mechanics, welders, etc. Lung PAH, welding fumes, engine exhaust
Electricity (4101, 9512) Generation, production, distribution, repair Leukaemia, brain tumors Liver, bile ducts Extremely low frequency magnetic fields PCBs3
Construction (5) Insulators and pipe coverers Roofers, asphalt workers Larynx, gastrointestinal tract Mouth, pharynx, larynx, oesophagus, stomach Asbestos PAH, coal tar, pitch
Transport (7) Railroad workers, filling station attendants, bus and truck drivers, operators of excavating machines Lung, bladder Leukaemia Diesel engine exhaust Extremely low frequency magnetic fields
Other Service station attendants (6200) Chemists and other laboratory workers (9331) Embalmers, medical personnel (9331) Health workers (9331) Laundry and dry cleaners (9520) Hairdressers (9591) Radium dial workers Leukaemia and lymphoma Leukaemia and lymphoma, pancreas Sinonasal, nasopharynx Liver Lung, oesophagus, bladder Bladder, leukaemia and lymphoma Breast Benzene Not identified (viruses, chemicals) Formaldehyde Hepatitis B virus Tri- and tetrachloroethylene and carbon tetrachloride Hair dyes, aromatic amines Radon

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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Tuesday, 25 January 2011 19:12

Introduction

Magnitude of the Problem

The first clear-cut evidence of cancer causation involved an occupational carcinogen (Checkoway, Pearce and Crawford-Brown 1989). Pott (1775) identified soot as the cause of scrotal cancer in London chimney-sweeps, and graphically described the abysmal working conditions, which involved children climbing up narrow chimneys that were still hot. Despite this evidence, reports of the need to prevent fires in chimneys were used to delay legislation on child labour in this industry until 1840 (Waldron 1983). An experimental model of soot carcinogenesis was first demonstrated in the 1920s (Decoufle 1982), 150 years after the original epidemiological observation.

In subsequent years, a number of other occupational causes of cancer have been demonstrated through epidemiological studies (although the association with cancer has usually first been noted by occupational physicians or by workers). These include arsenic, asbestos, benzene, cadmium, chromium, nickel and vinyl chloride. Such occupational carcinogens are very important in public health terms because of the potential for prevention through regulation and improvements in industrial hygiene practices (Pearce and Matos 1994). In most instances, these are hazards which markedly increase the relative risk of a particular type or types of cancer. It is possible that other occupational carcinogens remain undetected because they involve only a small increase in risk or because they simply have not been studied (Doll and Peto 1981). Some key facts about occupational cancer are given in table 1.

 


Table 1. Occupational cancer: Key facts.

 

  • Some 20 agents and mixtures are established occupational carcinogens; a similar number of chemicals are highly suspected occupational carcinogens.
  • In industrialized countries, occupation is causally linked to 2 to 8% of all cancers; among exposed workers, however, this proportion is higher.
  • No reliable estimates are available on either the burden of occupational cancer or the extent of workplace exposure to carcinogens in developing countries.
  • The relatively low overall burden of occupational cancer in industrialized countries is the result of strict regulations on several known carcinogens; exposure to other known or highly suspected agents, however, is still allowed.
  • Although several occupational cancers are listed as occupational diseases in many countries, a very small fraction of cases is actually recognized and compensated.
  • Occupational cancer is-to a very large extent-a preventable disease.

 


 

Occupational causes of cancer have received considerable emphasis in epidemiological studies in the past. However, there has been much controversy regarding the proportion of cancers which are attributable to occupational exposures, with estimates ranging from 4 to 40% (Higginson 1969; Higginson and Muir 1976; Wynder and Gori 1977; Higginson and Muir 1979; Doll and Peto 1981; Hogan and Hoel 1981; Vineis and Simonato 1991; Aitio and Kauppinen 1991). The attributable cancer risk is the total cancer experience in a population that would not have occurred if the effects associated with the occupational exposures of concern were absent. It may be estimated for the exposed population, as well as for a broader population. A summary of existing estimates is shown in table 2. Universal application of the International Classification of Diseases is what makes such tabulations possible (see box).

Table 2.  Estimated proportions of cancer (PAR) attributable to occupations in selected studies.

Study Population PAR and cancer site Comments
Higginson 1969 Not stated 1% Oral cancer
1-2% Lung cancer
10% Bladder cancer
2% Skin cancer
No detailed presentation of exposure levels and other assumptions
Higginson and Muir 1976 Not stated 1-3% Total cancer No detailed presentation of assumptions
Wynder and Gori 1977 Not stated 4% Total cancer in men,
2% for women
Based on one PAR for bladder cancer and two personal communications
Higginson and Muir 1979 West Midland, United Kingdom 6% Total cancer in men,
2% total cancer
Based on 10% of non-tobacco related lung cancer, mesothelioma, bladder cancer (30%), and leukaemia in women (30%)
Doll and Peto 1981 United States early 1980 4% (range 2-8%)
Total cancer
Based on all studied cancer sites; reported as ‘tentative’ estimate
Hogan and Hoel 1981 United States 3% (range 1.4-4%)
Total cancer
Risk associated with occupational asbestos exposure
Vineis and Simonato 1991 Various 1-5% Lung cancer,
16-24% bladder cancer
Calculations on the basis of data from case-control studies. Percentage for lung cancer considers only exposure to asbestos. In a study with a high proportion of subjects exposed to ionising radiation, a 40% PAR was estimated. Estimates of PAR in a few studies on bladder cancer were between 0 and 3%.

 


The International Classification of Diseases

Human diseases are classified according to the International Classification of Diseases (ICD), a system that was started in 1893 and is regularly updated under the coordination of the World Health Organization. The ICD is used in almost all countries for tasks such as death certification, cancer registration and hospital discharge diagnosis. The Tenth Revision (ICD-10), which was approved in 1989 (World Health Organization 1992), differs considerably from the previous three revisions, which are similar to each other and have been in use since the 1950s. It is therefore likely that the Ninth Revision (ICD-9, World Health Organization 1978), or even earlier revisions, will still be used in many countries during the coming years.


The large variability in the estimates arises from the differences in the data sets used and the assumptions applied. Most of the published estimates on the fraction of cancers attributed to occupational risk factors are based on rather simplified assumptions. Furthermore, although cancer is relatively less common in developing countries due to the younger age structure (Pisani and Parkin 1994), the proportion of cancers due to occupation may be higher in developing countries due to the relatively high exposures which are encountered (Kogevinas, Boffetta and Pearce 1994).

The most generally accepted estimates of cancers attributable to occupations are those presented in a detailed review on the causes of cancer in the population of the United States in 1980 (Doll and Peto 1981). Doll and Peto concluded that about 4% of all the deaths due to cancer may be caused by occupational carcinogens within “acceptable limits” (i.e., still plausible in view of all the evidence at hand) of 2 and 8%. These estimates being proportions, they are dependent on how causes other than occupational exposures contribute to produce cancers. For example, the proportion would be higher in a population of lifetime non-smokers (such as the Seventh-Day Adventists) and lower in a population in which, say, 90% are smokers. Also the estimates do not apply uniformly to both sexes or to different social classes. Furthermore, if one considers not the whole population (to which the estimates refer), but the segments of the adult population in which exposure to occupational carcinogens almost exclusively occurs (manual workers in mining, agriculture and industry, broadly taken, who in the United States numbered 31 million out of a population, aged 20 and over, of 158 million in the late 1980s), the proportion of 4% in the overall population would increase to about 20% among those exposed.

Vineis and Simonato (1991) provided estimates on the number of cases of lung and bladder cancer attributable to occupation. Their estimates were derived from a detailed review of case-control studies, and demonstrate that in specific populations located in industrial areas, the proportion of lung cancer or bladder cancer from occupational exposures may be as high as 40% (these estimates being dependent not only on the local prevailing exposures, but also to some extent on the method of defining and assessing exposure).

Mechanisms and Theories of Carcinogenesis

Studies of occupational cancer are complicated because there are no “complete” carcinogens; that is, occupational exposures increase the risk of developing cancer, but this future development of cancer is by no means certain. Furthermore, it may take 20 to 30 years (and at least five years) between an occupational exposure and the subsequent induction of cancer; it may also take several more years for cancer to become clinically detectable and for death to occur (Moolgavkar et al. 1993). This situation, which also applies to non-occupational carcinogens, is consistent with current theories of cancer causation.

Several mathematical models of cancer causation have been proposed (e.g., Armitage and Doll 1961), but the model which is simplest and most consistent with current biological knowledge is that of Moolgavkar (1978). This assumes that a healthy stem cell occasionally mutates (initiation); if a particular exposure encourages the proliferation of intermediate cells (promotion) then it becomes more likely that at least one cell will undergo one or more further mutations producing a malignant cancer (progression) (Ennever 1993).

Thus, occupational exposures can increase the risk of developing cancer either by causing mutations in DNA or by various “epigenetic” mechanisms of promotion (those not involving damage to DNA), including increased cell proliferation. Most occupational carcinogens which have been discovered to date are mutagens, and therefore appear to be cancer initiators. This explains the long “latency” period which is required for further mutations to occur; in many instances the necessary further mutations may never occur, and cancer may never develop.

In recent years, there has been increasing interest in occupational exposures (e.g., benzene, arsenic, phenoxy herbicides) which do not appear to be mutagens, but which may act as promoters. Promotion may occur relatively late in the carcinogenic process, and the latency period for promoters may therefore be shorter than for initiators. However, the epidemiological evidence for cancer promotion remains very limited at this time (Frumkin and Levy 1988).

Transfer of Hazards

A major concern in recent decades has been the problem of the transfer of hazardous industries to the developing world (Jeyaratnam 1994). Such transfers have occurred in part due to the stringent regulation of carcinogens and increasing labour costs in the industrialized world, and in part from low wages, unemployment and the push for industrialization in the developing world. For example, Canada now exports about half of its asbestos to the developing world, and a number of asbestos-based industries have been transferred to developing countries such as Brazil, India, Pakistan, Indonesia and South Korea (Jeyaratnam 1994). These problems are further compounded by the magnitude of the informal sector, the large numbers of workers who have little support from unions and other worker organizations, the insecure status of workers, the lack of legislative protection and/or the poor enforcement of such protection, the decreasing national control over resources, and the impact of the third world debt and associated structural adjustment programmes (Pearce et al. 1994).

As a result, it cannot be said that the problem of occupational cancer has been reduced in recent years, since in many instances the exposure has simply been transferred from the industrialized to the developing world. In some instances, the total occupational exposure has increased. Nevertheless, the recent history of occupational cancer prevention in industrialized countries has shown that it is possible to use substitutes for carcinogenic compounds in industrial processes without leading industry to ruin, and similar successes would be possible in developing countries if adequate regulation and control of occupational carcinogens were in place.

Prevention of Occupational Cancer

Swerdlow (1990) outlined a series of options for the prevention of exposure to occupational causes of cancer. The most successful form of prevention is to avoid the use of recognized human carcinogens in the workplace. This has rarely been an option in industrialized countries, since most occupational carcinogens have been identified by epidemiological studies of populations that were already occupationally exposed. However, at least in theory, developing countries could learn from the experience of industrialized countries and prevent the introduction of chemicals and production processes that have been found to be hazardous to the health of workers.

The next best option for avoiding exposure to established carcinogens is their removal once their carcinogenicity has been established or suspected. Examples include the closure of plants making the bladder carcinogens 2-naphthylamine and benzidine in the United Kingdom (Anon 1965), termination of British gas manufacture involving coal carbonization, closure of Japanese and British mustard gas factories after the end of the Second World War (Swerdlow 1990) and gradual elimination of the use of benzene in the shoe industry in Istanbul (Aksoy 1985).

In many instances, however, complete removal of a carcinogen (without closing down the industry) is either not possible (because alternative agents are not available) or is judged politically or economically unacceptable. Exposure levels must therefore be reduced by changing production processes and through industrial hygiene practices. For example, exposures to recognized carcinogens such as asbestos, nickel, arsenic, benzene, pesticides and ionizing radiation have been progressively reduced in industrialized countries in recent years (Pearce and Matos 1994).

A related approach is to reduce or eliminate the activities that involve the heaviest exposures. For example, after an 1840 act was passed in England and Wales prohibiting chimney-sweeps from being sent up chimneys, the number of cases of scrotal cancer decreased (Waldron 1983). Exposure also can be minimized through the use of protective equipment, such as masks and protective clothing, or by imposing more stringent industrial hygiene measures.

An effective overall strategy in the control and prevention of exposure to occupational carcinogens generally involves a combination of approaches. One successful example is a Finnish registry which has as its objectives to increase awareness about carcinogens, to evaluate exposure at individual workplaces and to stimulate preventive measures (Kerva and Partanen 1981). It contains information on both workplaces and exposed workers, and all employers are required to maintain and update their files and to supply information to the registry. The system appears to have been at least partially successful in decreasing carcinogenic exposures in the workplace (Ahlo, Kauppinen and Sundquist 1988).

 

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Contents

Preface
Part I. The Body
Part II. Health Care
Part III. Management & Policy
Part IV. Tools and Approaches
Part V. Psychosocial and Organizational Factors
Part VI. General Hazards
Part VII. The Environment
Part VIII. Accidents and Safety Management
Part IX. Chemicals
Part X. Industries Based on Biological Resources
Part XI. Industries Based on Natural Resources
Part XII. Chemical Industries
Part XIII. Manufacturing Industries
Part XIV. Textile and Apparel Industries
Part XV. Transport Industries
Part XVI. Construction
Part XVII. Services and Trade
Part XVIII. Guides