Listing occupational carcinogens.

The occupational environment has been a most fruitful one for investigating the etiology of human cancer. Many recognized human carcinogens are occupational carcinogens. There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various organizations and individuals have published lists of occupational carcinogens. However, such lists have been limited by unclear criteria for which recognized carcinogens should be considered occupational carcinogens, and by inconsistent and incomplete information on the occupations and industries in which the carcinogenic substances may be found and on their target sites of cancer. Based largely on the evaluations published by the International Agency for Research on Cancer, and augmented with additional information, the present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs. We have considered 28 agents as definite occupational carcinogens, 27 agents as probable occupational carcinogens, and 113 agents as possible occupational carcinogens. These tables should be useful for regulatory or preventive purposes and for scientific purposes in research priority setting and in understanding carcinogenesis. Key words: cancer, environment, epidemiology, occupation, review. Environ Health Perspect 112:1447-1459 (2004). doi:10.1289/ehp.7047 available via http://dx.doi.org/ [Online 15 July 2004]

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Occupational carcinogens occupy a special place among the different classes of human carcinogens. The occupational environment has been a most fruitful one for investigating the etiology and pathogenesis of human cancer. Up to the 1970s, most recognized human carcinogens were substances or circumstances found primarily in the occupational environment, and although this may no longer be true with the growing list of recognized non-occupational carcinogens, they still represent a large fraction of the total. Although it is important to discover occupational carcinogens for the sake of preventing occupational cancer, the potential benefit of such discoveries goes beyond the factory walls because most occupational exposures find their way into the general environment, sometimes at higher concentrations than in the workplace.

There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various national and international bodies have published lists of carcinogens, but available lists of occupational carcinogens have been limited in various ways. Among the issues that are often missing, or treated rather casually, are a coherent assessment of which substances should be considered occupational carcinogens; information on the occupations and industries in which the carcinogenic substances may be found; and the target sites of cancer. The present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs.

Methods and Results

Difficulties in listing occupational carcinogens. Although it seems like a simple enough task, it is very difficult to draw up an unambiguous list of occupational carcinogens. The first source of ambiguity concerns the definition of an "occupational" carcinogen. Most occupational exposures are also found in the general environment, and/or in consumer products; most general environmental exposures and consumer products, including medications, foods, and others, are found in some occupational environments. The distinctions can be quite arbitrary. For instance, although tobacco smoke, sunlight, and immunosuppressive medications are not primarily considered to be occupational exposures, there certainly are workers whose occupations bring them into contact with these agents. Also, although asbestos, benzene, and radon gas are considered to be occupational carcinogens, they are also found widely among the general population, and indeed, it is likely that many more people are exposed to these substances outside than inside the occupational environment. There is no simple rule to earmark occupational carcinogens as opposed to nonoccupational ones. Further, some carcinogens are chemicals that are used for research purposes and to which few people would ever be exposed, whether occupationally or nonoccupationally. Our operational criterion for designating occupational carcinogens is outlined below.

A second source of ambiguity derives from the rather idiosyncratic nature of the evidence. In some instances, we know that an occupational or industrial group is at excess risk of cancer, and we have a good idea of the causative agent; for example, scrotal cancer among chimney sweeps and polyaromatic hydrocarbons (PAHs) in soot (Waldron 1983), and lung cancer among asbestos miners and asbestos fibers [International Agency for Research on Cancer (IARC) 1977]. In some instances, we know that a group experienced excess risk but the causative agent is unknown or at least unproven [e.g., lung cancer among painters (IARC 1989c), bladder cancer among workers in the aluminum industry (IARC 1987)]. The strength of the evidence for an association can vary. For some associations, the evidence of excess risk seems incontrovertible [e.g., liver angiosarcoma and vinyl chloride monomer (IARC 1979b), bladder cancer and benzidine (IARC 1982b)]. For some associations, the evidence is suggestive [e.g., lung cancer and diesel engine exhaust (IARC 1989a), bladder cancer and employment as a painter (IARC 1989c)]. Among the many substances in the industrial environment for which there are no human data concerning carcinogenicity, there are hundreds that have been shown to be carcinogenic in some animal species and thousands that have been shown to have some effect in assays of mutagenicity or genotoxicity. These considerations complicate the attempt to devise a list of occupational carcinogens.

IARC Monographs. For this task we drew on the authoritative IARC Monograph Program and its evaluation of carcinogenic risks to humans (IARC 1987). The objective of the IARC Monograph Program, which has been operating since 1971, is to publish critical reviews of epidemiologic and experimental data on carcinogenicity for chemicals, groups of chemicals, industrial processes, other complex mixtures, physical agents, and biologic agents to which humans are known to be exposed, to evaluate the data in terms of human risk, and to indicate where additional research efforts are needed.

Substances are selected by IARC for evaluation on the basis of two main criteria: a) humans are exposed, and b) there is reason to suspect that the substance may be carcinogenic. Direct evidence concerning carcinogenicity of a substance can come from epidemiologic studies among humans or from experimental studies of animals (usually rodents). Additional evidence comes from the results of studies of chemical structure-activity analysis, absorption and metabolism, physiology, mutagenicity, cytotoxicology, and other aspects of toxicity. In the IARC Monographs, all types of data contribute to the evaluation.

In this article, we outline the IARC process because it is important to understand how decisions are made in order to properly interpret these decisions. IARC evaluations are carried out during specially convened meetings that typically last a week. The meetings may evaluate only one agent, such as silica, or they may address a set of related agents or even exposure circumstances such as an occupation or an industry. For each such meeting, and there have typically been three per year, IARC convenes an international working group, usually involving from 15 to 30 experts on the topic(s) being evaluated, from four perspectives, a) exposure and occurrence of the substances being evaluated, b) human evidence of cancer risk (i.e., epidemiology), c) animal carcinogenesis, and d) other data relevant to the evaluation of carcinogenicity and its mechanisms. The working group is asked to review all of the literature relevant to an assessment of carcinogenicity. In the first part of the meeting, four subgroups (based on the four perspectives mentioned above) review and revise drafts prepared by members of the subgroup, and each subgroup develops a joint review and evaluation of the evidence on which they have focused. Subsequently, the entire working group convenes in plenary and proceeds to derive a joint text. They determine whether the epidemiologic evidence supports the hypothesis that the substance causes cancer, and, separately, whether the animal evidence supports the hypothesis that the substance causes cancer. The judgments are not simply dichotomous (yes/no), but rather they allow the working group to express a range of opinions on each of the dimensions evaluated. Table 1 shows the categories into which the working groups are asked to classify each substance, when examining only the epidemiologic evidence and when examining only the animal experimental evidence. The operational criteria for making these decisions leave room for interpretation, and the scientific evidence itself is open to interpretation. It is not surprising, then, that the evaluations are sometimes difficult and contentious.

The overall evaluation of human carcinogenicity is based on the epidemiologic and animal evidence of carcinogenicity, plus any other relevant evidence on genotoxicity, mutagenicity, metabolism, or mechanisms. Epidemiologic evidence, where it exists, is given greatest weight. Direct animal evidence of carcinogenicity is next in importance, with increasing attention paid to mechanistic evidence that can inform the relevance of the animal evidence for human risk assessment.

Table 2 shows the categories for the overall evaluation and how they are derived from human, animal, and other evidence. Each substance is classified into one of the following groups: carcinogenic (group 1), probably carcinogenic (group 2A), possibly carcinogenic (group 2B), not classifiable (group 3), probably not carcinogenic (group 4). However, the algorithm implied by Table 2 is only indicative, and the working group may derive an overall evaluation that departs from the strict interpretation of the algorithm. For example, neutrons have been classified as human carcinogens (group 1) despite the absence of epidemiologic data, because of overwhelming experimental evidence and mechanistic considerations (IARC 2000a). The IARC process relies on consensus, and this is usually achieved, but sometimes differing opinions among experts lead to split decisions. In the end, the published evaluations reflect the views of at least a majority of participating experts. The results of IARC evaluations are published in readily available and user-friendly volumes, and summaries are published on the IARC website (IARC 2003).

For our purpose, there are several limitations to bear in mind. First, IARC does not provide any explicit indication as to whether the substance evaluated should be considered an occupational exposure. Second, although the working groups certainly study the evidence in relation to cancer sites, until recently the formal evaluations did not identify which sites of cancer may be at risk. Site-specific information needs to be gleaned from the working group's report and other literature. Third, the evaluations are anchored in the time that the working group met and reviewed the evidence; it is possible that evidence appearing after the IARC review could change the evaluation.

Current knowledge on occupational carcinogens. From 1972 through 2003, the IARC Monograph Program published 83 volumes, representing evaluations of more than 880 substances, complex mixtures, and industrial processes. Of these, 89 have been classed as definite human carcinogens, 64 as probable, and 264 as possible human carcinogens (IARC 2003). We reviewed each one and earmarked those that we consider to be "occupational exposures."

In developing a decision rule, we considered the following dimensions: whether the evidence of an effect drew on studies in exposed workers, whether the agent was found more often in the occupational or nonoccupational environments, and the numbers of workers exposed. In the end, the first two dimensions became redundant when we applied the third. Thus, a substance was considered an occupational exposure if there are, or have been, significant numbers of workers exposed to the substance at significant levels. The fact that some workers were exposed to a substance was not enough to label it as an occupational carcinogen. There are many carcinogens to which few workers are exposed, and we did not want to dilute the lists with such obscure agents.

Unfortunately, the knowledge base for determining how many workers are or have been exposed, and at what levels, is very fragmentary. We relied on available documentation such as the IARC Monographs, surveys by the National Institute for Occupational Safety and Health (NIOSH 1990), the National Toxicology Program (NTP) Report on Carcinogens, Tenth Edition (NTP 2002), and informed guesses on the part of expert industrial hygienists. Where we could come up with approximate numbers of workers exposed, we had to have some type of operational threshold for what should be considered a significant number. As a rule of thumb, we used > 10,000 workers exposed worldwide or > 1,000 in any country, presently or at any time in the past. These were the guidelines against which we measured our imprecise and semisubjective estimates. We also had to operationalize the notion of a level of exposure that was significant. This was even less explicit than the criteria used for numbers of workers exposed; it depended, inter alia, on the known range of exposure levels to the agent.

Despite the fact that they may be found in occupational environments, some classes of agents were summarily excluded from consideration on the grounds that the exposures are rare or very infrequent or at very low doses. These included hormones, pharmaceuticals, microbiologic agents, and dietary constituents. Pharmaceuticals represent a special case. Many have been evaluated, and many are considered to be carcinogenic. Although the main population exposed consists of patients undergoing therapy, there can also be exposure of workers who produce the drugs and of health care workers who administer them. But because the exposure doses are orders of magnitude higher among patients than among workers, we have not listed these as occupational carcinogens. Analogously, we have not listed carcinogenic viruses, notably, human immunodeficiency virus (HIV) and hepatitis B and C viruses, although health care workers may be at risk.

With these criteria, we derived the following lists of occupational carcinogens:

* 28 definite human occupational carcinogens (IARC group 1; Table 3)

* 27 probable human occupational carcinogens (IARC group 2A; Table 4)

* 113 possible human occupational carcinogens (IARC group 2B; Table 5)

* 18 occupations and industries that possibly, probably, or definitely entail excess risk of cancer (IARC groups 1, 2A, and 2B; Table 6).

Tables 3-6 only include agents and circumstances that were reviewed and published by the IARC Monograph Program as of 2003. As discussed above, the evaluations are rooted in the information base that was available at the time of the IARC evaluation. As evidence accumulates, the evaluation of an agent can change, as has already occurred in some cases (e.g., cadmium, acrylonitrile). This is why we have included in the tables a reference to the IARC volume in which the substance was evaluated and its date. Evaluations with early dates are more vulnerable to being out of date.

In a special review published in 1987 (Supplement 7), all substances and occupations covered in the first 15 years of the program were reevaluated (IARC 1987). Thus, every substance for which the Supplement 7 reference is cited had an earlier monograph. For many of the substances, there was little, if any, new information, and consequently, we have quoted the original monograph for those without any new data in 1987. For those substances referenced as Supplement 7, new data were available for the reevaluation,

For the agents in Tables 3-5, we devised a set of subheadings to help the reader digest the long lists of often obscure chemical names: physical agents, respirable dusts and fibers, metals and metal compounds, PAHs, wood and fossil fuels and their by-products, monomers, intermediates in plastics and rubber manufacturing, chlorinated hydrocarbons, aromatic amine dyes, azo dyes, intermediates in the production of dyes, pesticides, nitro compounds, and others. Tables 3-5 indicate some of the main occupations or industries in which each listed substance is found, and the strength of evidence from human and animal studies. In Tables 3 and 4, we show the type(s) of cancer affected, with an indication of the strength of evidence for each type listed. Information on target organ is not shown in Table 5 because, for agents listed as possible carcinogens, evidence concerning humans is either conflicting or not available at all.

For many of the agents listed, but not all, there has been some epidemiologic evidence of carcinogenicity among exposed workers. For most of the agents listed, but not all, the occupational environment represents the most common locale of exposure. The most prominent exceptions to this rule are aflatoxins, sunlight, involuntary, tobacco smoking, and radon. Whether these cause more cases of cancer as a result of occupational or nonoccupational exposure depends on numbers exposed and exposure levels in the two types of milieu. It is plausible that there may be more cases resulting from nonoccupational exposure.

The IARC Monograph Program has occasionally addressed cancer risk in various occupations and industries, as well as agents. However, although the monograph program aims at a systematic evaluation of agents and complex mixtures, it is not intended to provide a systematic review of cancer risk by industries and occupations. That is, those reviews were conducted where there were particular concerns or anticipated insights regarding specific potential carcinogens. Sometimes this was done when there appeared to be strong evidence of risk in an occupation but little indication of what the responsible agent might be (e,g., rubber industry, painters). Sometimes the impetus for an occupation or industry review came from the attempt to evaluate some agent, but it was realized that the evidence regarding that agent was rooted in epidemiologic evidence regarding some occupation or industry (e.g., glass industry, hairdresser). Table 6 shows those occupations and industries that IARC has evaluated as definitely, probably, or possibly entailing a carcinogenic risk. Because there has been no pretense of exhaustiveness in evaluating occupations and industries, the absence of an occupation or industry in Table 6 does not carry the same significance as the absence of an agent in Tables 3-5. That is, it does not signify that there is no known risk for that occupation or industry.

Because our inclusion criteria admitted substances to which workers were exposed in the past, we included some substances that have been banned or virtually eliminated in some countries, such as mustard gas, bis(chloromethyl) ether, tris(2,3-dibromopropyl) phosphate, and 4,4'-methylene bis(2-chloroaniline) (MOCA), as well as some industries that no longer exist (viz. production of auramine and magenta). These are mentioned partly for historic interest and partly because it is possible that these might yet be used in some places at some time.

It is important to note that the substances, occupations, and industries listed in Tables 3-6 are not mutually exclusive. Certainly, some of the occupations and industries listed in Table 6 may be there because of some of the substances that are listed in Tables 3-5. But further, the substances relate to each other in complicated ways. Some families of substances include some specific substances that are also listed (e.g., nonarsenical insecticides, which includes DDT; benzidine-based dyes, which includes benzidine). Also, there are some complex mixtures (e.g., diesel exhaust) that contain a substance on the list (e.g,, nitro-PAHs) that may be responsible for the carcinogenicity of the mixture.

The listing of affected cancer sites in Tables 3 and 4 does not come explicitly from the IARC Monographs. Sometimes the affected target organ(s) was rather evident, but sometimes it required that we evaluate the evidence, including evidence published more recently than the IARC evaluation in question. Table 7 shows the same agents listed in Tables and 4 but organized by site of cancer, Again, we indicate clearly which associations are strong and which are only suggestive. The lung is the target organ that has most often been linked to occupational carcinogens,

The evolution of knowledge. In order to appreciate how knowledge has evolved, we searched for information on the current occupational carcinogens at two earlier time periods. As mentioned above, IARC carried out a comprehensive cumulative synthesis in 1987 (IARC 1987). In that report, the results were presented with the same rating system group 1, 2A, 2B, 3) as is used today, rendering the lists comparable. In 1964, even before the establishment of IARC, the World Health Organization (WHO) commissioned an expert panel to survey available knowledge on human carcinogens (WHO 1964). In the WHO report, there was no explicit rating system, It was a discursive presentation of knowledge and opinions that we attempted, with some license, to translate into a simple system corresponding to definite, probable/possible, or not mentioned. From these two reports, we searched for references to the 168 substances presented in Tables 3-5 and that are currently considered to be definite, probable, or possible occupational carcinogens.

Table 8 shows how the current occupational carcinogens were considered in two earlier times. Half of today's recognized definite occupational carcinogens were already recognized as such by 1964, in the early period of cancer epidemiology. Nearly 90% were considered to be definite or probable as of 15 years ago. In contrast, > 95% of today's probable and possible occupational carcinogens had not even been mentioned as of 1964, and about one-third were not mentioned as of 1987. Although it is possible for the classification of agents to change over time in either direction, in practice there have been rather few instances of agents being "downgraded" between successive periods. Notable counter-examples include the following:

* 3,3-Dichlorobenzene, which was considered a definite carcinogen in 1964 but was only considered as a possible carcinogen as of 1987 and 2002

* Acrylonitrile and propylene oxide, which were considered probable carcinogens in 1987, but only as possible carcinogens in 2002

* Glass wool was considered a possible carcinogen in 1988 but was downgraded to unclassifiable in 2002

* Ionizing radiation, a special case, was considered a definite carcinogen in 1964 and is so considered today, but it had not been reviewed by IARC before the 1990s; therefore, we had to classify it as "unrated" in 1987.

Discussion

Many of the recognized definite occupational carcinogens were first suspected before the era of modern epidemiology (i.e., before 1950). The significance of this observation is unclear. It may be that there were only a limited number of strong occupation-cancer associations, and these were sufficiently obvious that they could produce observable clusters of cases for astute clinicians to notice. It may be that levels of exposure to occupational chemicals were so high before the 1950s as to produce high cancer risks and cancer dusters, but that improvements in industrial hygiene in industrialized countries have indeed decreased risks to levels that are difficult to detect. The number of occupational agents rated by IARC as group 1 carcinogens has tapered off since 1987, whereas the proportion of group 2B evaluations has increased. This reflects the fact that, when the monograph program began, there was a "backlog" of agents for which strong evidence of carcinogenicity had accumulated, and, naturally, these were the agents that IARC initially selected for review. Once the agents with strong evidence had been dealt with, IARC started dealing with others. It would be wrong to infer that the historic trend in IARC designations signals that we are approaching the end of the period of potential to discover occupational carcinogens. There are many thousands of chemicals in workplaces, and new ones are continuously being introduced. Most recognized occupational carcinogens were first suspected on the basis of case reports by clinicians or pathologists (Doll 1975). These discoveries were usually coincidental (Siemiatycki et al. 1981). It is thus reasonable to suspect that there may be some, perhaps many, as yet undiscovered occupational carcinogens. Only a small fraction of occupational agents have been adequately investigated with epidemiologic data. There are many reasons for this including, inter alia, the magnitude of the numbers of agents to be investigated, a shift away from occupational cancer research in the epidemiologic community and into new areas of epidemiologic interest, the difficulty and challenge of exposure assessment, and increasing barriers to accessing human subjects for occupational studies. These are problems that deserve attention, or we will fail in our responsibilities.

Many countries have agencies that list carcinogens. In the United States the two primary sources of information on occupational carcinogens, at least in the form of lists, are NIOSH and the NTP. NIOSH publishes a list of agents that it considers to be occupational carcinogens (NIOSH 2004). Currently there are 133 agents on this list. There is no further information in the NIOSH list regarding the degree of evidence for different agents, the occupations where these may occur or on the target organs, or the criteria and methods used to establish and update this list, The NTP has been mandated under the Public Health Service Act (1978) to maintain a list of human carcinogens and to provide data on each one concerning exposure circumstances and regulatory policies (NTP 2002). This list uses a two-category scale: "known to be a human carcinogen" and "reasonably anticipated to be a human carcinogen." Currently, there are 52 agents listed in the first category and 176 in the second. Information concerning each agent is described in a brief report that includes some exposure data as well as health effects data and regulatory data (NTP 2002). The substances on these lists are not limited to occupational agents, and there is no tabular summary of occupational agents, the occupations in which these may occur, or the target organs. It is beyond the scope of this article to carry out a comparison of the procedures and lists of the various national bodies. Suffice it to say that most of them draw heavily on the IARC program and adapt it to their purposes.

There is sometimes a tendency to interpret tables of carcinogens in too categorical a fashion. Although it may be convenient for lobbyists and regulators to divide the world of chemicals and occupational circumstances into "good guys" and "bad guys," such a dichotomy is simplistic. The determination that a substance or circumstance is carcinogenic depends on the strength of evidence at a given point in time. The evidence is sometimes clear-cut (which would correspond to evaluations of group 1 or group 4), but more often it is not. The balance of evidence can change in either direction as new data emerge.

The characterization of an occupation or industry group as a "high-risk group" is strongly rooted in time and place. For instance, the fact that some groups of nickel refinery workers experienced excess risks of nasal cancer does not imply that all workers in all nickel refineries will be subject to such risks. The particular circumstances of the industrial process, raw materials, impurities, and control measures may produce risk in one nickel refinery but not in another or in one historic era but not in another. The same can be said of rubber production facilities, aluminum refineries, and other industries and occupations. Labeling a chemical substance as a carcinogen in humans is a more timeless statement than labeling an occupation or industry as a high-risk group. However, even such a statement requires qualification. Different carcinogens produce different levels of risk, and for a given carcinogen there may be vast differences in the risks incurred by different people exposed under different circumstances. Indeed, there may be threshold effects or interactions with other factors, environmental or genetic, that produce no risk for some exposed workers and high risk for others.

This raises the issue of quantitative risk assessment, which is an important tool in prevention of occupational cancer. Unfortunately, our tables provide no basis for gauging the strength of the effect of each carcinogen, either in relative risk terms or in absolute risk

terms, or in terms of dose-response relationships. The IARC evaluations provide no such indications, and although it would be most desirable to have such information, for most agents the information base to support such quantification is fragmentary.

In summary, the listing of occupational carcinogens is important. It provides a yardstick of our knowledge base, it provides guidance in setting research priorities, and it provides an important tool for prevention of cancer. Regulatory procedures and other aspects of cancer prevention depend on the listing of carcinogens. The IARC Monograph Program has been an indispensable component of this process. The tables presented herein, based on IARC Monographs but augmented in various ways, will be useful to researchers in setting research priorities and in furthering our understanding of carcinogenesis, and to those interested in preventing occupational cancer.

Table 1. Classifications used in the IARC Monographs to characterize
evidence of carcinogenicity.

Category of evidence                       In humans

Sufficient evidence       A causal relationship has been established
of carcinogenicity        between exposure to the agent, mixture, or
                          exposure circumstances 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       A positive association has been observed
carcinogenicity           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.

Insufficient evidence     The available studies are of insufficient
of carcinogenicity        quality, consistency, or statistical power
                          to permit a conclusion regarding the
                          presence or absence of a causal association
                          between exposure and cancer, or no data on
                          cancer in humans are available.

Evidence suggesting       There are several adequate studies covering
lack of carcinogenicity   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, mixture, or exposure circumstance and
                          any studied cancer at any observed level of
                          exposure.

Category of evidence                       In animals

Sufficient evidence       A causal relationship has been established
of carcinogenicity        between the agent or mixture and an
                          or ofan appropriate combination of benign
                          and malignant neoplasms in increased
                          incidence of malignant neoplasms in a) two
                          or more species of animals or b) in two or
                          more independent studies in one species
                          carried out at different times or in
                          different laboratories or under different
                          protocols.

Limited evidence of       The data suggest a carcinogenic effect but
carcinogenicity           are limited for making a definitive
                          evaluation because, for example, a) the
                          evidence of carcinogenicity is restricted to
                          a single experiment; b) there are unresolved
                          questions regarding the adequacy of the
                          design, conduct, or interpretation of the
                          study, or c) the agent or mixture increases
                          the incidence only of benign neoplasms or
                          lesions of uncertain neoplastic potential,
                          or of certain neoplasms that may occur
                          spontaneously in high incidences in certain
                          strains.

Insufficient evidence     The studies cannot be interpreted showing
of carcinogenicity        either the presence or absence of a
                          carcinogenic effect because of major
                          qualitative or quantitative limitations, or
                          no data on cancer in experimental animals
                          are available.

Evidence suggesting       Adequate studies involving at least two
lack of carcinogenicity   species are available which show that,
                          within the limits of the tests used, the
                          agent or mixture is not carcinogenic.

Table 2. Guidelines used by the IARC Monographs Program in evaluating
human carcinogenicity based on the synthesis of epidemiologic, animal,
and other evidence. (a)

                                               Combinations that fit
                                                    in the group

Group          Description of group           Epidemiologic evidence

1       The agent, mixture, or exposure             Sufficient
        circumstance is carcinogenic
        to humans                              Less than sufficient

2A      The agent, mixture, or exposure              Limited
        circumstance is probably
        carcinogenic to humans
                                                Inadequate or not
                                                    available

2B      The agent, mixture, or exposure              Limited
        circumstance is possibly
        carcinogenic to humans                  Inadequate or not
                                                    available

                                                Inadequate or not
                                                    available

3       The agent, mixture, or exposure         Inadequate or not
        circumstance is not classifiable as         available
        to its carcinogenicity to humans

4       The agent, mixture, or exposure         Suggesting lack of
        circumstance is probably not             carcinogenicity
        carcinogenic to humans
                                                Inadequate or not
                                                    available

                                              Combinations that fit in
                                                     this group

Group   Description of group                      Animal evidence

1       The agent, mixture, or exposure                 Any
        circumstance is carcinogenic
        to humans                                    Sufficient

2A      The agent, mixture, or exposure              Sufficient
        circumstance is probably
        carcinogenic to humans
                                                     Sufficient

2B      The agent, mixture, or exposure         Less than sufficient
        circumstance is possibly
        carcinogenic to humans                       Sufficient

                                                      Limited

3       The agent, mixture, or exposure               Limited
        circumstance is not classifiable as
        to its carcinogenicity to humans
                                              Not elsewhere classified

4       The agent, mixture, or exposure          Suggesting lack of
        circumstance is probably not              carcinogenicity
        carcinogenic to humans
                                                 Suggesting lack of
                                                  carcinogenicity

                                              Combinations that
                                                 fit in this
                                                    group

Group   Description of group                   Other evidence

1       The agent, mixture, or exposure              Any
        circumstance is carcinogenic
        to humans                             Strongly positive

2A      The agent, mixture, or exposure           Less than
        circumstance is probably              strongly positive
        carcinogenic to humans
                                              Strongly positive

2B      The agent, mixture, or exposure              Any
        circumstance is possibly
        carcinogenic to humans                    Less than
                                              strongly positive

                                              Strongly positive

3       The agent, mixture, or exposure           Less than
        circumstance is not classifiable as   strongly positive
        to its carcinogenicity to humans

4       The agent, mixture, or exposure              Any
        circumstance is probably not
        carcinogenic to humans
                                                  Strongly
                                                  negative

(a) This table shows our interpretation of the IARC Monographs
Program guidelines to derive the overall evaluation from the
combined epidemiologic, animal, and other evidence. However,
the IARC working groups can, under exceptional circumstances,
depart from these guidelines in deriving the overall evaluation
(IARC 2003). For example, the overall evaluation can be
downgraded if there is less than sufficient evidence in humans
and strong evidence that the mechanism operating in animals is
not relevant to humans.

Table 3. Substances and mixtures that have been evaluated by IARC
as definite (group 1) human carcinogens and that are occupational
exposures.

                                    Occupation or industry in which
Substance or mixture                  the substance is found (a)

Physical agents
  Ionizing radiation and sources   Radiologists, technologists,
    thereof, including, notably,     nuclear workers, radium-dial
    X rays, [gamma] rays,            painters; underground miners,
    neutrons, and radon gas          plutonium workers, cleanup
                                     workers following nuclear
                                     accidents, aircraft crew
  Solar radiation                  Outdoor workers

Respirable dusts and fibers
  Asbestos                         Mining and milling, by-product
                                     manufacture, insulating,
                                     shipyard workers; sheet-metal
                                     workers, asbestos cement
                                     industry
  Erionite                         Waste treatment, sewage,
                                     agricultural waste, air
                                     pollution control systems;
                                     cement aggregates, building
                                     materials
  Silica, crystalline              Granite and stone industries,
                                     ceramics, glass, and related
                                     industries, foundries and
                                     metallurgical industries,
                                     abrasives; construction;
                                     farming
  Talc containing                  Manufacture of pottery, paper,
    asbestiform fibers               paint, and cosmetics
  Wood dust                        Logging and sawmill workers, pulp
                                     and paper and paperboard
                                     industry, woodworking trades
                                     (e.g., furniture industries,
                                     cabinetmaking, carpentry and
                                     construction); used as filler
                                     in plastic and linoleum
                                     production
Metals and metal compounds
  Arsenic and arsenic              Nonferrous metal smelting;
    compounds                        production, packaging, and use
                                     of arsenic-containing
                                     pesticides, sheep dip
                                     manufacture, wool fiber
                                     production, mining of ores
                                     containing arsenic
  Beryllium                        Beryllium extraction and
                                     processing, aircraft and
                                     aerospace industries;
                                     electronics and nuclear
                                     industries; jewelers
  Cadmium and cadmium              Cadmium-smelter workers, battery
    compounds                        production workers, cadmium-
                                     copper alloy workers, dyes and
                                     pigments production;
                                     electroplating processes
  Chromium compounds,              Chromate production plants, dyes
    hexavalent                       and pigments, plating and
                                     engraving, chromium ferro-alloy
                                     production, stainless-steel
                                     welding, in wood preservatives,
                                     leather tanning, water
                                     treatment, inks, photography,
                                     lithography, drilling muds,
                                     synthetic perfumes,
                                     pyrotechnics, corrosion
                                     resistance
  Selected nickel compounds,       Nickel refining and smelting;
    including combinations of        welding
    nickel oxides and sulfides
    in the nickel refining
    industry
Wood and fossil fuels and their
    by-products
  Benzene                          Production; solvents in the shoe
                                     production industry, chemical,
                                     pharmaceutical, and rubber
                                     industries, printing industry
                                     (rotogravure plants, bindery
                                     departments), gasoline additive
  Coal tars and pitches            Production of refined chemicals
                                     and coal tar products (patent-
                                     fuel), coke production; coal
                                     gasification, aluminum
                                     production, foundries, road
                                     paving and construction
                                     (roofers and slaters)
  Mineral oils, untreated          Production; used as lubricant by
    and mildly treated               metal workers, machinists,
                                     engineers; printing industry
                                     (ink formulation), used in
                                     cosmetics, medicinal and
                                     pharmaceutical preparations
  Shale oils or shale-derived      Mining and processing; used as
    lubricants                       fuels or chemical-plant
  Soots                              feedstocks:lubricant in cotton
                                     textile industry
                                   Chimney sweeps, heating-unit
                                     service personnel; brick masons
                                     and helpers, building
                                     demolition workers, insulators,
                                     firefighters, metallurgical
                                     workers, work involving burning
                                     of organic materials
Monomers
  Vinyl chloride                   Production; production of poly
                                     vinyl chloride and co-polymers;
                                     refrigerant before 1974,
                                     extraction solvent; in aerosol
                                     propellants
Intermediates in plastics and
    rubber manufacturing
  Bis(chloromethyl) ether and      Production; chemical
    chloromethyl methyl ether        intermediate; alkylating agent,
    (technical grade)                laboratory reagent; plastic
                                     manufacturing, ion-exchange
                                     resins and polymers
Aromatic amine dyes
  4-Aminobiphenyl                  Production; dyestuffs and pigment
                                     manufacture
  Benzidine                        Production; dyestuffs and pigment
                                     manufacture
  2-Naphthylamine                  Production, dyestuffs and pigment
                                     manufacture
Pesticides
  Ethylene oxide                   Production; chemical industry;
                                     sterilizing agent (hospitals,
                                     spice fumigation)
  2,3,7,8-Tetrachlorodibenzo-      Production; use of chlorophenols
    para-dioxin (TCDD)               and chlorophenoxy herbicides;
                                     waste incineration; PCB
                                     production, pulp and paper
                                     bleaching

Others
  Aflatoxin                        Feed production industry; workers
                                     loading and unloading cargo;
                                     rice and maize processing
  Involuntary (passive) smoking    Workers in bars and restaurants,
                                     office workers
  Mustard gas                      Production; used in research
                                     laboratories; military
                                     personnel
  Strong inorganic-acid mists      Pickling operations; steel
    containing sulfuric acid         industry; petrochemical
                                     industry, phosphate acid
                                     fertilizer manufacturing

                                    IARC Monograph        Human
Substance or mixture               volume (year) (b)   evidence (c)

Physical agents
  Ionizing radiation and sources    Vol. 75 (2000a)     Sufficient
    thereof, including, notably,    Vol. 78 (2001a)
    X rays, [gamma] rays,
    neutrons, and radon gas
  Solar radiation                   Vol. 55 (1992b)     Sufficient
Respirable dusts and fibers
  Asbestos                          Suppl. 7 (1987)     Sufficient
  Erionite                          Suppl. 7 (1987)     Sufficient
  Silica, crystalline               Vol. 68 (19975)     Sufficient
  Talc containing                   Suppl. 7 (1987)     Sufficient
    asbestiform fibers
  Wood dust                         Vol. 62 (1995b)     Sufficient
Metals and metal compounds
  Arsenic and arsenic               Suppl. 7 (1987)     Sufficient
    compounds
  Beryllium                         Vol. 58 (1993a)     Sufficient
  Cadmium and cadmium               Vol. 58 (1993a)     Sufficient
    compounds
  Chromium compounds,               Vol. 49 (1990a)     Sufficient
    hexavalent
  Selected nickel compounds,        Vol. 49 (1990a)     Sufficient
    including combinations of
    nickel oxides and sulfides
    in the nickel refining
    industry
Wood and fossil fuels and their
    by-products
  Benzene                           Suppl. 7 (1987)     Sufficient
  Coal tars and pitches             Suppl. 7 (1987)     Sufficient
  Mineral oils, untreated           Suppl. 7 (1987)     Sufficient
    and mildly treated
  Shale oils or shale-derived       Suppl. 7 (1987)     Sufficient
    lubricants
  Soots                             Vol. 35 (1985)      Sufficient
Monomers
  Vinyl chloride                    Suppl. 7 (1987)     Sufficient
Intermediates in plastics and
    rubber manufacturing
  Bis(chloromethyl) ether and       Suppl. 7 (1987)     Sufficient
    chloromethyl methyl ether
    (technical grade)
Aromatic amine dyes
  4-Aminobiphenyl                   Suppl. 7 (1987)     Sufficient
  Benzidine                         Suppl. 7 (1987)     Sufficient
  2-Naphthylamine                   Suppl. 7 (1987)     Sufficient
Pesticides
  Ethylene oxide                    Vol. 60 (1994)       Limited
  2,3,7,8-Tetrachlorodibenzo-       Vol. 69 (1997a)      Limited
    para-dioxin (TCDD)
Others
  Aflatoxin                         Vol. 82 (2002b)     Sufficient
  Involuntary (passive) smoking     Vol. 83 (2004)      Sufficient
  Mustard gas                       Suppl. 7 (1987)     Sufficient
  Strong inorganic-acid mists       Vol. 54 (1992a)     Sufficient
    containing sulfuric acid

                                      Animal
Substance or mixture               evidence (c)         Site(s)

Physical agents
  Ionizing radiation and sources    Sufficient         Bone (d)
    thereof, including, notably,                     Leukemia (d)
    X rays, [gamma] rays,                              Lung (d)
    neutrons, and radon gas                            Liver (d)
                                                      Thyroid (d)
                                                      Others (d)
  Solar radiation                   Sufficient       Melanoma (d)
                                                       Skin (d)
Respirable dusts and fibers
  Asbestos                          Sufficient         Lung (d)
                                                   Mesothelioma (d)
                                                      Larynx (e)
                                                     GI tract (e)
  Erionite                          Sufficient     Mesothelioma (d)
  Silica, crystalline               Sufficient         Lung (d)
  Talc containing                   Inadequate         Lung (d)
    asbestiform fibers                             Mesothelioma (d)
  Wood dust                         Inadequate      Nasal cavities
                                                     and paranasal
                                                      sinuses (d)
Metals and metal compounds
  Arsenic and arsenic                Limited           Skin (d)
    compounds                                          Lung (d)
                                                         Liver
                                                  (angiosarcoma) (e)
  Beryllium                         Sufficient         Lung (d)
  Cadmium and cadmium               Sufficient         Lung (d)
    compounds
  Chromium compounds,               Sufficient         Lung (d)
    hexavalent                                     Nasal sinuses (e)
  Selected nickel compounds,        Sufficient         Lung (d)
    including combinations of                        Nasal cavity
    nickel oxides and sulfides                      and sinuses (d)
    in the nickel refining
    industry
Wood and fossil fuels and their
    by-products

  Benzene                            Limited         Leukemia (d)
  Coal tars and pitches             Sufficient         Skin (d)
                                                       Lung (e)
                                                      Bladder (e)
  Mineral oils, untreated           Inadequate         Skin (d)
    and mildly treated                                Bladder (e)
                                                       Lung (e))
                                                   Nasal sinuses (e)
  Shale oils or shale-derived       Sufficient         Skin (d)
    lubricants
  Soots                             Inadequate         Skin (d)
                                                       Lung (d)
                                                     Esophagus (e)
Monomers
  Vinyl chloride                    Sufficient           Liver
                                                  (angiosarcoma) (d)
                                                         Liver
                                                       (hepato-
                                                     cellular) (e)
Intermediates in plastics and
    rubber manufacturing
  Bis(chloromethyl) ether and       Sufficient    Lung (oat cell) (d)
    chloromethyl methyl ether
    (technical grade)
Aromatic amine dyes
  4-Aminobiphenyl                   Sufficient        Bladder (d)
  Benzidine                         Sufficient        Bladder (d)
  2-Naphthylamine                   Sufficient        Bladder (d)
Pesticides
  Ethylene oxide                    Sufficient       Leukemia (d)
  2,3,7,8-Tetrachlorodibenzo-       Sufficient         All sites
    para-dioxin (TCDD)                               combined (d)
                                                       Lung (e)
                                                      Non-Hodgkin
                                                     lymphoma (e)
                                                      Sarcoma (e)
Others
  Aflatoxin                         Sufficient         Liver (d)
  Involuntary (passive) smoking     Sufficient         Lung (d)
  Mustard gas                        Limited          Larynx (d)
                                                       Lung (e)
                                                      Pharynx (e)
  Strong inorganic-acid mists          Not            Larynx (d)
    containing sulfuric acid        available          Lung (e)

(a) Not necessarily an exhaustive list of occupations/industries
in which this agent is found; not all workers in these occupations/
industries are exposed. The term "production" is used to indicate
that this substance is man-made and that workers may be exposed in
the production process. (b) Most recent IARC evaluation; for those
referenced to Supplement 7 (IARC 1987), it is possible that the
1987 review was quite perfunctory and that the essential evidence
was cumulated at an earlier date. (c) As judged by the IARC working
group; we added the notation "not available" to signify those
substances for which there was no evidence at all. (d) We judged
that evidence for an association with this site was strong. (e) We
judged that evidence was suggestive.

Table 4. Substances and mixtures that have been evaluated by
IARC as probable (group 2A) human carcinogens and that are
occupational exposures.

                                    Occupation or industry in which
Substance or mixture                  the substance is found (a)

Physical agents
  Ultraviolet radiation          Arc welding, industrial
    (A, B, and C) from             photoprocesses, sterilization and
    artificial sources             disinfection; phototherapy,
                                   operating theaters, research
                                   laboratories; ultraviolet
                                   fluorescence in food industry;
                                   insect traps
Polyaromatic hydrocarbons
  Benz[a]anthracene              Work involving combustion of organic
                                   matter, foundries; steel mills,
                                   firefighters, vehicle mechanics
  Benzo[a]pyrene                 Work involving combustion of organic
                                   matter; foundries; steel mills;
                                   firefighters; vehicle mechanics
  Dibenz[a,h]anthracene          Work involving combustion of organic
                                   matter, foundries, steel mills,
                                   firefighters, vehicle mechanics
Wood and fossil fuels and
    their by-products
  Creosotes                      Brickmaking, wood preserving
  Diesel engine exhaust          Railroad workers, professional
                                   drivers, dock workers, mechanics
Intermediates in plastics and
    rubber manufacturing
  4,4 -Methylene bis(2-          Production, curing agent for roofing
    chloroaniline)                 and wood sealing
  Styrene-7,8-oxide              Production; styrene glycol
                                   production, perfume preparation;
                                   reactive diluent in epoxy resin
                                   formulations, as chemical
                                   intermediate for cosmetics, surface
                                   coating, and agricultural and
                                   biological chemicals, used for
                                   treatment of fibers and textiles;
                                   in fabricated rubber products
Chlorinated hydrocarbons
  [alpha]-Chlorinated toluenes   Production; dye and pesticide
                                   manufacture
  Polychlorinated biphenyls      Production, electrical capacitor
                                   manufacturing
  Tetrachloroethylene            Production; dry cleaning; metal
                                   degreasing
  Trichlomethylene               Production, dry cleaning; metal
                                   degreasing
Monomers
  Acrylamide                     Chemical industry; water and
                                   wastewater treatment; textile,
                                   steel, and lumber industries;
                                   petroleum refining, mineral
                                   processing; sugar production,
                                   hospitals
  1,3-Butadiene                  Chemical and rubber industries
  Epichlorohydrin                Production and use of resins,
                                   glycerine, and propylene-based
                                   rubbers, used as a solvent
  Vinyl bromide                  Production; production of vinyl
                                   bromide polymers and monoacrylic
                                   fibers for carpet backing material,
                                   rubber and plastic production
  Vinyl fluoride                 Production, polyvinyl fluoride and
                                   fluoropolymer production
Aromatic amine dyes
  Benzidine-based dyes           Production, used in textile, paper,
                                   leather, rubber, plastics,
                                   printing, paint, and lacquer
                                   industries
  4-Chloro-ortho-toluidine       Dye and pigment manufacture;
                                   textile industry
  ortho-Toluidine                Production, manufacture of dyestuffs,
                                   pigments, optical brightener,
                                   pharmaceuticals, and pesticides;
                                   rubber vulcanizing; clinical
                                   laboratory reagent, cleaners and
                                   janitors
Intermediates in the
    production of dyes
  Dimethylcarbamoyl chloride     Production; manufacture of
                                   pharmaceuticals, pesticides, and
                                   dyes
Pesticides
  Captafol                       Production; fungicide
  Ethylene dibromide             Production, pest control, petroleum
                                   refining and waterproofing, leaded
                                   gasoline additive; chemical inter-
                                   mediate and solvent in gums, waxes,
                                   resins, dyes, and pharmaceutical
                                   preparations
  Nonarsenical insecticides      Production, pest control and
                                   agricultural workers; flour and
                                   grain mill workers
Others
  Diethyl sulfate                Ethanol production
  Formaldehyde                   Production; pathologists, medical
                                   laboratory technicians; plastics;
                                   textile industry
  Tris)(2,3-dibromopropyl)       Production, used in the textile
                                   phosphate industry, in phenolic
                                   resins (for electronics industry),
                                   paints, paper coatings, and rubber

                                  IARC Monograph         Human
Substance or mixture             volume (year) (b)   evidence (c)

Physical agents
  Ultraviolet radiation           Vol. 55 (1992b)     Inadequate
    (A, B, and C) from
    artificial sources
Polyaromatic hydrocarbons
  Benz[a]anthracene               Vol. 32 (1983b)    Not available
  Benzo[a]pyrene                  Vol. 32 (1983b)    Not available
  Dibenz[a,h]anthracene           Vol. 32 (1983b)    Not available
Wood and fossil fuels and
    their by-products
  Creosotes                       Vol. 35 (1985)        Limited
  Diesel engine exhaust           Vol. 46 (1989a)       Limited
Intermediates in plastics and
    rubber manufacturing
  4,4 -Methylene bis(2-           Vol. 57 (1993b)     Inadequate
    chloroaniline)
  Styrene-7,8-oxide               Vol. 60 (1994)      Inadequate
Chlorinated hydrocarbons
  [alpha]-Chlorinated toluenes    Vol. 71 (1999a)       Limited
  Polychlorinated biphenyls       Suppl. 7 (1987)       Limited
  Tetrachloroethylene             Vol. 63 (1995a)       Limited
  Trichlomethylene                Vol. 63 (1995a)       Limited
Monomers
  Acrylamide                      Vol. 60 (1994)      Inadequate
  1,3-Butadiene                   Vol. 71 (1999a)       Limited
  Epichlorohydrin                 Vol. 71 (1999a)     Inadequate
  Vinyl bromide                   Vol. 71 (1999a)    Not available
  Vinyl fluoride                  Vol. 63 (1995a)    Not available
Aromatic amine dyes
  Benzidine-based dyes            Suppl. 7 (1987)     Inadequate
  4-Chloro-ortho-toluidine        Vol. 77 (2000b)       Limited
  ortho-Toluidine                 Vol. 77 (2000b)       Limited
Intermediates in the
    production of dyes
  Dimethylcarbamoyl chloride      Vol. 71 (1999a)     Inadequate
Pesticides
  Captafol                        Vol. 53 (1991b)    Not available
  Ethylene dibromide              Vol. 71 (1999a)     Inadequate
  Nonarsenical insecticides       Vol. 53 (1991b)       Limited
Others
  Diethyl sulfate                 Vol. 71 (1999a)    Not available
  Formaldehyde                    Vol. 62 (1995b)       Limited
  Tris)(2,3-dibromopropyl)        Vol. 71 (1999a)     Inadequate

                                    Animal
Substance or mixture             evidence (c)         Site(s)

Physical agents
  Ultraviolet radiation           Sufficient       Melanoma (d)
    (A, B, and C) from
    artificial sources
Polyaromatic hydrocarbons
  Benz[a]anthracene               Sufficient         Lung (d)
                                                    Bladder (d)
                                                     Skin (d)
  Benzo[a]pyrene                  Sufficient         Lung (d)
                                                    Bladder (d)
                                                     Skin (d)
  Dibenz[a,h]anthracene           Sufficient         Lung (d)
                                                    Bladder (d)
                                                     Skin (d)
Wood and fossil fuels and
    their by-products
  Creosotes                       Sufficient         Skin (d)
  Diesel engine exhaust           Sufficient         Lung (d)
                                                    Bladder (d)
Intermediates in plastics and
    rubber manufacturing
  4,4 -Methylene bis(2-           Sufficient        Bladder (d)
    chloroaniline)
  Styrene-7,8-oxide               Sufficient
Chlorinated hydrocarbons
  [alpha]-Chlorinated toluenes    Sufficient         Lung (d)
  Polychlorinated biphenyls       Sufficient     Liver and biliary
                                                     tract (d)
  Tetrachloroethylene             Sufficient        Cervix (d)
                                                   Esophagus (d)
                                                    Non-Hodgkin
                                                   lymphoma (d)
  Trichlomethylene                Sufficient         Liver and
                                                 biliary tract (d)
                                                    Non-Hodgkin
                                                   lymphoma (d)
                                                  Renal cell (d)
Monomers
  Acrylamide                      Sufficient       Pancreas (d)
  1,3-Butadiene                   Sufficient          Lympho-
                                                 hematopoietic (d)
  Epichlorohydrin                 Sufficient         Lung (d)
                                                      CNS (d)
  Vinyl bromide                   Sufficient
  Vinyl fluoride                  Sufficient
Aromatic amine dyes
  Benzidine-based dyes            Sufficient        Bladder (d)
  4-Chloro-ortho-toluidine        Sufficient        Bladder (d)
  ortho-Toluidine                 Sufficient        Bladder (d)
Intermediates in the
    production of dyes
  Dimethylcarbamoyl chloride      Sufficient
Pesticides
  Captafol                        Sufficient
  Ethylene dibromide              Sufficient
  Nonarsenical insecticides      Not available       Brain (d)
                                                   Leukemia (d)
                                                     Lung (d)
                                                     Multiple
                                                    myeloma (d)
                                                    Non-Hodgkin
                                                   lymphoma (d)
Others
  Diethyl sulfate                 Sufficient
  Formaldehyde                    Sufficient       Leukemia (d)
                                                 Nasal sinuses (d)
                                                  Nasopharynx (d)
  Tris)(2,3-dibromopropyl)        Sufficient

CNS, central nervous system.

(a) Not necessarily an exhaustive list of occupations/industries
in which this agent is found; not all workers in these occupations/
industries are exposed. The term "production" is used to indicate
that this substance is man-made and that workers may be exposed in
the production process. (b) Most recent IARC evaluation; for those
referenced as Supplement 7 (IARC 1987), it is possible that the
1987 review was quite perfunctory and that the essential evidence
was cumulated at an earlier date. (c) As judged by the IARC working
group; we added the notation "not available" to signify those
substances for which there was no epidemiologic evidence at all.
(d) We judged that the evidence was suggestive.

Table 5. Substances and mixtures that have been evaluated by IARC
as possible (group 2B) human carcinogens and that are occupational
exposures.

                                    Occupation or industry in which
Substance or mixture                  the substance is found (a)

Respirable dusts and fibers
  Glass wool                     Production, construction and
                                   insulation
  Palygorskite (long fibers      Miners and millers; production of
    > 5 [micro]m)                  waste absorbents, fertilizers, and
                                   pesticides
  Refractory ceramic fibers      Production, furnace insulators; ship
                                   builders; heat-resistant fabric
                                   manufacture
  Rock wool                      Production; thermal or acoustical
                                   insulation
  Slag wool fireproofing         Production, thermal or acoustical
                                   insulation
  Special-purpose glass fibers   Reinforced plastic industry
    such as E-glass and "475"
    glass fibers
Metals and metal compounds
  Antimony trioxide              Ore processing; glass and ceramic
                                   production
  Cobalt and cobalt compounds    Miners; processing of copper and
                                   nickel ore; glass and ceramic
                                   production
  Lead and inorganic lead        Lead smelters, plumbers; solderers;
    compounds                      occupations in battery recycling
                                   smelters
  Methyl mercury compounds       Pesticide and fungicide production;
                                   paint industry
  Nickel: metallic and alloys    Nickel miners, metal fabrication,
                                   grinding, electroplating, and
                                   welding
Wood and fossil fuels and
    their by-products
  Benzofuran                     Production, intermediate in
                                   coumarone-indene resin poly
                                   merization, coke production; coal
                                   gasification and combustion
  Bitumens, extracts of steam-   Production/refining, road
    refined and air-refined        construction, roofing and flooring
  Carbon black                   Production; paint, ink, plastic and
                                   rubber industries
  Diesel fuel, marine            Petroleum refineries; marine fuel;
                                   distribution
  Fuel oils, residual (heavy)    Petroleum refineries, distribution,
                                   marine fleets, most large diesel
                                   engines operated on land,
                                   industrial heating systems
  Gasoline                       Petroleum refineries, transportation,
                                   mechanics and service station
                                   attendants
  Gasoline engine exhaust        Transportation and vehicle
                                   maintenance workers, drivers; toll
                                   attendants, traffic controllers
  Naphthalene                    Production, insecticide, resin, and
                                   pharmaceutical production
Polyaromatic hydrocarbons
  Benzo[b]fluoranthene           Work involving combustion of organic
                                   matter
  Benzo[j]fluoranthene           Work involving combustion of organic
                                   matter
  Benzo[k]fluoranthene           Work involving combustion of organic
                                   matter
  Dibenz[a,h]acridine            Production; used in dye synthesis;
                                   biochemical laboratory workers;
                                   work involving combustion of
                                   organic matter
  Dibenz[a,j]acridine            Production; dye synthesis; work
                                   involving combustion of organic
                                   matter
  Dibenzo[a,e]pyrene             Production; biochemical laboratory
                                   workers, work involving combustion
                                   of organic matter
  Dibenzo[a,h]pyrene             Production, biochemical laboratory
                                   workers, work involving combustion
                                   of organic matter
  Dibenzo[a,i]pyrene             Work involving combustion of organic
                                   matter
  Dibenzo[a,4pyrene              Production, biochemical laboratory
                                   workers, work involving combustion
                                   of organic matter
Monomers
  Acrylonitrile                  Production; acrylic textile fiber and
                                   plastic production
  Chloroprene                    Production; manufacture of poly-
                                   chloroprene (synthetic rubber)
  Ethyl acrylate                 Production; plastic molding
                                   occupations using acrylate resins
  Isoprene                       Production, synthetic rubber and
                                   plastics industries
  Styrene                        Polyester resin manufacture,
                                   production of packaging materials
                                   and fiberglass-reinforced polyester
  Toluene diisocyanates          Production, production of
                                   polyurethane foams and wire
                                   coating; insulation workers, ship
                                   builders
  Urethane                       Production; amino-resin production
  Vinyl acetate                  Production; plastics, paint, and
                                   adhesive industries
Intermediates in plastics and
    rubber manufacturing
  Acetaldehyde                   Acetic acid production workers,
                                   dyestuff, plastic and synthetic
                                   rubber industries
  Acetamide                      Production, plastics and chemical
                                   industries
  2,4-Diaminotoluene             Production, chemical intermediate in
                                   TDI production; dyes for textiles;
                                   leather, furs; wood; biologic
                                   stain, photo developer
  1,2-Epoxybutane                Production, metal degreasing;
                                   plastics industry
  Ethylbenzene                   Production; ink, paint, and plastic
                                   production
  Ethylene thiourea              Production, vulcanization in the
                                   rubber industry, manufacture of
                                   ethylenebisdithiocarbamate
                                   pesticides; electroplating baths,
                                   dyes, pharmaceuticals, synthetic
                                   resins
  Phenyl glycidyl ether          Production; epoxy resins; casting and
                                   molding
  Propylene oxide                Production, polyurethane foam and
                                   glycol production, fumigant
Chlorinated hydrocarbons
  Carbon tetrachloride           Production; industrial degreasing
                                   occupations; dry cleaners,
                                   refrigerant production
  Chlorinated paraffin of        Production, polyvinyl chloride
    average carbon-chain           processing industry
    length C12
  Chloroform                     Refrigerant production; dyes,
                                   solvents, and pesticides
  1,2-Dichloroethane             Vinyl chloride production workers
  Dichloromethane                Production, painters and furniture
                                   restorers, pharmaceutical and
                                   electronic production
  Hexachloroethane               Production, aluminum refinery,
                                   industrial firefighters
Aromatic amine dyes
  Auramine (technical grade)     Production; textiles, plastic, and
                                   printing
  Benzyl violet 4B               Production; food; drugs; cosmetics;
                                   textiles
  CI Basic Red 9                 Production, textiles, printing,
                                   biologic stains (basic fuchsin dye
                                   in laboratories)
  2,4-Diaminoanisole             Dyestuff industry; barbers and
                                   cosmetologists, furriers
  3,3'-Dimethylbenzidine         Production; dye or intermediate in
    (o-tolidine)                   dye and pigment production;
                                   polyurethane elastomers, coating,
                                   plastics; clinical laboratories
  2,6-Dimethylaniline            Production; dyestuffs and
    (2,6-xylidine)                 pharmaceutical manufacturing
  3,3'-Dichlorobenzidine         Production; dyestuff manufacturing
  4,4'-Diaminodiphenyl ether     Production; polyamide-type resin
                                   manufacturing
  Disperse Blue 1                Production; hair coloring, textiles
                                   and plastics
  HC Blue No. 1                  Production; hair dye
  4,4'-Methylenedianiline        Production, production of
                                   diisocyanates, polyisocyanates,
                                   and epoxy resins
  Magenta containing             Production; textiles and printing,
    CI Basic Red 9                 biologic stains in laboratories,
                                   photography
Azo dyes
  ortho-Aminoazotoluene          Production; textiles and leather
  para-Aminoazobenzene           Production; textiles and leather
  CI Acid Red 114                Production; textiles and leather
  CI Direct Blue 15              Production; textiles and paper
  Citrus Bed No. 2               Production; used for food coloring
  para-Dlmethylaminoazobenzene   Production; textiles; laboratories
  Oil orange SS                  Production, dyes/pigments for
                                   varnishes, oils, fats, and waxes
  Ponceau 3R                     Production; textiles
  Ponceau MX                     Production, textiles, leather, inks;
                                   paper; wood stains; food, biology
                                   laboratories
  Trypan blue                    Production, textiles and printing,
                                   biologic stains in life science
                                   laboratories, used by
                                   ophthalmologists
Intermediates for the
    manufacture of dyes
  para-Cresidine                 Production, manufacture of dyes,
                                   pigments, and perfumes
  3,3'-Dimethoxybenzidine        Production; manufacture of dyes and
    (ortho-dianisidine)            pigments; dye for leather, paper,
                                   plastics, rubber, textiles, and
                                   laboratories
  2-Methyl-1-nitro               Production, synthesis of
    anthraquinone (of              anthraquinone dyes
    uncertain purity/impurity)
  4,4'-Methylene bis (2-         Production, manufacture of dyes and
    methylaniline)                 pigments
  2-Nitroanisole                 Production, manufacture of the dye
                                   intermediates ortho-anisidine and
                                   ortho-dianisidine
  4,4'-Thiodianiline             Production, manufacture of dyes
Nitro compounds
  2,4-Dinitrotoluene             Production; manufacture of
                                   diisocyanates and munitions
  2,6-Dinitrotoluene             Production; manufacture of
                                   diisocyanates and munitions
  Nitrobenzene                   Production, manufacture of dyestuffs,
                                   detergents, and cosmetics
  2-Nitrofluorene                Underground miners using diesel-
                                   powered machinery
  2-Nitropropane                 Production; ink, paint, explosives
                                   industries
  1-Nitropyrene                  Production, manufacture of
                                   azidopyrene, particulate emissions
  4-Nitropyrene                  Production; used only as a laboratory
                                   chemical, probably present before
                                   1980 in carbon black used in
                                   photocopy machines
  Tetranitromethane              Production, diesel fuel additive, TNT
                                   manufacturing
Pesticides
  Aramite                        Production, in miticides in
                                   greenhouses, nurseries, and
                                   orchards
  Chlordane                      Production; termite control
  Chlordecone                    Production; insecticide
  Chlorophenoxy herbicides       Production; defoliant
  Chlorothalonil                 Production; fungicide, bactericide,
                                   and nematocide
  DDT (p,p'-DDT)                 Production; nonsystemic insecticide
  1,2-Dibromo-3-chloropropane    Production; pesticide, nematocide,
                                   and soil fumigant
  para-Dichlorobenzene           Production, pesticide
  Dichlorvos                     Production; insecticide and miticide
  Heptachlor                     Production, termite control
  Hexachlorobenzene              Production, in chlorinated pesticides
                                   and fungicides; dye manufacture and
                                   synthesis of organic chemicals and
                                   rubber, plasticizer for polyvinyl
                                   chloride; wood preservative, by-
                                   product of the production of a
                                   number of chlorinated solvents
  Hexachlorocyclohexanes         Production; woodworkers; farm workers
    (most common form is
    Lindane)
  Mirex                          Production; fire-retardant additive,
                                   insecticide, workers at hazardous
                                   waste sites
  Nitrofen                       Production, herbicide
  Sodium ortho-phenylphenate     Production; fungicide, chemical
                                   intermediate
  Toxaphene (polychloronated     Production; insecticide
    camphenes)
Others
  Butylated hydroxyanisole       Production, food and pharmaceutical
    (BHA)                          industries
  Catechol                       Production; insecticide and
                                   pharmaceutical production,
                                   tanneries
  Diglycidyl resorcinol ether    Production; liquid spray epoxy resin
                                   in electrical, tooling, adhesive,
                                   and laminating applications,
                                   production of epoxy resins and
                                   rubber, aerospace industry
  1,4-Dioxane                    Production, chlorinated solvents,
                                   textile processing, mixed with
                                   pesticides
  Hydrazine                      Production, manufacture of
                                   agricultural chemicals and chemical
                                   blowing agents, water treatment;
                                   spandex fibers; rocket fuel,
                                   oxygen scavenger in water boilers
                                   and heating systems, scavenger for
                                   gases; plating metals on glass and
                                   plastics, solder fluxes;
                                   photographic developers; reactant
                                   in fuel cells in the military,
                                   reducing agent in electrode-less
                                   nickel plating, chain extender in
                                   urethane; textile dyes, explosives
  Nitrilotriacetic acid and      Production; textiles, electroplaters,
    its salts                      tanners
  Polychlorophenols and their    Herbicide production, wood, textile
    sodium salts (mixed            and leather manufacturing
    exposure)
  Potassium bromate              Production, bakeries
  Thiourea                       Production, photoprocessing, dyes,
                                   rubber industry
  Welding fumes                  Metal fabricating industry

                                  IARC Monograph         Human
Substance or mixture             volume (year) (b)   evidence (c)

Respirable dusts and fibers
  Glass wool                      Vol. 81 (2002a)     Inadequate
  Palygorskite (long fibers       Vol. 68 (1997b)     Inadequate
    > 5 [micro]m)
  Refractory ceramic fibers       Vol. 81 (2002a)     Inadequate
  Rock wool                       Vol. 81 (2002a)     Inadequate
  Slag wool fireproofing          Vol. 81 (2002a)     Inadequate
  Special-purpose glass fibers    Vol. 81 (2002a)    Not available
    such as E-glass and "475"
    glass fibers
Metals and metal compounds
  Antimony trioxide               Vol. 47(1989c)      Inadequate
  Cobalt and cobalt compounds     Vol. 52 (1991a)     Inadequate
  Lead and inorganic lead         Suppl. 7 (1987)     Inadequate
    compounds
  Methyl mercury compounds        Vol. 58 (1993a)     Inadequate
  Nickel: metallic and alloys     Vol. 49 (1990a)     Inadequate
Wood and fossil fuels and
    their by-products
  Benzofuran                      Vol. 63 (1995a)    Not available
  Bitumens, extracts of steam-    Suppl. 7 (1987)     Inadequate
    refined and air-refined
  Carbon black                    Vol. 65 (1996)      Inadequate
  Diesel fuel, marine             Vol. 45 (1989b)     Inadequate
  Fuel oils, residual (heavy)     Vol. 45 (1989b)     Inadequate
  Gasoline                        Vol. 45 (1989b)     Inadequate
  Gasoline engine exhaust         Vol. 46(1989a)      Inadequate
  Naphthalene                     Vol. 82 (2002b)     Inadequate
Polyaromatic hydrocarbons
  Benzo[b]fluoranthene            Vol. 32 (1983b)    Not available
  Benzo[j]fluoranthene            Vol. 32 (1983b)    Not available
  Benzo[k]fluoranthene            Vol. 32 (1983b)    Not available
  Dibenz[a,h]acridine             Vol. 32 (1983b)    Not available
  Dibenz[a,j]acridine             Vol. 32 (1983b)    Not available
  Dibenzo[a,e]pyrene              Vol. 32 (1983b)    Not available
  Dibenzo[a,h]pyrene              Vol. 32 (1983b)    Not available
  Dibenzo[a,i]pyrene              Vol. 32 (1983b)    Not available
  Dibenzo[a,4pyrene               Vol. 32 (1983b)    Not available
Monomers
  Acrylonitrile                   Vol. 71 (1999a)     Inadequate
  Chloroprene                     Vol. 71 (1999a)     Inadequate
  Ethyl acrylate                  Vol. 39 (1986a)    Not available
  Isoprene                        Vol. 71 (1999a)    Not available
  Styrene                         Vol. 82 (2002b)       Limited
  Toluene diisocyanates           Vol. 71 (1999a)     Inadequate
  Urethane                        Vol. 7 (1974a)     Not available
  Vinyl acetate                   Vol. 63 (1995a)    Not available
Intermediates in plastics and
    rubber manufacturing
  Acetaldehyde                    Vol. 71 (1999a)     Inadequate
  Acetamide                       Vol. 71 (1999a)    Not available
  2,4-Diaminotoluene              Vol. 16 (1978)     Not available
  1,2-Epoxybutane                 Vol. 71 (1999a)    Not available
  Ethylbenzene                    Vol. 77 (2000b)     Inadequate
  Ethylene thiourea               Vol. 79 (2001b)     Inadequate
  Phenyl glycidyl ether           Vol. 71 (1999a)    Not available
  Propylene oxide                 Vol. 60 (1994)      Inadequate
Chlorinated hydrocarbons
  Carbon tetrachloride            Vol. 71 (1999a)     Inadequate
  Chlorinated paraffin of         Vol. 48 (1990b)    Not available
    average carbon-chain
    length C12
  Chloroform                      Vol. 73 (1999b)     Inadequate
  1,2-Dichloroethane              Vol. 71 (1999a)     Inadequate
  Dichloromethane                 Vol. 71 (1999a)     Inadequate
  Hexachloroethane                Vol. 73 (1999b)     Inadequate
Aromatic amine dyes
  Auramine (technical grade)      Suppl. 7 (1987)     Inadequate
  Benzyl violet 4B                Vol. 16 (1978)     Not available
  CI Basic Red 9                  Vol. 57 (1993b)     Inadequate
  2,4-Diaminoanisole              Vol. 79 (2001b)    Not available
  3,3'-Dimethylbenzidine           Vol. 1 (1972)     Not available
    (o-tolidine)
  2,6-Dimethylaniline             Vol. 57 (1993b)    Not available
    (2,6-xylidine)
  3,3'-Dichlorobenzidine          Vol. 29 (1982b)     Inadequate
  4,4'-Diaminodiphenyl ether      Vol. 29 (1982b)    Not available
  Disperse Blue 1                 Vol. 48 (1990b)    Not available
  HC Blue No. 1                   Vol. 57 (1993b)    Not available
  4,4'-Methylenedianiline         Vol. 39 (1986a)    Not available
  Magenta containing              Vol. 57 (1993b)    Not available
    CI Basic Red 9
Azo dyes
  ortho-Aminoazotoluene            Vol. 8 (1975)     Not available
  para-Aminoazobenzene            Suppl. 7 (1987)    Not available
  CI Acid Red 114                 Vol. 57 (1993b)    Not available
  CI Direct Blue 15               Vol. 57 (1993b)    Not available
  Citrus Bed No. 2                 Vol. 8 (1975)     Not available
  para-Dlmethylaminoazobenzene     Vol. 8 (1975)     Not available
  Oil orange SS                    Vol. 8 (1975)     Not available
  Ponceau 3R                       Vol. 8 (1975)     Not available
  Ponceau MX                       Vol. 8 (1975)     Not available
  Trypan blue                      Vol. 8 (1975)     Not available
Intermediates for the
    manufacture of dyes
  para-Cresidine                  Vol. 27 (1982a)    Not available
  3,3'-Dimethoxybenzidine         Suppl. 7 (1987)     Inadequate
    (ortho-dianisidine)
  2-Methyl-1-nitro                Vol. 27 (1982a)    Not available
    anthraquinone (of
    uncertain purity/impurity)
  4,4'-Methylene bis (2-          Suppl. 7(1987)      Inadequate
    methylaniline)
  2-Nitroanisole                  Vol. 65 (1996)     Not available
  4,4'-Thiodianiline              Vol. 27 (1982a)    Not available
Nitro compounds
  2,4-Dinitrotoluene              Vol. 65 (1996)      Inadequate
  2,6-Dinitrotoluene              Vol. 65 (1996)      Inadequate
  Nitrobenzene                    Vol. 65 (1996)     Not available
  2-Nitrofluorene                 Vol. 46 (1989a)    Not available
  2-Nitropropane                  Vol. 71 (1999a)    Not available
  1-Nitropyrene                   Vol. 46 (1989a)    Not available
  4-Nitropyrene                   Vol. 46 (1989a)    Not available
  Tetranitromethane               Vol. 65 (1996)     Not available
Pesticides
  Aramite                         Vol. 5 (1974b)     Not available
  Chlordane                       Vol. 79 (2001b)     Inadequate
  Chlordecone                     Vol. 20 (1979a)    Not available
  Chlorophenoxy herbicides        Suppl. 7 (1987)       Limited
  Chlorothalonil                  Vol. 73 (1999b)    Not available
  DDT (p,p'-DDT)                  Vol. 53 (1991b)     Inadequate
  1,2-Dibromo-3-chloropropane     Vol. 71 (1999a)     Inadequate
  para-Dichlorobenzene            Vol. 73 (1999b)     Inadequate
  Dichlorvos                      Vol. 53 (1991b)     Inadequate
  Heptachlor                      Vol. 79 (2001b)     Inadequate
  Hexachlorobenzene               Vol. 79 (2001b)     Inadequate
  Hexachlorocyclohexanes          Suppl.7 (1987)      Inadequate
    (most common form is
    Lindane)
  Mirex                           Vol. 20 (1979a)    Not available
  Nitrofen                        Vol. 30 (1983a)    Not available
  Sodium ortho-phenylphenate      Vol. 73 (1999b)    Not available
  Toxaphene (polychloronated      Vol. 79 (2001b)     Inadequate
    camphenes)
Others
  Butylated hydroxyanisole        Vol. 40 (1986b)    Not available
    (BHA)
  Catechol                        Vol. 71 (1999a)    Not available
  Diglycidyl resorcinol ether     Vol. 71 (1999a)    Not available
  1,4-Dioxane                     Vol. 71 (1999a)     Inadequate
  Hydrazine                       Vol. 71 (1999a)     Inadequate
  Nitrilotriacetic acid and       Vol. 73 (1999b)    Not available
    its salts
  Polychlorophenols and their     Vol. 71 (1999a)       Limited
    sodium salts (mixed
    exposure)
  Potassium bromate               Vol. 73 (1999b)    Not available
  Thiourea                        Vol. 79 (2001b)    Not available
  Welding fumes                   Vol. 49 (1990a)       Limited

                                    Animal
Substance or mixture             evidence (c)

Respirable dusts and fibers
  Glass wool                      Sufficient
  Palygorskite (long fibers       Sufficient
    > 5 [micro]m)
  Refractory ceramic fibers       Sufficient
  Rock wool                        Limited
  Slag wool fireproofing           Limited
  Special-purpose glass fibers    Sufficient
    such as E-glass and "475"
    glass fibers
Metals and metal compounds
  Antimony trioxide               Sufficient
  Cobalt and cobalt compounds     Sufficient
  Lead and inorganic lead         Sufficient
    compounds
  Methyl mercury compounds        Sufficient
  Nickel: metallic and alloys     Sufficient
Wood and fossil fuels and
    their by-products
  Benzofuran                      Sufficient
  Bitumens, extracts of steam-    Sufficient
    refined and air-refined
  Carbon black                    Sufficient
  Diesel fuel, marine              Limited
  Fuel oils, residual (heavy)     Sufficient
  Gasoline                         Limited
  Gasoline engine exhaust          Limited
  Naphthalene                     Sufficient
Polyaromatic hydrocarbons
  Benzo[b]fluoranthene            Sufficient
  Benzo[j]fluoranthene            Sufficient
  Benzo[k]fluoranthene            Sufficient
  Dibenz[a,h]acridine             Sufficient
  Dibenz[a,j]acridine             Sufficient
  Dibenzo[a,e]pyrene              Sufficient
  Dibenzo[a,h]pyrene              Sufficient
  Dibenzo[a,i]pyrene              Sufficient
  Dibenzo[a,4pyrene               Sufficient
Monomers
  Acrylonitrile                   Sufficient
  Chloroprene                     Sufficient
  Ethyl acrylate                  Sufficient
  Isoprene                        Sufficient
  Styrene                          Limited
  Toluene diisocyanates           Sufficient
  Urethane                        Sufficient
  Vinyl acetate                    Limited
Intermediates in plastics and
    rubber manufacturing
  Acetaldehyde                    Sufficient
  Acetamide                       Sufficient
  2,4-Diaminotoluene              Sufficient
  1,2-Epoxybutane                  Limited
  Ethylbenzene                    Sufficient
  Ethylene thiourea               Sufficient
  Phenyl glycidyl ether           Sufficient
  Propylene oxide                 Sufficient
Chlorinated hydrocarbons
  Carbon tetrachloride            Sufficient
  Chlorinated paraffin of         Sufficient
    average carbon-chain
    length C12
  Chloroform                      Sufficient
  1,2-Dichloroethane              Sufficient
  Dichloromethane                 Sufficient
  Hexachloroethane                Sufficient
Aromatic amine dyes
  Auramine (technical grade)      Sufficient
  Benzyl violet 4B                Sufficient
  CI Basic Red 9                  Sufficient
  2,4-Diaminoanisole              Sufficient
  3,3'-Dimethylbenzidine          Sufficient
    (o-tolidine)
  2,6-Dimethylaniline             Sufficient
    (2,6-xylidine)
  3,3'-Dichlorobenzidine          Sufficient
  4,4'-Diaminodiphenyl ether      Sufficient
  Disperse Blue 1                 Sufficient
  HC Blue No. 1                   Sufficient
  4,4'-Methylenedianiline         Sufficient
  Magenta containing              Sufficient
    CI Basic Red 9
Azo dyes
  ortho-Aminoazotoluene           Sufficient
  para-Aminoazobenzene            Sufficient
  CI Acid Red 114                 Sufficient
  CI Direct Blue 15               Sufficient
  Citrus Bed No. 2                Sufficient
  para-Dlmethylaminoazobenzene    Sufficient
  Oil orange SS                   Sufficient
  Ponceau 3R                      Sufficient
  Ponceau MX                      Sufficient
  Trypan blue                     Sufficient
Intermediates for the
    manufacture of dyes
  para-Cresidine                  Sufficient
  3,3'-Dimethoxybenzidine         Sufficient
    (ortho-dianisidine)
  2-Methyl-1-nitro                Sufficient
    anthraquinone (of
    uncertain purity/impurity)
  4,4'-Methylene bis (2-          Sufficient
    methylaniline)
  2-Nitroanisole                  Sufficient
  4,4'-Thiodianiline              Sufficient
Nitro compounds
  2,4-Dinitrotoluene              Sufficient
  2,6-Dinitrotoluene              Sufficient
  Nitrobenzene                    Sufficient
  2-Nitrofluorene                 Sufficient
  2-Nitropropane                  Sufficient
  1-Nitropyrene                   Sufficient
  4-Nitropyrene                   Sufficient
  Tetranitromethane               Sufficient
Pesticides
  Aramite                         Sufficient
  Chlordane                       Sufficient
  Chlordecone                     Sufficient
  Chlorophenoxy herbicides        Inadequate
  Chlorothalonil                  Sufficient
  DDT (p,p'-DDT)                  Sufficient
  1,2-Dibromo-3-chloropropane     Sufficient
  para-Dichlorobenzene            Sufficient
  Dichlorvos                      Sufficient
  Heptachlor                      Sufficient
  Hexachlorobenzene               Sufficient
  Hexachlorocyclohexanes          Sufficient
    (most common form is
    Lindane)
  Mirex                           Sufficient
  Nitrofen                        Sufficient
  Sodium ortho-phenylphenate      Sufficient
  Toxaphene (polychloronated      Sufficient
    camphenes)
Others
  Butylated hydroxyanisole        Sufficient
    (BHA)
  Catechol                        Sufficient
  Diglycidyl resorcinol ether     Sufficient
  1,4-Dioxane                     Sufficient
  Hydrazine                       Sufficient
  Nitrilotriacetic acid and       Sufficient
    its salts
  Polychlorophenols and their     Inadequate
    sodium salts (mixed
    exposure)
  Potassium bromate               Sufficient
  Thiourea                        Sufficient
  Welding fumes                   Inadequate

TDI, toluene diisocyanate.

(a) Not necessarily an exhaustive list of occupations/industries
in which this agent is found; not all workers in these occupations/
industries are exposed. The term "production" is used to indicate
that this substance is man-made and that workers may be exposed in
the production process. (b) Most recent IARC evaluation; for those
referenced as Supplement 7 (ARC 1987), it is possible that the 1987
review was quite perfunctory and that the essential evidence was
cumulated at an earlier date. (c) As judged by the IARC working
group; we added the notation "not available" to signify those
substances for which there was no epidemiologic evidence at all.

Table 6. 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

Aluminum production                    Pitch volatiles, aromatic
                                         amines
Auramine manufacture                   2-Naphthylamine; auramine;
                                         other chemicals, pigments
Boot and shoe manufacture and repair   Leather dust; benzene and other
                                         solvents
Carpentry and joinery                  Wood dust
Coal gasification                      Coal tar, coal-tar fumes; PAHs
Coke production                        Coal-tar fumes
Dry cleaning                           Solvents and chemicals used in
                                         "spotting"
Furniture and cabinet making           Wood dust
Hairdressers and barbers               Dyes (aromatic amines, amino-
                                         phenols with hydrogen
                                         peroxide), solvents;
                                         propellants, aerosols
Hematite mining, underground, with     Radon daughters; silica
  radon exposure
Iron and steel founding                PAHs; silica, metal fumes,
                                         formaldehyde
Isopropanol manufacture, strong-acid   Diisopropyl sulfate; isopropyl
  process                                oils, sulfuric acid
Magenta manufacture                    Magenta; ortho-toluidine;
                                         4,4'-methylene
                                         bis(2-methylaniline);
                                         ortho-nitrotoluene
Painters
Petroleum refining                     PAHs
Printing processes                     Solvents, inks
Production of art glass, glass         Lead; arsenic, antimony oxides;
  containers, and pressed ware           silica; asbestos, other metal
                                         oxides, PAHs
Rubber industry                        Aromatic amines; solvents
Textile manufacturing industry         Textile dust in manufacturing
                                         process, dyes and solvents in
                                         dyeing and printing
                                         operations

                                        IARC Monograph
Occupation or industry                 volume (year) (a)   Group

Aluminum production                     Suppl. 7 (1987)      1
Auramine manufacture                    Suppl. 7 (1987)      1
Boot and shoe manufacture and repair    Suppl. 7 (1987)      1
Carpentry and joinery                   Suppl. 7 (1987)     2B
Coal gasification                       Vol. 34 (1984)       1
Coke production                         Suppl. 7 (1987)      1
Dry cleaning                            Vol. 63 (1995a)     2B
Furniture and cabinet making            Suppl. 7 (1987)      1
Hairdressers and barbers                Vol. 57 (1993b)     2A
Hematite mining, underground, with      Suppl. 7 (1987)      1
  radon exposure
Iron and steel founding                 Suppl. 7 (1987)      1
Isopropanol manufacture, strong-acid    Suppl. 7 (1987)      1
  process
Magenta manufacture                     Vol. 57 (1993b)      1
Painters                                Vol. 47 (1989c)      1
Petroleum refining                      Vol. 45 (1989b)     2A
Printing processes                      Vol. 65 (1996)      2B
Production of art glass, glass          Vol. 58 (1993a)     2A
  containers, and pressed ware
Rubber industry                         Suppl. 7 (1987)      1
Textile manufacturing industry          Vol. 48 (1990b)     2B

Occupation or industry                             Site(s)

Aluminum production                    Lung, (b) bladder (b)
Auramine manufacture                   Bladder (b)
Boot and shoe manufacture and repair   Leukemia, (b) nose, (b)
                                         paranasal sinuses, (b)
                                         bladder (c)
Carpentry and joinery
Coal gasification                      Skin (including scrotum) (b)
                                         bladder, (b) lung (b)
Coke production                        Skin (scrotum), (b) lung, (b)
                                         bladder, (c) kidney (c)
Dry cleaning
Furniture and cabinet making           Nose and sinonasal cavities (b)
Hairdressers and barbers               Bladder, (c) lung, (c) non-
                                         Hodgkin lymphoma, (c)
                                         ovary (c)
Hematite mining, underground, with     Lung (b)
  radon exposure
Iron and steel founding                Lung (b)
Isopropanol manufacture, strong-acid   Paranasal sinuses, (b) larynx,
  process                                (b) lung (c)
Magenta manufacture                    Bladder (b)
Painters                               Lung, (b) bladder, (c)
                                         stomach (c)
Petroleum refining                     Bladder, (c) brain, (c)
                                         leukemia (c)
Printing processes
Production of art glass, glass         Lung (c)
  containers, and pressed ware
Rubber industry                        Bladder, (b) stomach, (c)
                                         larynx, (c) leukemia, (c)
                                         lung (c)
Textile manufacturing industry

(a) Most recent ARC evaluation; for those referenced as Supplement 7
(IARC 1987), it is possible that the 1987 review was quite perfunctory
and that the essential evidence was cumulated at an earlier date.
(b) We judged that the evidence for an association with this site was
strong. (c) We judged that the evidence was suggestive.

Table 7. Definite or probable occupational carcinogens and
carcinogenic circumstances, by site.

                      Strength of        High-risk substance or
Site                  evidence (a)            circumstance

Pharynx and           Suggestive     Mustard gas; formaldehyde
  nasopharynx
Nasal cavities and    Strong         Boot and shoe manufacture and
  paranasal sinuses                    repair; furniture and cabinet
                                       making, isopropanol
                                       manufacture, strong acid
                                       process; selected nickel
                                       compounds, including
                                       combinations of nickel oxides
                                       and sulfides in the nickel-
                                       refining industry; wood dust
                      Suggestive     Chromium compounds, hexavalent;
                                       formaldehyde; mineral oils,
                                       untreated and mildly treated

Esophagus             Suggestive     Soots; tetrachloroethylene
Stomach               Suggestive     Painters, rubber industry
Gastrointestinal      Suggestive     Asbestos
  tract
Liver and biliary     Strong         Aflatoxin, ionizing radiation
  tract               Suggestive     Polychlorinated biphenyls;
                                       trichloroethylene
Liver                 Strong         Vinyl chloride
  (angiosarcoma)      Suggestive     Arsenic and arsenic compounds
Liver                 Suggestive     Vinyl chloride
  (hepatocellular)
Pancreas              Suggestive     Acrylamide
Larynx                Strong         Isopropanol manufacture, strong
                                       acid process; inorganic acid
                                       mists containing sulfuric acid,
                                       mustard gas
                      Suggestive     Asbestos, rubber industry
Lung                  Strong         Aluminum production; arsenic and
                                       arsenic compounds, asbestos,
                                       beryllium, cadmium and cadmium
                                       compounds, chromium compounds,
                                       hexavalent; coal gasification;
                                       coke production, hematite
                                       mining, underground, with radon
                                       exposure, involuntary (passive)
                                       smoking; ionizing radiation;
                                       iron and steel founding,
                                       selected nickel compounds,
                                       including combinations of
                                       nickel oxides and sulfides in
                                       the nickel refining industry,
                                       painters, silica, crystalline,
                                       soots, talc containing
                                       asbestiform fibers
                      Suggestive     Benz[a]anthrace ne; benzo[a]-
                                       pyrene; a-chlorinated toluenes;
                                       coal tars and pitches; dibenz-
                                       [a,h]anthracene; diesel engine
                                       exhaust, epichlorohydrin,
                                       hairdressers and barbers,
                                       inorganic acid mists containing
                                       sulfuric acid; isopropanol
                                       manufacture (strong acid
                                       process); mineral oils
                                       (untreated and mildly treated);
                                       nonarsenical insecticides;
                                       mustard gas, production of art
                                       glass, glass containers, and
                                       pressed ware, rubber industry,
                                       TCDD
Lung (oat cell)       Strong         Bis(chloromethyl) ether and
                                       chloromethyl methyl ether
                                       (technical grade)
Bone                  Strong         Ionizing radiation
Melanoma              Strong         Solar radiation
                      Suggestive     Ultraviolet radiation (A, B and
                                       C) from artificial sources
Skin                  Strong         Arsenic and arsenic compounds,
                                       Coal tars and pitches; coal
                                       gasification; coke production;
                                       dibenz[a,h]anthracene; mineral
                                       oils, untreated and mildly
                                       treated, shale oils or shale-
                                       derived lubricants, solar
                                       radiation, soots
                      Suggestive     Benz[a]anthracene;
                                       benzo[a]pyrene; creosotes
Mesothelioma          Strong         Asbestos; erionite; talc
                                       containing asbestiform fibers
CNS                   Suggestive     Epichlorohydrin
Sarcoma               Suggestive     TCDD
Cervix                Suggestive     Tetrachloroethylene
Ovary                 Suggestive     Hairdressers and barbers
Kidney                Suggestive     Coke production
Kidney (renal cell)   Suggestive     Trichlorethylene
Bladder               Strong         Aluminum production, 4-
                                       aminobiphenyl; auramine
                                       manufacture; benzidine; coal
                                       gasification, magenta
                                       manufacture, 2-naphthylamine,
                                       rubber industry
                      Suggestive     Benz[a]anthracene; benzidine-
                                       based dyes, benzo[a]pyrene;
                                       boot and shoe manufacture and
                                       repair; 4-chloro-ortho-
                                       toluidine, coal tars and
                                       pitches; coke production;
                                       dibenz[a,h]anthracene; diesel
                                       engine exhaust, hairdressers
                                       and barbers, 4,4'-methylene
                                       bis(2-chloroaniline), mineral
                                       oils, untreated and mildly
                                       treated, ortho-toluidine;
                                       painters; petroleum refining
Brain                 Suggestive     Nonarsenical insecticides,
                                       petroleum refining
Thyroid               Strong         Ionizing radiation
Non-Hodgkin           Suggestive     Hairdressers and barbers;
  lymphoma                             nonarsenical insecticides;
                                       TCDD; tetrachloroethylene,
                                       trichloroethylene
Lympho-hema           Suggestive     1,3-Butadiene
  topoietic system
Multiple myeloma      Suggestive     Nonarsenical insecticides
Leukemia              Strong         Benzene; boot and shoe
                                       manufacture and repair;
                                       ethylene oxide, ionizing
                                       radiation
                      Suggestive     Formaldehyde; nonarsenical
                                       insecticides, petroleum
                                       refining; rubber industry
Other sites           Suggestive     Ionizing radiation'
All sites combined    Strong         TCDD (c)

CNS, central nervous system; TCDD, 2,3,7,8-tetrachlorodibenzo-
para-dioxin.

(a) Our judgment of strength of evidence regarding each site.
(b) There is suggestive evidence of an effect of ionizing radiation
on several sites in addition to those shown here. (c) The evidence
for an association with TCDD only becomes strong when data are
combined for all cancer sites.

Table 8. Evolution in knowledge regarding current
(2003) IARC occupational carcinogens.

                       Earlier evaluation

Current rating   Past rating   IARC 1987   WHO 1964

1 (n = 28)            1           19          13
                     2A            4           4
                     2B            1           4
                      3            0          NA
                   Unrated         4          11
                    Total         28          28
2A (n = 27)           1            0           0
                     2A           16           0
                     2B            6           0
                      3            2          NA
                   Unrated         3          27
                    Total         27          27
2B (n = 113)          1            0           1
                     2A            2           5
                     2B           63           5
                      3            9          NA
                   Unrated        39         107
                    Total        113         113

NA, not applicable.

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Jack Siemiatycki, (1,2) Lesley Richardson, (3) Kurt Straif, (3) Benoit Latreille, (4) Ramzan Lakhani, (4) Sally Campbell, (4) Marie-Claude Rousseau, (1) and Paolo Boffetta (3,5)

(1) Departement de Medecine sociale et preventive, Universite de Montreal, Montreal, Quebec, Canada; (2) Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada; (3) International Agency for Research on Cancer, Lyon, France; (4) INRS-Institut Armand-Frappier, Laval, Quebec, Canada; (5) Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany

Address correspondence to J. Siemiatycki, Departement de Medecine sociale et preventive, Universite de Montreal, P.O. Box 6128, stn Centre-Ville, Montreal, Quebec, Canada, H3C 3J7. Telephone: [phone]. Fax: [phone]. E-mail: j.siemiatycki@ umontreal.ca

This work was in part supported by funds from the Centre de recherche du CHUM and from the Canada Research Chair Program.

The authors declare they have no competing financial interests.

Received 19 February 2004; accepted 14 July 2004.