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Carcinogens: Different classifications

Three main lists of internationally recognized carcinogens exist: those of IARC, of the ACGIH and of the European Union (CLP). It becomes thus difficult to find one’s way as a novice!

In particular when there are disparities as regards their classification as well as the list of chemicals concerned. The different classifications and their definitions are grouped below, so as to bring more light and better understanding regarding these differences.

IARC Classification

The International Agency for Research on Cancer (IARC or CIRC in French) distinguishes four main groups or physical factors on the basis of existing scientific data to assess their carcinogenic potential.

GROUP 1the agent may be a carcinogenic mixture for humans (proven carcinogen or certainly carcinogenic). The exposure circumstance entails exposures that are carcinogenic to humans. This category is only used when sufficient indications of carcinogenicity for humans are available. Beginning of August 2012, 108 agents are classified in Group 1 of IARC. This group is divided in sub-groups: agents and groups of agents, complex mixtures, occupational exposures and others.

GROUP 2A: The mentioned agents are probably carcinogenic for human beings. The classification of an agent in this category is recommended if there is no formal evidence of carcinogenicity in humans, but corroborating indicators of its carcinogenicity for humans and sufficient evidence of carcinogenicity in experimental animals. Beginning of August 2012, 64 agents and group of agents are included in this list.

GROUP 2B: 272 agents appear on this list of agents probably carcinogenic to humans. There is limited evidence of carcinogenicity in humans and evidence for animals, or insufficient evidence for human beings but sufficient evidence of carcinogenicity in experimental animals (possible carcinogens).

GROUP 3: 508 agents appear on this list and are not classifiable as to their carcinogenicity to humans. (Insufficient evidence for human beings and insufficient or limited for animals).

GROUP 4: to indicate agents which are probably not carcinogenic for human beings. (Evidence suggesting lack of carcinogenicity in humans and in experimental animals). Only one agent is thus classified: Caprolactam.

Classification of the ACGIH

The American Conference of Governmental Industrial Hygienists (ACGIH) distinguishes five categories of chemicals or carcinogenic agents:

  • GROUP A1: confirmed human carcinogens (group 1 of IARC and category 1A of the European Union).
  • GROUP A2: suspected human carcinogens (group 2A of IARC and category 1B of European Union).
  • GROUP A3: confirmed animal carcinogens with unknown relevance to humans (group 2B of IARC and category 2 of the European Union).
  • GROUP A4: regroups agents non-classifiable as to their carcinogenicity to humans (group 3 of IARC).
  • GROUP A5: regroups agents suspected not to be carcinogenic to humans (group 4 of IARC).

Classification of the European Union (CLP)

Category 1A: includes substances whose potential carcinogenicity for humans is known; classification in this category is primarily based on human data.

Category 1B: includes substances whose carcinogenic potential to humans is presumed, classification in this category is primarily based on animal data.

In summary, classification in category 1A and 1B is based on evidential weight of data which may be derived from studies on human beings with a causal link between human exposure to a substance and cancer occurrence (category 1A) and animal experiments for which there is sufficient evidence to demonstrate animal carcinogenicity (presumed human carcinogen) (category 1B)

Category 2: includes substances suspected of being carcinogenic to humans. This classification is done on the basis of evidences obtained from human and/or animal studies not sufficiently convincing to place in category 1A or 1B.

The differences

It may therefore be estimated that chemicals classified in group 1 of IARC, A1 of the ACGIH and in category 1A of the European Union are human categories.

It is important to point out that substantial differences exist, comparing the three lists of carcinogens with each other. Each of these differences cannot be detailed here; we will simply cite the most used substances.

If we take as reference the list of human carcinogens for IARC, we can try to see major differences and similarities that exist with that of ACGIH and of European Union.

Are classified as human carcinogens:

  • Asbestos,
  • Aminobiphenyl,
  • Arsenic and its compounds,
  • Benzene,
  • Benzidine,
  • Chloroethylene,
  • Beryllium and its compounds,
  • The bis(chloromethyl)ether and the chloromethylether (technical grade),
  • Chromium VI and its compounds with the exception of barium chromate classified in group 1B in the European Union,
  • Coal tar,
  • Methylenebis(2-chloroaniline) (it is worth mentioning that it is classified as probable carcinogen A2 of the ACGIH),
  • Naphtylamine.

As we see, there are particularly major differences between the chemicals included in the list of the ACGIH and those of the IARC and the European Union. The European Union and the IARC lists are closer, but it is important to bear in mind that the chemicals classified in group 1 of the IARC can just as well be listed in categories 1A or 1B of the CLP.

Some examples to remember

Many chemicals are classified as carcinogens only by the IARC :

  • Azathiopirine,
  • Chlornaphazine,
  • Myleran,
  • Chlorambucil,
  • Semustine,
  • Cyclosporine,
  • Oral contraceptives,
  • Cyclophosphamide,
  • Diethylsilbestrol,
  • Etoposide combined with cisplastine and bleomycine,
  • Yperite,
  • Helicobacter pylori infections,
  • Radioactive iodine,
  • Melphalan,
  • Methoxy-8-psoralen,
  • MOPP,
  • Neutrons,
  • N-nitrosonornicotine,
  • Estrogen therapy,
  • Phosphorous 32 (in the form of phosphate),
  • Plutonium 239 and 240,
  • Radioelements emitting alpha and beta particles,
  • Radium 224,226,228,222,
  • X and gamma rays,
  • Tamoxifene,
  • TCDD,
  • Thiotepa,
  • Thorium 232
  • And many viruses.

We will not mention here lists of mixtures and detailed occupational carcinogen exposures in the IARC list.

Other differences give rise to questions

Carcinogenic chemical IARC ACGIH CLP
Formaldehyde Group 1 Group A2 Cat. 2
Gallium arsenide Group 1 Group A3
Ethylene oxyde Group 1 Group A2 Cat. 1B
o-Toluidine Group 1 Group A3 Cat. 1B

These classification differences can no doubt be explained by the limits of animal testing and other differences in interpretation of human and experimental data but must question ourselves.
For greater safety and security, it seems logical to consider that the classification the most restrictive must be respected but this requires a clear understanding of the various lists.

These lists are reviewed in PROMETRA and meet the following classification:

  • 1001: list of carcinogens or suspected according to the IARC
  • 1020: list of carcinogens or suspected according to the ACGIH
  • 1030: list of carcinogens or suspected according to the European Union (CLP)

Centre International de Recherche sur le Cancer
American Conference of Industrial Hygienists
Classification Labelling and Packaging of substances and mixtures, (CE) n°1272/2008

Danielle Henny, Occupational Health Physician