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A review of human carcinogens - Part F: chemical agents and related occupations.

Baan R; Grosse Y; Straif K; Secretan B; El Ghissassi F; Bouvard V; Benbrahim-Tallaa L; Guha N; Freeman C; Galichet L; Cogliano V; WHO International Agency for Research on Cancer Monograph Working Group
Lancet Oncol 2009 Dec; 10(12):1143-1144
In October, 2009, 23 scientists from six countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of several chemical and occupational exposure circumstances previously classified as "carcinogenic to humans" (Group 1) and to identify additional tumour sites and mechanisms of carcinogenesis. These assessments will be published as the sixth and last part of Volume 100 of the IARC Monographs. Four aromatic amines and two related industrial processes were reaffirmed as Group-1 carcinogens based on sufficient evidence that they cause urinary bladder cancer in humans. The Group-1 classification of dyes metabolised to benzidine and of 4,4'-methylenebis(2-chloroaniline) was based on sufficient evidence in animal models and strong mechanistic evidence. Exposure to polycyclic aromatic hydrocarbons (PAHs) causes cancers of the skin and lung in humans. Various PAH-related industries and PAH-containing complex mixtures were confirmed as Group-1 carcinogens. Although there are no epidemiological studies of benzo[a]pyrene, carcinogenicity in many animal species and strong mechanistic evidence justified its classification in Group 1. The carcinogenicity to humans of other chemicals and exposure scenarios was reaffirmed. For ethylene oxide, the epidemiological evidence was limited, but there is sufficient evidence for its carcinogenicity in rodents. Additionally, ethylene oxide is genotoxic and mutagenic in many in-vitro tests and in-vivo studies in animals, and its cytogenetic effects in lymphocytes of exposed workers provided strong support for its classification in Group 1. Workers in the rubber-manufacturing industry have an increased risk for leukaemia, lymphoma, and cancers of the urinary bladder, lung, and stomach. Due to the diversity and complexity of the exposures in this industry, it is difficult to identify causative agents, but there is strong evidence of genotoxic effects in these workers. The Working Group reviewed more than 100 epidemiological studies of benzene and confirmed its carcinogenicity, with sufficient evidence for acute non-lymphocytic leukaemia. (ANLL), and limited evidence for acute lymphocytic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL). The Working Group also found limited evidence of an association between maternal exposure to painting "before and during pregnancy" and an increased risk of childhood leukaemia in the off spring. Dioxin (2,3,7,8-tetrachlorodibenzopara-dioxin, TCDD) was classified in Group 1 in 1997, based on limited evidence of carcinogenicity in humans, sufficient evidence in rodents, and strong evidence in humans and animals for a mechanism via initial binding to the aryl hydrocarbon receptor (AhR), which leads to changes in gene expression, cell replication, and apoptosis. There is now sufficient epidemiological evidence for all cancers combined, making TCDD the first agent classified initially in Group 1 based on sufficient animal data and mechanisms, to be later confirmed by increased cancer incidence in humans. This highlights the ability of mechanistic information to provide robust evidence of carcinogenicity. Like TCDD, 2,3,4,7,8-pentachlorodibenzofuran and 3,3',4,4',5-pentachlorobiphenyl (PCB-126) are complete carcinogens in experimental animals, and there is extensive evidence that they act through the same AhR-mediated mechanism. The Working Group classified these two chemicals in Group 1. The Working Group unanimously reaffirmed the classification of formaldehyde in Group 1, based on sufficient evidence in humans of nasopharyngeal cancer. A possible association with leukaemia was previously considered "strong but not sufficient", because of the lack of a plausible mechanism. The epidemiological evidence has become stronger: a recent study found that embalming was significantly associated with an increased risk for myeloid leukaemia, with significant trends for cumulative years of embalming (ptrend=0·020) and for increasing peak formaldehyde exposure (ptrend=0·036). In addition, a recent study of a small group of exposed workers showed numerical chromosomal aberrations in myeloid progenitor cells (chromosome 7 monosomy, chromosome 8 trisomy) consistent with myeloid leukaemia, and haematological changes in peripheral blood that are indicative of effects on the bone marrow. The Working Group concluded that, overall, there is sufficient evidence for leukaemia, particularly myeloid leukaemia.
Cancer; Cancer-rates; Carcinogens; Epidemiology; Standards; Bladder-disorders; Bladder-cancer; Dyes; Benzidines; Benzopyrenes; Polycyclic-aromatic-hydrocarbons; Rubber-manufacturing-industry; Rubber-workers; Lung-cancer; Blood-disorders; Nasal-cancer; Respiratory-system-disorders
50-32-8; 71-43-2; 1746-01-6; 50-00-0; 57117-31-4; 57465-28-8
Publication Date
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Journal Article
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NIOSH Division
Source Name
The Lancet Oncology
Page last reviewed: May 11, 2023
Content source: National Institute for Occupational Safety and Health Education and Information Division