List of classifications, Volumes 1– – IARC
ADVISORY GROUP TO PLAN VOLUME A REVIEW OF HUMAN Gemma Vestal, WHO Tobacco Free Initiative, Geneva . a review of the human carcinogens that have been identified to date. The th . cancer at certain sites to specific carcinogens should not be viewed as precluding the possi-. This work will be published in as Volume of the IARC IARC's review provides up-to-date information on cancer sites To complete the list of cancer sites with limited evidence, we [PMC free article] [PubMed]. Part F of Volume of the IARC Monographs on the Evaluation of Volume compiles information on tumour sites and mechanisms of carcinogenesis. present volume were last reviewed during IARC Monograph meetings dating from to the release of free benzidine – a re-affirmed Group-1 carcinogen – and to the.
It was noted that since that time none of these cohorts nor any other isopropanol-manufacturing unit has been evaluated for cancer mortality or incidence without the inclusion in the study population of workers in other production units. An increased incidence of other cancers in the upper respiratory tract was observed in these studies, but it was not possible to attribute these cancers to exposures during isopropanol production.
Therefore, the possible association of these tumours with this specific exposure could not be evaluated. The Working Group reviewed more than epidemiological studies of benzene and confirmed its carcinogenicity, with sufficient evidence for acute non-lymphocytic leukaemia and limited evidence for acute and chronic lymphocytic leukaemia, multiple myeloma, and non-Hodgkin lymphoma. The Working Group noted the extraordinary expansion in the epidemiological literature on benzene-related cancers since the previous evaluation, the diversity of industrial and environmental exposure scenarios where benzene has been studied, and the evolution in the histological classification of leukaemias and lymphoid neoplasms over the past decades, and suggested that a re-evaluation of the cancer hazards from exposure to benzene be conducted in due time.
Dioxin 2,3,7,8-tetrachlorodibenzo-para-dioxin, TCDD was previously classified in Group 1, 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 AhRwhich leads to changes in gene expression, cell replication, and apoptosis. There is now sufficient evidence from epidemiological studies for all cancers combined, making TCDD the first agent classified initially in Group 1 based on sufficient evidence of carcinogenicity in experimental animals and strong mechanistic data, to be later confirmed by increased cancer incidence in humans.
This highlights the ability of mechanistic information to provide robust evidence of carcinogenicity.
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The Working Group classified these two chemicals in Group 1. The Working Group discussed the possibility of evaluating an additional 26 polychlorinated dibenzodioxins, dibenzofurans and biphenyls for carcinogenicity, based upon data showing similarity to the mechanism outlined for TCDD. According to the IARC Monographs Preamble, Part B, Section 6dan evaluation may be made for a broad group of agents, even including substances for which there is no direct information on cancer in humans or experimental animals, if it is warranted by the overall evidence.
The Working Group suggested that a future generic evaluation be focused on the entire class of dioxin-like compounds, taking into account the available mechanistic data.
Agents Classified by the IARC Monographs, Volumes 1– – IARC
The Working Group unanimously reaffirmed the classification of formaldehyde in Group 1, based on sufficient evidence in humans of nasopharyngeal cancer. Since that time, the epidemiological evidence has become stronger: In addition, a recent study of a small group of workers exposed to formaldehyde showed numerical chromosomal aberrations in myeloid progenitor cells chromosome-7 monosomy, chromosome-8 trisomyas also observed in myeloid leukaemia, and haematological changes in peripheral blood that are indicative of effects on the bone marrow.
A small majority of the Working Group concluded that, overall, there is sufficient evidence of a causal association between exposure to formaldehyde and an increased risk for leukaemia, particularly myeloid leukaemia. Identification of tumour sites One of the goals of the review of Group-1 carcinogens in Volume of the IARC Monographs is the identification of tumour sites with sufficient evidence in humans.
The tumour-site identification in this volume was — naturally — limited by the research that has been published to date, and it should be noted that many plausible tumour sites identified in rodents have not been considered in humans. For example, several aromatic amines induce mammary gland tumours in rats, and there is mechanistic evidence that supports a potential for aromatic amines to cause this cancer, but the epidemiological studies on cancer associated with exposure to these substances have not considered breast cancer, mainly because the industrial cohorts were generally small and did not include women.
In addition, no case—control studies are available on breast cancer associated with exposure to aromatic amines. Similarly, mammary gland tumours are the only tumour induced by 1,3-butadiene in both rats and mice, but epidemiological studies — while demonstrating an increased risk for leukaemia — have just started to explore the possibility of this chemical being associated with breast cancer.
Changes in occupational exposures over time Changes in occupational hygiene or industrial processes can alter the profile of workplace exposures over time. Moreover, regulations and working conditions may differ greatly from one country to another.
IARC Monographs – News
For these reasons, it is useful to identify the specific agents responsible for excess cancer risks whenever possible see Preamble Part B, Section 6a. It is important to recognize that new studies of modern and improved workplaces would not reflect risks that might still exist in areas where adequate regulations or process improvements are not fully implemented.
Consequently, previous evaluations of occupations that were classified as carcinogenic to humans stand as a historical record of hazards that are known to cause cancer.
In future monographs, as historical exposures described as occupations are reduced and risk is abated, previous findings should be noted as indicative of potential carcinogenic risk in this occupation should historical exposure levels return or continue to exist elsewhere. Also, as industrial processes change, carcinogenicity profiles in the workplace will change and evaluations need to account for these changing processes.
Incorporation of new mechanistic data in future evaluations The ever-increasing understanding of the molecular mechanisms underpinning the classical concepts of initiation, promotion and progression in cancer provides a challenge for its integration into cancer-hazard identification. In most instances, the genotoxic pathways have been considered central to the carcinogenic process and mechanistic studies characterizing these outcomes have provided important supporting information for the evaluation.
IARC's review provides up-to-date information on cancer sites associated with each human carcinogen. There has been debate over the value of identifying cancer sites associated with an agent, with some scientists arguing that association with some cancer sites implies exclusion of a possible association with cancer at other sites 9 The crux of the matter is whether to regard a list of cancer sites restrictively, as a finite number of sites where carcinogenesis is possible, or expansively, as examples where strong evidence of an association exists at the time of evaluation IARC has taken the expansive view, and its recent review provides information pertinent to this question.
In this article, we have brought together cancer site information on more than human carcinogens identified through 40 years of IARC Monographs reviews, rearranged this information to list the known and suspected causes of cancer at various sites, and discussed some implications for the state-of-the-science of carcinogen identification.
Other factors associated with an increased cancer risk not covered in the IARC Monographs, notably genetic traits, reproductive status, and some nutritional factors, are not included in this review. For the purposes of this analysis, sufficient evidence in humans means that a causal relationship has been established and that chance, bias, and confounding could be ruled out with reasonable confidence, whereas limited evidence in humans means that a causal relationship was credible but that chance, bias, or confounding could not be ruled out with reasonable confidence 2.
To complete the list of cancer sites with limited evidence, we searched IARC Monographs Volumes 1—99 for agents that were classified as probably carcinogenic or possibly carcinogenic to humans. In most cases, the cancer site associations are clear and are based on the published summary and evaluation by the most recent Working Group that has classified an agent. For some agents with positive findings for several cancer sites, we made a judgment based on the IARC reviews about which cancer sites might be considered to have a credible causal relationship.
As we searched Volumes 1—99, we found earlier assessments of most carcinogens reviewed in Volume 1. Some Organophosphate Insecticides and Herbicides We are pleased to announce that the Monograph on glyphosate is now available online.
Read the IARC press release.
Preventable Exposures Associated With Human Cancers
This user-friendly, searchable format allows all the agents evaluated in Volumes 1— to be sorted by name, group, CAS number, Monograph volume, and year. The remaining Monographs of volume will be published subsequently. For details, please see Information on nominations.
Some Drugs and Herbal Products We are pleased to announce that the Monographs on Pioglitazone and rosiglitazone, and Digoxin, are now available online. The remaining Monographs will be published subsequently. Read the IARC news item. These instructions should be read in conjunction with the Preamble to the IARC Monographswhich provides guidelines for the selection, evaluation, and integration of data for the Monographs.