Research Recommendations for Selected IARC-Classified Agents

Objectives There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. Data sources For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. Data extraction Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. Data synthesis Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. Conclusions Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

[1]  A H Smith,et al.  Diesel exhaust exposure and lung cancer. , 1998, Epidemiology.

[2]  P. Stewart,et al.  Extended mortality follow-up of a cohort of dry cleaners. , 2003, Annals of epidemiology.

[3]  A. Valavanidis,et al.  8-hydroxy-2′ -deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis , 2009, Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews.

[4]  T. Webb,et al.  Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties. , 2007, Toxicology.

[5]  W. Sanderson,et al.  Biological exposure assessment to tetrachloroethylene for workers in the dry cleaning industry , 2008, Environmental health : a global access science source.

[6]  A. Ruder,et al.  Mortality in dry-cleaning workers: an update. , 2001, American journal of industrial medicine.

[7]  R. Budinsky,et al.  Factors related to dioxin and furan body levels among Michigan workers. , 2008, Environmental research.

[8]  R. M. David,et al.  Chronic toxicity of di(2-ethylhexyl)phthalate in rats. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  Patricia A Stewart,et al.  Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries: the National Cancer Institute Cohort. , 2009, Journal of the National Cancer Institute.

[10]  Jenny R. Roberts,et al.  Pulmonary inflammation and tumor induction in lung tumor susceptible A/J and resistant C57BL/6J mice exposed to welding fume , 2008, Particle and Fibre Toxicology.

[11]  R. Vermeulen,et al.  Exposure to atrazine and selected non-persistent pesticides among corn farmers during a growing season , 2009, Journal of Exposure Science and Environmental Epidemiology.

[12]  A. Andersen,et al.  Serum organochlorine levels and breast cancer: a nested case-control study of Norwegian women. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[13]  Ruthann A Rudel,et al.  Environmental Factors in Breast Cancer Supplement to Cancer Chemicals Causing Mammary Gland Tumors in Animals Signal New Directions for Epidemiology , Chemicals Testing , and Risk Assessment for Breast Cancer Prevention , 2007 .

[14]  Weihsueh A. Chiu,et al.  A Reexamination of the PPAR-α Activation Mode of Action as a Basis for Assessing Human Cancer Risks of Environmental Contaminants , 2009, Environmental health perspectives.

[15]  Jürgen Rehm,et al.  Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism. , 2009, Addiction.

[16]  D. Mant Prevention , 1994, The Lancet.

[17]  R. Stevens Light-at-night, circadian disruption and breast cancer: assessment of existing evidence. , 2009, International journal of epidemiology.

[18]  P. Kyyrönen,et al.  Exposure to iron and welding fumes and the risk of lung cancer. , 2008, Scandinavian journal of work, environment & health.

[19]  P. J. Barnes,et al.  Exhaled breath condensate: methodological recommendations and unresolved questions , 2005, European Respiratory Journal.

[20]  P. Danø Introduction to the Symposium on Colloidal Bismuth Subcitrate , 1989 .

[21]  Kurt Straif,et al.  Carcinogenicity of carbon black, titanium dioxide, and talc. , 2006, The Lancet Oncology.

[22]  R W Hornung,et al.  Case-control study of lung cancer and truck driving in the Teamsters Union. , 1990, American journal of public health.

[23]  P. Wild,et al.  Update of a meta-analysis on lung cancer and welding. , 2006, Scandinavian journal of work, environment & health.

[24]  P. Wild,et al.  An epidemiological study of the respiratory health of workers in the European refractory ceramic fibre industry , 2001, Occupational and environmental medicine.

[25]  Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1 to 42. , 1987, IARC monographs on the evaluation of carcinogenic risks to humans. Supplement.

[26]  Mark S. Rea,et al.  Meeting Report: The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases , 2007, Environmental health perspectives.

[27]  A. Naccarati,et al.  Induction of DNA strand breaks by trihalomethanes in primary human lung epithelial cells. , 2003, Mutation research.

[28]  Jang-Ming Lee,et al.  Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid , 2008, International journal of cancer.

[29]  M. Plummer,et al.  International agency for research on cancer. , 2020, Archives of pathology.

[30]  P. Schmezer,et al.  Di(2-ethylhexyl) phthalate. , 1989, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[31]  Ivan Rusyn,et al.  Modes of Action and Species-Specific Effects of Di-(2-ethylhexyl)Phthalate in the Liver , 2006, Critical reviews in toxicology.

[32]  Kurt Straif,et al.  A review of human carcinogens--Part F: chemical agents and related occupations. , 2009, The Lancet. Oncology.

[33]  Martha Waters,et al.  Systematic Literature Review of Uses and Levels of Occupational Exposure to Tetrachloroethylene , 2008, Journal of occupational and environmental hygiene.

[34]  M. Kamijima,et al.  Induction of peroxisome proliferator-activated receptor alpha (PPARα)-related enzymes by di(2-ethylhexyl) phthalate (DEHP) treatment in mice and rats, but not marmosets , 2007, Archives of Toxicology.

[35]  H. Zeeb,et al.  Diesel motor emissions and lung cancer mortality—Results of the second follow‐up of a cohort study in potash miners , 2009, International journal of cancer.

[36]  I. O'neill,et al.  Preamble to the IARC Monographs , 2009 .

[37]  C. Croce Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[38]  Debra Silverman,et al.  Bladder cancer and exposure to water disinfection by-products through ingestion, bathing, showering, and swimming in pools. , 2006, American journal of epidemiology.

[39]  S. Mayne,et al.  Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. , 2003, The Journal of nutrition.

[40]  V. Cogliano Assessing the cancer risk from environmental PCBs. , 1998, Environmental health perspectives.

[41]  Michael Smolensky,et al.  Biological Clocks and Shift Work: Circadian Dysregulation and Potential Long-term Effects , 2006, Cancer Causes & Control.

[42]  T. Carreón-Valencia Formaldehyde exposure and leukemia : a new meta-analysis and potential mechanisms , 2022 .

[43]  Nathaniel Rothman,et al.  A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues , 1997, The Lancet.

[44]  M. Kogevinas,et al.  Disinfection Byproducts and Bladder Cancer: A Pooled Analysis , 2004, Epidemiology.

[45]  A. Sigurdson,et al.  Increased frequency of chromosome translocations in airline pilots with long-term flying experience , 2008, Occupational and Environmental Medicine.

[46]  A. Ruder Potential Health Effects of Occupational Chlorinated Solvent Exposure , 2006, Annals of the New York Academy of Sciences.

[47]  A. Ruder,et al.  Mortality among Workers Exposed to Polychlorinated Biphenyls (PCBs) in an Electrical Capacitor Manufacturing Plant in Indiana: An Update , 2005, Environmental health perspectives.

[48]  M. Salaspuro Acetaldehyde as a common denominator and cumulative carcinogen in digestive tract cancers , 2009, Scandinavian journal of gastroenterology.

[49]  H. Muhle,et al.  Asbestos as reference material for fibre-induced cancer , 2000, International archives of occupational and environmental health.

[50]  F. Stickel,et al.  “Allgemeine und systematische Pharmakologie und Toxikologie” WS 18/19 Seminarthema: Chemische Kanzerogenese , 2017 .

[51]  Vincent Castranova,et al.  Surface area of particle administered versus mass in determining the pulmonary toxicity of ultrafine and fine carbon black: comparison to ultrafine titanium dioxide , 2009, Particle and Fibre Toxicology.

[52]  C. Francia,et al.  The oxidation of glutathione by cobalt/tungsten carbide contributes to hard metal-induced oxidative stress , 2008, Free radical research.

[53]  K. McMartin,et al.  Formaldehyde Expert Panel Report Part B-Recommendation for Listing Status for Formaldehyde and Scientific Justification for the Recommendation , 2009 .

[54]  L. Kupper,et al.  Accumulation of M1dG DNA adducts after chronic exposure to PCBs, but not from acute exposure to polychlorinated aromatic hydrocarbons. , 2008, Free radical biology & medicine.

[55]  P. Grover,et al.  Genotoxic evaluation of welders occupationally exposed to chromium and nickel using the Comet and micronucleus assays. , 2004, Mutagenesis.

[56]  N. Rothman,et al.  Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma: a report from three cohorts. , 2007, Cancer research.

[57]  M. Coye,et al.  NATIONAL RESEARCH COUNCIL AND INSTITUTE OF MEDICINE , 1998 .

[58]  Yuki Ito,et al.  Different Mechanisms of DEHP‐induced Hepatocellular Adenoma Tumorigenesis in Wild‐type and Pparα‐null Mice , 2008, Journal of occupational health.

[59]  Charles L Geraci,et al.  Issues in the Development of Epidemiologic Studies of Workers Exposed to Engineered Nanoparticles , 2009, Journal of occupational and environmental medicine.

[60]  T H Shepard,et al.  National toxicology program. , 1981, Teratology.

[61]  G. M. Wells Styrene. , 2018, Report on carcinogens : carcinogen profiles.

[62]  Peter A. Jones,et al.  The Epigenomics of Cancer , 2007, Cell.

[63]  Wolfgang Kreyling,et al.  Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells , 2005, Environmental health perspectives.

[64]  Lesley A. Mathews,et al.  Epigenetic gene regulation in stem cells and correlation to cancer. , 2009, Differentiation; research in biological diversity.

[65]  J. Lubin,et al.  Cancer incidence among pesticide applicators exposed to atrazine in the Agricultural Health Study. , 2004, Journal of the National Cancer Institute.

[66]  G. Mol,et al.  Levels of Trypsin and α-Chymotrypsin in Feces from Patients with Crohn’s Disease , 1982 .

[67]  Michael Dourson,et al.  Data considerations for regulation of water contaminants. , 2006, Toxicology.

[68]  J. Harrington,et al.  A "lugged" analysis of lung cancer risks in UK carbon black production workers, 1951-2004. , 2007, American journal of industrial medicine.

[69]  G. Wells Propylene oxide. , 2018, IARC monographs on the evaluation of carcinogenic risks to humans.

[70]  M Lipsett,et al.  Occupational exposure to diesel exhaust and lung cancer: a meta-analysis. , 1999, American journal of public health.

[71]  Y. Nishiwaki,et al.  Exposure to hardly soluble indium compounds in ITO production and recycling plants is a new risk for interstitial lung damage , 2007, Occupational and Environmental Medicine.

[72]  Roel P F Schins,et al.  Genotoxicity of Poorly Soluble Particles , 2007, Inhalation toxicology.

[73]  A. Zhitkovich,et al.  Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. , 2008, Chemical research in toxicology.

[74]  M. Imbriani,et al.  Gases and organic solvents in urine as biomarkers of occupational exposure: a review , 2005, International archives of occupational and environmental health.

[75]  J. Antonini,et al.  Health Effects of Welding , 2003, Critical reviews in toxicology.

[76]  Ipcs,et al.  Di(2-ethylhexyl) phthalate. , 2011, Report on carcinogens : carcinogen profiles.

[77]  Inorganic and organic lead compounds. , 2006, IARC monographs on the evaluation of carcinogenic risks to humans.

[78]  T. Chonan,et al.  Interstitial pulmonary disorders in indium-processing workers , 2006, European Respiratory Journal.

[79]  S. Scholz,et al.  Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes , 2010, BMC Genomics.

[80]  I. Yu,et al.  Gene-Expression Profiling of Human Mononuclear Cells from Welders Using cDNA Microarray , 2007, Journal of toxicology and environmental health. Part A.

[81]  N. Sathiakumar,et al.  An updated study of mortality among North American synthetic rubber industry workers , 2005, Occupational and Environmental Medicine.

[82]  L. R. Glass,et al.  Multiple-dose chronic inhalation toxicity study of size-separated kaolin refractory ceramic fiber in male Fischer 344 rats. , 1995, Inhalation toxicology.

[83]  Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children — 1999 , 1999 .

[84]  Francine Laden,et al.  Lung Cancer and Vehicle Exhaust in Trucking Industry Workers , 2008, Environmental health perspectives.

[85]  Eileen Kuempel,et al.  An Approach to Risk Assessment for TiO2 , 2007, Inhalation toxicology.

[86]  A. Okun,et al.  Mortality patterns among workers exposed to styrene in the reinforced plastic boatbuilding industry: an update. , 2004, American journal of industrial medicine.

[87]  L. Hudson,et al.  Oxidative stress and apoptosis in metal ion-induced carcinogenesis. , 2004, Free radical biology & medicine.

[88]  M. Roller,et al.  Classification of man-made vitreous fibers: Comments on the revaluation by an IARC working group. , 2005, Regulatory toxicology and pharmacology : RTP.

[89]  H. Kolstad Nightshift work and risk of breast cancer and other cancers--a critical review of the epidemiologic evidence. , 2008, Scandinavian journal of work, environment & health.

[90]  R. Hayes,et al.  Benzidine-DNA adduct levels in human peripheral white blood cells significantly correlate with levels in exfoliated urothelial cells. , 1997, Mutation research.

[91]  DB Warheit,et al.  Pulmonary toxicity screening studies in male rats with TiO2 particulates substantially encapsulated with pyrogenically deposited, amorphous silica , 2005, Particle and Fibre Toxicology.

[92]  Kengo Watanabe,et al.  Analysis of DNA adducts formed in vivo in rats and mice from 1,2-dibromoethane, 1,2-dichloroethane, dibromomethane, and dichloromethane using HPLC/accelerator mass spectrometry and relevance to risk estimates. , 2007, Chemical research in toxicology.

[93]  Jenny R. Roberts,et al.  Pulmonary Responses to Welding Fumes: Role of Metal Constituents , 2004, Journal of toxicology and environmental health. Part A.

[94]  David M. Brown,et al.  Proinflammogenic Effects of Low-Toxicity and Metal Nanoparticles In Vivo and In Vitro: Highlighting the Role of Particle Surface Area and Surface Reactivity , 2007, Inhalation toxicology.

[95]  T. Schnorr,et al.  Mortality and Exposure Response among 14,458 Electrical Capacitor Manufacturing Workers Exposed to Polychlorinated Biphenyls (PCBs) , 2006, Environmental health perspectives.

[96]  G. Olsen,et al.  Mortality from pancreatic and lymphopoietic cancer among workers in ethylene and propylene chlorohydrin production. , 1997, Occupational and environmental medicine.

[97]  M. Berger,et al.  Lifelong exposure to di-(2-ethylhexyl)-phthalate induces tumors in liver and testes of Sprague-Dawley rats. , 2005, Toxicology.

[98]  L. Robertson,et al.  Metabolic Activation of PCBs to Carcinogens in Vivo - A Review. , 2008, Environmental toxicology and pharmacology.

[99]  J. Angerer,et al.  Human biomonitoring: state of the art. , 2007, International journal of hygiene and environmental health.

[100]  G. Lemasters,et al.  Mortality of Workers Occupationally Exposed to Refractory Ceramic Fibers , 2003, Journal of occupational and environmental medicine.

[101]  P. Boogaard,et al.  Biomonitoring of exposure to ethylene oxide and propylene oxide by determination of hemoglobin adducts: correlations between airborne exposure and adduct levels , 1999, International archives of occupational and environmental health.

[102]  J. Heyder,et al.  Instillation of Six Different Ultrafine Carbon Particles Indicates a Surface Area Threshold Dose for Acute Lung Inflammation in Mice , 2005, Environmental health perspectives.

[103]  K. Czene,et al.  Analysis of DNA and hemoglobin adducts and sister chromatid exchanges in a human population occupationally exposed to propylene oxide: a pilot study. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[104]  Kurt Straif,et al.  A review of human carcinogens--part D: radiation. , 2009, The Lancet. Oncology.

[105]  V. Castranova,et al.  Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area , 2008, Particle and Fibre Toxicology.

[106]  C. Croce,et al.  MicroRNAs in Cancer. , 2009, Annual review of medicine.