kc-hits: a tool to aid in the evaluation and classification of chemical carcinogens.

MOTIVATION: The evaluation of chemicals for their carcinogenic hazard requires the analysis of a wide range of data and the characterization of these results relative to the key characteristics of carcinogens. The workflow used historically requires many manual steps that are labor-intensive and can introduce errors, bias and inconsistencies. RESULTS: The automation of parts of the evaluation workflow using the kc-hits software has led to significant improvements in process efficiency, as well as more consistent and comprehensive results. AVAILABILITY AND IMPLEMENTATION: https://gitlab.com/i1650/kc-hits.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The IARC Monographs on the carcinogenicity of crystalline silica.

BACKGROUND: Through extensive review of the published literature, two independent expert panels convened by the International Agency for Research on Cancer (IARC) Monographs Programme have classified crystalline silica as carcinogenic to humans while amorphous silica was not classifiable as to its carcinogenicity in humans. The panel remarked that crystalline silica in the form of quartz or cristobalite dust causes lung cancer in humans. OBJECTIVES: We discuss the literature and rationale used to support the IARC evaluations of silica. METHODS: A critical review, with a focus on lung tumors, was conducted of the pertinent literature on the carcinogenic effects of crystalline silica in humans and experimental animals as well as supportive mechanistic evidence. RESULTS: The strongest supportive evidence comes from pooled and meta-analyses that employed quantitative exposure assessment, focused on silicotics, accounted for potential confounding and demonstrated exposure-response trends. Consistency of the effect was observed despite some heterogeneity between individual studies. Tumor site concordance was observed with rodents and further supported by mechanistic data. CONCLUSIONS: Several million workers worldwide are exposed to crystalline silica. Silicosis and lung cancer in these workers are completely preventable diseases. The IARC evaluations are critical to supporting public health interventions to protect persons at high-risk.

Cancer in experimental animals exposed to arsenic and arsenic compounds.

Inorganic arsenic is a ubiquitous environmental contaminant that has long been considered a human carcinogen. Recent studies raise further concern about the metalloid as a major, naturally occurring carcinogen in the environment. However, during this same period it has proven difficult to provide experimental evidence of the carcinogenicity of inorganic arsenic in laboratory animals and, until recently, there was considered to be a lack of clear evidence for carcinogenicity of any arsenical in animals. More recent work with arsenical methylation metabolites and early life exposures to inorganic arsenic has now provided evidence of carcinogenicity in rodents. Given that tens of millions of people worldwide are exposed to potentially unhealthy levels of environmental arsenic, in vivo rodent models of arsenic carcinogenesis are a clear necessity for resolving critical issues, such as mechanisms of action, target tissue specificity, and sensitive subpopulations, and in developing strategies to reduce cancers in exposed human populations. This work reviews the available rodent studies considered relevant to carcinogenic assessment of arsenicals, taking advantage of the most recent review by the International Agency for Research on Cancer (IARC) that has not yet appeared as a full monograph but has been summarized (IARC, 2009 , IARC Special Report: Policy, Vol. 10. Lyon: IARC Press, 453­454). Many valid studies show that arsenic can interact with other carcinogens/agents to enhance oncogenesis, and help elucidate mechanisms, and these too are summarized in this review. Finally, this body of rodent work is discussed in light of its impact on mechanisms and in the context of the persistent argument that arsenic is not carcinogenic in animals.