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: Updated Procedures for Modern and Transparent Evidence Synthesis in Cancer Hazard Identification.

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.

Use of mechanistic data in the IARC evaluations of the carcinogenicity of polychlorinated biphenyls and related compounds.

The IARC Monographs are a series of scientific reviews that identify environmental factors that can increase the risk of cancer in humans. In its first part, the principles and procedures of the IARC Monographs evaluations are summarized. In a second part, we present the most recent IARC evaluation of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), performed in February 2013: PCBs and dioxin-like PCBs were both classified into group 1 "carcinogens," while PBBs were evaluated as "probably carcinogenic to humans" (group 2A). Noteworthy is that the relative contributions of different PCB congeners to the carcinogenicity of PCB mixtures are not known. The use of mechanistic data for the classification into a higher category is discussed in the context of the history of the consecutive evaluations of several related polychlorinated compounds.