Martyn Smith received his PhD in Biochemistry from St. Bartholomew's Hospital in London and did Post-Doctoral training in toxicology at the Karolinska Institute in Stockholm. Dr Smith has expertise in molecular epidemiology, toxicology and genomics, and his research is aimed at finding the causes of chronic diseases, including cancer and diabetes. He currently teaches Advanced Toxicology and mentors graduate students and postdoctoral scholars in the Molecular Toxicology, epidemiology and environmental health programmes. Since 1987, he has been the Director of the NIEHS-funded UC Berkeley Superfund Research Program. The goals of this programme are to improve understanding of the relationship between exposure and disease; improve risk assessments; and, develop prevention and remediation strategies to improve and protect public health and the environment. Dr Smith's current research is in the emerging field of exposomics, but he is perhaps best known for his research on benzene and blood cancers. He also works with international collaborators on using mechanistic data in the identification of human carcinogens. Dr Smith is a Fellow of the American Association for the Advancement of Science. He received the 2010 Children's environmental health Network Award, became an elected Fellow of the Collegium Ramazzini in 2012, and received the Alexander Hollaender Award from the Environmental Mutagenesis and Genomics Society in 2014.

ABSTRACT

Mechanistic data can provide biological plausibility to support epidemiological and animal toxicology findings in identifying cancer risks. However, there is a need for a broadly accepted systematic method for identifying, organizing, and summarizing mechanistic data for the purpose of decision-making in cancer hazard identification. An international Working Group of experts convened by IARC identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. These characteristics provide the basis for an objective approach to identifying and evaluating evidence from pertinent mechanistic studies (Smith et al. Env. Health Perspect. 2015, Nov24). The ten characteristics are distinct from the hallmarks of cancer in reflecting carcinogenic mechanisms rather than the properties of cancer cells, namely the abilities to: (1) act as an electrophile either directly or after metabolic activation; (2) be genotoxic; (3) alter DNA repair or cause genomic instability; (4) induce epigenetic alterations; (5) induce oxidative stress; (6) induce chronic inflammation; (7) be immunosuppressive; (8) modulate receptor-mediated effects; (9) cause immortalization; and (10) alter cell proliferation, cell death, or nutrient supply. The 10 key characteristics are used to systematically search the literature for evidence on relevant endpoints, and support objective evaluation of the overall strength of mechanistic information. Recent IARC monograph evaluations demonstrate the applicability of the approach for mechanistically diverse agents. For some compounds, there was strong evidence for only one (2,4-D) or no (parathion) key characteristics. Interestingly, strong evidence for two key characteristics (genotoxicity, oxidative stress) was found for glyphosate, diazinon and malathion, with malathion additionally showing three others (chronic inflammation, receptor-mediated effects, alters cell proliferation). DDT and TBBPA had strong evidence for a different set of key characteristics (receptor-mediated effects, immunosuppression, and oxidative stress). These developments lay the groundwork for future evaluations, where mechanistic data may fill important gaps in evidence of carcinogenicity.