Review of the Evidence from Epidemiology, Toxicology, and Lung Bioavailability on the Carcinogenicity of Inhaled Iron Oxide Particulates

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• 作者：Camilla Pease ; Thomas Rücker ; Thomas Birk
• 刊名：Chemical Research in Toxicology
• 出版年：2016
• 出版时间：March 21, 2016
• 年：2016
• 卷：29
• 期：3
• 页码：237-254
• 全文大小：549K
• 年卷期：
  Dr. Camilla Pease
  is a Eurotox Registered Toxicologist and Chartered Chemist with >23 years’ experience in chemical toxicology and >15 years in human health risk assessment. She works as a senior manager and consultant toxicologist for Ramboll Environ in the UK, prior to that was Principal Toxicologist at the Environment Agency (England & Wales), and is an internationally respected health scientist in the areas of human toxicology, human metabolism, and bioavailability. Dr Pease is experienced at developing novel human health risk assessment frameworks for safety decision making in both private industry and regulatory contexts.
  Thomas Rücker
  is a senior manager at Ramboll Environ. His focus is on the hazard and risk assessment of chemicals and consumer products. He provides strategic and regulatory support for chemical companies covering a wide range of products including auxiliaries for industry, specialty chemicals, petrochemicals and derivatives, basic inorganics, and consumer chemicals. In this context, he practices within the core group of the Chemical Safety & Regulatory Compliance practice area of Ramboll Environ. Dr. Rücker has a Diploma in Biology from the University of Kiel, a doctoral degree in Biochemistry from Bonn University, and is a European Registered Toxicologist (ERT) and Diplomate of the American Board of Toxicology (DABT).
  Thomas Birk
  is a senior manager at Ramboll Environ. His focus is on the hazard and risk assessment of chemicals. Mr. Birk has more than 20 years of professional experience in the application of epidemiological concepts and methods, with particular expertise in the areas of occupational and environmental health research, exposure assessment, and quality-based critical reviews of epidemiological literature. He provides strategic and regulatory support for chemical companies in the process of registration and authorization of chemicals under the EU REACH regulation. Mr. Birk has a Diploma Social Sciences from the University of Bochum.
• ISSN：1520-5010

文摘

Since the iron-age and throughout the industrial age, humans have been exposed to iron oxides. Here, we review the evidence from epidemiology, toxicology, and lung bioavailability as to whether iron oxides are likely to act as human lung carcinogens. Current evidence suggests that observed lung tumors in rats result from a generic particle overload effect and local inflammation that is rat-specific under the dosing conditions of intratracheal instillation. This mode of action therefore, is not relevant to human exposure. However, there are emerging differences seen in vitro, in cell uptake and cell bioavailability between “bulk” iron oxides and “nano” iron oxides. “Bulk” particulates, as defined here, are those where greater than 70% are >100 nm in diameter. Similarly, “nano” iron oxides are defined in this context as particulates where the majority, usually >95% for pure engineered forms of primary particulates (not agglomerates), fall in the range 1–100 nm in diameter. From the weight of scientific evidence, “bulk” iron oxides are not genotoxic/mutagenic. Recent evidence for “nano” iron oxide is conflicting regarding genotoxic potential, albeit genotoxicity was not observed in an in vivo acute oral dose study, and “nano” iron oxides are considered safe and are being investigated for biomedical uses; there is no specific in vivo genotoxicity study on “nano” iron oxides via inhalation. Some evidence is available that suggests, hypothetically due to the larger surface area of “nano” iron oxide particulates, that toxicity could be exerted via the generation of reactive oxygen species (ROS) in the cell. However, the potential for ROS generation as a basis for explaining rodent tumorigenicity is only apparent if free iron from intracellular “nano” scale iron oxide becomes bioavailable at significant levels inside the cell. This would not be expected from “bulk” iron oxide particulates. Furthermore, human epidemiological evidence from a number of studies suggests that iron oxide is not a human carcinogen, and therefore, based upon the complete weight of evidence, we conclude that “bulk” iron oxides are not human carcinogens.