The Science of Dioxin

December 27, 2015 | Complex Torts & Product Liability

Paper Proposes “Key Characteristics” of Carcinogens – Epidemiological Evidence Not Required

A paper published in “Environmental Health Perspectives” entitled, “Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis,” has proposed 10 key characteristics that, it said, are “commonly exhibited by established human carcinogens.”

Background

The paper is by Martyn T. Smith, Kathryn Z. Guyton, Catherine F. Gibbons, Jason M. Fritz, Christopher J. Portier, Ivan Rusyn, David M. DeMarini, Jane C. Caldwell, Robert J. Kavlock, Paul Lambert, Stephen S. Hecht, John R. Bucher, Bernard W. Stewart, Robert Baan, Vincent J. Cogliano, and Kurt Straif. The authors are from institutions ranging from the Division of Environmental Health Sciences at the School of Public Health at the University of California in Berkeley, California, and the International Agency for Research on Cancer in Lyon, France, to the Department of Veterinary Integrative Biosciences at the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University in College Station, Texas, and the National Toxicology Program of the National Institute of Environmental Health Sciences at Research Triangle Park in North Carolina.

The authors stated in their paper that a recent review by the International Agency for Research on Cancer (“IARC”) that updated the assessments of the more than 100 agents classified as Group 1, carcinogenic to humans, was “complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens.”

The IARC, therefore, convened two workshops in which an international working group identified 10 key characteristics, one or more of which the authors said in their paper are “commonly exhibited by established human carcinogens.”

According to the paper, these characteristics provide the basis for an “objective approach” to identifying and organizing results from pertinent studies.

The 10 characteristics identified in the paper are the abilities of an agent 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 balance of the authors’ paper describes these 10 characteristics in more detail, stating that they are properties that “human carcinogens commonly show and can encompass many different types of mechanistic endpoints,” but that they are “not mechanisms in and of themselves nor are they adverse outcome pathways.”

The paper also describes how the characteristics “can provide a basis for systematically identifying, organizing, and summarizing mechanistic information as part of the carcinogen evaluation process.”

Significant Issues

There are three particularly notable points to be taken from the paper.

First, in asserting a need for these characteristics, the authors conceded that, in their absence, databases “present a challenge to systematic reviews in that the studies are typically both numerous and diverse, reporting on a multitude of endpoints and toxicity pathways.”

Second, the authors argued that using the 10 characteristics “should introduce objectivity that could reduce reliance on expert opinion, as well as facilitate comparisons across agents,” albeit without focusing “narrowly on independent mechanistic hypotheses or pathways in isolation.”

Finally, the authors concluded that their approach would assist future IARC Working Groups and other agencies in evaluating agents as potential human carcinogens “especially in the absence of convincing epidemiological data on cancer in humans.”

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Compromised Samples Led to Incinerator’s False High Emission Results, Report Finds

High emission results from a new, state-of-the-art $286-million solid waste-to energy incinerator operating in Southern Ontario near Toronto resulted from compromised samples, a report has found. Read more…

Background

Covanta Durham York Renewable Energy Limited built and operates the facility, which can process up to 140,000 tons of waste each year, generating some 17.5 megawatts of renewable energy – enough to power between 10,000 and 12,000 homes.

Emissions measurements taken in September and October from the facility, which is owned by the regional municipalities of Durham and York, showed higher levels of dioxin and furan than had been expected.

Covanta asked ORTECH Environmental to investigate.

The Report’s Conclusions

In its report, ORTECH said that archived samples from the older tests were analyzed by an independent laboratory that found the “presence of interference” in the samples.

The samples were contaminated by chlorinated diphenyl ethers (“DPEs”) and PCB-169 (a polychlorinated biphenyl isomer), which led to the faulty dioxin and furan readings, according to the report.

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