Jennifer Sass

Meeting Report: Hazard Assessment for Nanoparticles—Report from an Interdisciplinary Workshop

In this report we present the findings from a nanotoxicology workshop held 6–7 April 2006 at the Woodrow Wilson International Center for Scholars in Washington, DC. Over 2 days, 26 scientists from government, academia, industry, and nonprofit organizations addressed two specific questions: what information is needed to understand the human health impact of engineered nanoparticles and how is this information best obtained? To assess hazards of nanoparticles in the near-term, most participants noted the need to use existing in vivo toxicologic tests because of their greater familiarity and interpretability. For all types of toxicology tests, the best measures of nanoparticle dose need to be determined. Most participants agreed that a standard set of nanoparticles should be validated by laboratories worldwide and made available for benchmarking tests of other newly created nanoparticles. The group concluded that a battery of tests should be developed to uncover particularly hazardous properties. Given the large number of diverse materials, most participants favored a tiered approach. Over the long term, research aimed at developing a mechanistic understanding of the numerous characteristics that influence nanoparticle toxicity was deemed essential. Predicting the potential toxicity of emerging nanoparticles will require hypothesis-driven research that elucidates how physicochemical parameters influence toxic effects on biological systems. Research needs should be determined in the context of the current availability of testing methods for nanoscale particles. Finally, the group identified general policy and strategic opportunities to accelerate the development and implementation of testing protocols and ensure that the information generated is translated effectively for all stakeholders.

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substances potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen . The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ‘glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential’. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected. EFSA concluded ‘that there is very limited evidence for an association between glyphosate-based formulations …

Vinyl Chloride: A Case Study of Data Suppression and Misrepresentation

When the U.S. Environmental Protection Agency (EPA) finalized its 2000 update of the toxicological effects of vinyl chloride (VC), it was concerned with two issues: the classification of VC as a carcinogen and the numerical estimate of its potency. In this commentary we describe how the U.S. EPA review of VC toxicology, which was drafted with substantial input from the chemical industry, weakened safeguards on both points. First, the assessment downplays risks from all cancer sites other than the liver. Second, the estimate of cancer potency was reduced 10-fold from values previously used for environmental decision making, a finding that reduces the cost and extent of pollution reduction and cleanup measures. We suggest that this assessment reflects discredited scientific practices and recommend that the U.S. EPA reverse its trend toward ever-increasing collaborations with the regulated industries when generating scientific reviews and risk assessments.

Project TENDR: Targeting Environmental Neuro-Developmental Risks The TENDR Consensus Statement.

Summary: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.

U.S. Department of Defense and White House Working Together to Avoid Cleanup and Liability for Perchlorate Pollution

Abstract The toxic anti-thyroidic chemical perchlorate, used in rocket fuel, has leached from military dumpsites into public drinking water sources, contaminating the water at dangerous levels in many states. The Department of Defense and its contractors such as Lockheed Martin are using obfuscation to wage a campaign to slow or block Environmental Protection Agency regulatory measures that might cost them billions of dollars in cleanup and liability. The influence of the DOD over the EPA is cause for extreme concern.

Industry efforts to weaken the EPA's classification of the carcinogenicity of 1,3-butadiene.

Abstract Industrys success in negotiating away science at the level of governmental regulatory agencies is eroding the integrity of the regulatory process. Maneuvers used by industry to weaken the U.S. Environmental Protection Agencys classification of the carcinogenicity of butadiene are described.

Letter to Dr. Gro Harlem Brundtland, Director-General, WHO

Re : Implementation of WHO Guidelines on Disclosure of Interest by members of WHO Expert Panels.

Statement in response to asbestos industry efforts to prevent a ban on asbestos in Pakistan: chrysotile asbestos use is not safe and must be banned.

We condemn in the strongest possible terms the dangerous misinformation that the International Chrysotile Association is disseminating in its effort to defeat a proposed ban on asbestos in Pakistan. The International Chrysotile Association “actively represents the interest of Chrysotile Industry world over”.1 In a letter dated January 31, 2013 to Dr Mahmood A. Khwaja (Senior Adviser, Chemicals and Sustainable Industrial Development, Sustainable Development Policy Institute of Pakistan), the Chairman of the International Chrysotile Association (Mr Jean-Marc Leblond) expresses the opposition of that Association to the recommendation made, in January 2013, by the Pakistan National Assembly’s Standing Committee on Human Resource Development to ban the import and use of asbestos. Mr Leblond is a long-time salesman of asbestos. From 1986 to 2007, he was Vice President in charge of Sales for LAB Chrysotile Inc., a Quebec asbestos mining company. From 2008 to 2011, he was President of Chrysotile Canada Inc., the marketing agency for Quebec asbestos mining companies. He sat as a director of the discredited asbestos lobby organisation, the Chrysotile Institute. Presently, he is Presi-

SUPPORTING THE NEED FOR RIGOROUS ENFORCEABLE DISCLOSURE POLICIES FOR SCIENTIFIC JOURNALS

John Davies is UK Editor in Chief of Addiction Research and Theory. He is a member of the special health board, National Health Service Quality Improvement Scotland. In the last 3 years he has been in receipt of a Scottish Government grant to measure the social and cultural impact of the Scottish Smokefree legislation, in collaboration with the Universities of Stirling and Central Lancashire. He is a non-executive director of the Glasgow Council on Alcohol. In April 2008 he gave a talk on the concept of addiction to a JTI scientific workshop, for which he was paid. He believes the concept of ‘addiction’ is confused and self-handicapping and has expressed that view in a variety of contexts. Frederick Rotgers is US Editor in Chief of Addiction Research and Theory. He is a member of the New Jersey State Division of Addiction Services Professional Advisory Committee. He has presented numerous workshops on treatment methods and has been paid for those presentations. He will present a workshop at the American Psychological Association Annual Convention in August, 2009, for which he will be paid. He is a strong proponent of harm reduction approaches toward the negative consequences of human substance use, and believes that substance use and misuse need to be addressed from the perspective of the whole person, not primarily as a ‘brain disease’ or other biological entity.

Key elements of effective and practical disclosure policies for health science journals.

Science plays a critical role in arbitrating the safety and efficacy of consumer and industrial products. Just as critical is the role of scientific journals, which can give published science the imprimatur of independence and therefore credibility. Richard Smith, an editor for the British Medical Journal for 25 years, has argued that the drug industry has become reliant on the publication of industry-funded studies that are published in major journals to give the research a “stamp of approval,” distribute the conclusions globally, and even attract media coverage (Smith 2005). “The quality of the journal will bless the quality of the drug,” Smith wrote. Effective disclosure policies play an important role in protecting journals from becoming unwitting agents of propaganda, distortion, corporate marketing, and other types of misinformation, thereby constituting an important cornerstone of their credibility and reputation. In the summer of 2008, the Natural Resources Defense Council (NRDC) hosted a day-long workshop to discuss disclosure policies for health science journals. Participants included journal editors, other journal staff, academic scientists, scientific consultants, ethics experts, and publishing-house representatives. The product of the workshop is an NRDC report (Sass 2009) in which we recommend key elements of an effective and enforceable disclosure policy to guide journals in shaping and refining useful disclosure policies. Here I provide a summary of the results of that workshop. Journal staff should clearly identify how far back they wish their journal policy on competing interests to extend, considering what is appropriate for the journal. Under no circumstances should policies be limited only to current conflicts. The public statement should be no more than a few sentences and should include relevant patents, employment, collaborations, consulting, and so on, that could be seen as a possible competing interests. If no competing interests are disclosed, then this should be stated in the public statement. The disclosure policy should address both financial and nonmonetary relevant competing interests. If authors declare competing interests to the journal, they should also declare approximate monetary value. A strong competing interest policy requires that all authors declare that the manuscript is free from the sponsor’s influence. Many journals already incorporate some kind of statement regarding the role of the funding source. If there was no such involvement, then a statement to that effect could be provided. Disclosure policies should apply to all authors and should also be extended to peer reviewers and journal editors, where “editors” include all of the people who are involved in the peer-review and decision-making processes about articles; this would exclude others involved in the editing process, such as copy editors, managing editors, and proofreaders. For editors and for authors of review articles and editorials, a greater level of scrutiny and public disclosure to the reader is warranted because these circumstances may influence the selection of the science that will be reviewed or published. As a rule of thumb, disclosures must include any financial interests that could constitute a potential source of bias—or of perceived bias—in the eyes of the general public, the media, the scientific community, peer reviewers, or editors. The NRDC (Sass 2009) recommends the following language for requesting disclosures: All financial interests must be disclosed. This includes but is not limited to employment, clients, honoraria, travel expenses, grants, and litigation support. The approximate monetary value of any financial interests must be declared and should distinguish between funding for research and monies paid to the author. Disclosures should include anticipated future competing interests, and past competing interests going back a minimum of three years. Any other competing interests or potentially competing interests, financial or other that, when known to the public could compromise the standing or integrity of the journal, peer reviewers or author should be disclosed. The journal editors will then decide how best to manage these. The public statement (as well as the detailed listing of competing interests) should be written in language such that the average person would be able to identify a potential competing interest. A mere listing of funding sources for a study or the author’s salary or honoraria is not adequate if most readers are not able to establish the link to a potential source of bias. All participants of the NRDC workshop agreed that enforcing a policy is critical to making it effective. All workshop participants agreed that disclosure policies boil down to a mechanism in which disclosure enables peer reviewers and other professionals in the same field to alert journal staff if authors fail to disclose appropriately. If an author is found to have failed to disclose competing interests appropriately and further refuses to disclose in response to a request by the journal staff, punitive methods could include retraction of the article or banning the author from publishing in that journal for a specified length of time. EHP strengthened its policy in 2004 to allow a 3-year ban for authors found to “have willfully failed to disclose a competing interest” (Environmental Health Perspectives 2009). The journal editor could reject the paper at any stage for failure to disclose, and in cases where that failure appears to be deliberate or suspicious, the editor should consider referring the possible infraction to the senior author’s institutional superior for further investigation, along with any relevant documentation. Because the critical issue underlying disclosure is the reliability of the information being reported in a manuscript, NRDC workshop participants also suggested that journals could conduct random audits in which authors of a randomly selected article are asked by the journal for a more detailed data report, potentially including submission of raw data. Many of the most respected scientific and medical journals have instituted effective, practical disclosure policies. Although these policies may differ from journal to journal, they share certain elements that can be adapted to the specific needs of any journal. Given the importance of the scientific literature in guiding consumer and industrial health policy, it should be the goal of all journals to ensure integrity in the articles they publish. Strong disclosure policies are a critical tool for achieving this goal.