Meeting report: summary of IARC monographs on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol

An international, interdisciplinary working group of expert scientists met in June 2004 to develop IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. Each IARC Monograph includes a critical review of the pertinent scientific literature and an evaluation of an agent's potential to cause cancer in humans. After a thorough discussion of the epidemiologic, experimental, and other relevant data, the working group concluded that formaldehyde is carcinogenic to humans, based on sufficient evidence in humans and in experimental animals. In the epidemiologic studies, there was sufficient evidence that formaldehyde causes nasopharyngeal cancer, "strong but not sufficient" evidence of leukemia, and limited evidence of sinonasal cancer. The working group also concluded that 2-butoxyethanol and 1-tert-butoxy-2-propanol are not classifiable as to their carcinogenicity to humans, each having limited evidence in experimental animals and inadequate evidence in humans. These three evaluations and the supporting data will be published as Volume 88 of the IARC Monographs.     

A system for evaluating the use of media in CDC's National AIDS Information and Education Program.

The National AIDS Information and Education Program (NAIEP) commissioned the National Academy of Sciences to design a prototypical system of research for use in the evaluation of the agency''s media campaign. It consists of four types of evaluation: formative, efficacy, process, and outcome. These types of evaluations are used to answer such questions as the following: What message strategies will work best? Can a campaign under optimal conditions be expected to make a difference? What interventions are actually delivered during the campaign? Has the campaign actually had an impact? How NAIEP has used the system and adapted it during 1 year of research activities is outlined, and examples from a variety of other social marketing programs are described.     

IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed.Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health.Citation: Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP, Cardis E, Cherrie JW, Christiani DC, Cocco P, Coggon D, Comba P, Demers PA, Dement JM, Douwes J, Eisen EA, Engel LS, Fenske RA, Fleming LE, Fletcher T, Fontham E, Forastiere F, Frentzel-Beyme R, Fritschi L, Gerin M, Goldberg M, Grandjean P, Grimsrud TK, Gustavsson P, Haines A, Hartge P, Hansen J, Hauptmann M, Heederik D, Hemminki K, Hemon D, Hertz-Picciotto I, Hoppin JA, Huff J, Jarvholm B, Kang D, Karagas MR, Kjaerheim K, Kjuus H, Kogevinas M, Kriebel D, Kristensen P, Kromhout H, Laden F, Lebailly P, LeMasters G, Lubin JH, Lynch CF, Lynge E, ‘t Mannetje A, McMichael AJ, McLaughlin JR, Marrett L, Martuzzi M, Merchant JA, Merler E, Merletti F, Miller A, Mirer FE, Monson R, Nordby KC, Olshan AF, Parent ME, Perera FP, Perry MJ, Pesatori AC, Pirastu R, Porta M, Pukkala E, Rice C, Richardson DB, Ritter L, Ritz B, Ronckers CM, Rushton L, Rusiecki JA, Rusyn I, Samet JM, Sandler DP, de Sanjose S, Schernhammer E, Seniori Costantini A, Seixas N, Shy C, Siemiatycki J, Silverman DT, Simonato L, Smith AH, Smith MT, Spinelli JJ, Spitz MR, Stallones L, Stayner LT, Steenland K, Stenzel M, Stewart BW, Stewart PA, Symanski E, Terracini B, Tolbert PE, Vainio H, Vena J, Vermeulen R, Victora CG, Ward EM, Weinberg CR, Weisenburger D, Wesseling C, Weiderpass E, Zahm SH. 2015. IARC Monographs: 40 years of evaluating carcinogenic hazards to humans. Environ Health Perspect 123:507–514; http://dx.doi.org/10.1289/ehp.1409149     

The formaldehyde dilemma

The IARC's 2004 classification of formaldehyde as a human carcinogen has led to intensive discussion on scientific and regulatory levels. In June 2014, the European Union followed and classified formaldehyde as a cause of cancer. This automatically triggers consequences in terms of emission minimization and the health-related assessment of building and consumer products. On the other hand, authorities are demanding and authorizing technologies and products which can release significant quantities of formaldehyde into the atmosphere. In the outdoor environment, this particularly applies to combusting fuels. The formation of formaldehyde through photochemical smog has also been a recognized problem for years. Indoors there are various processes which can contribute to increased formaldehyde concentrations. Overall, legislation faces a dilemma: primary sources are often over-regulated while a lack of consideration of secondary sources negates the regulations’ effects.     

Talking “truth”: Predictors and Consequences of Conversations about a Youth Antismoking Campaign for Smokers and Nonsmokers

Using data from the Legacy Media Tracking Survey II, this study investigated relations among youth's evaluations of the “truth” antismoking campaign, campaign-related interpersonal discussion, and campaign-relevant outcomes (n = 8,000). Regression analyses showed that smokers were less likely to have discussed the campaign than nonsmokers, and this effect was mediated by negative campaign evaluation. However, smokers with a negative evaluation of the campaign were more likely to talk about it than were nonsmokers reporting negative evaluation. Nonsmokers who talked about the campaign had beliefs, attitudes, and intentions in greater agreement with campaign messages than those who did not talk about the campaign. For smokers, talking about the campaign was associated with beliefs, attitudes, and intentions in greater agreement with campaign messages, but only if associated with positive campaign evaluation. For smokers with a negative campaign evaluation, talking about the campaign was associated with beliefs and attitudes counter to the campaign messages.     

Risk perceptions and smoking decisions of adult Chinese men

This study analyzes effects of changes in risk perceptions of smoking's health harms on actual and attempted quits and quitting intentions of male smokers in China. Our survey of 5000+ male smokers was conducted two years after their neighbor's lung cancer diagnosis. We use proximity to a lung cancer neighbor as an exogenous determinant of individual's smoking risk perception. We show that learning of a neighbor's lung cancer diagnosis substantially affects smokers’ subjective beliefs about smoking's harms, which in turn affects decisions about continued smoking and intentions to quit. Our study findings offer important public policy implications in indicating the importance of designing health-warning messages that fit smokers’ personal circumstances as opposed to warnings solely based on edicts from scientific experts and/or epidemiological evidence.     

From phenoxyacetic acids to cellular telephones: is there historical evidence for the precautionary principle in cancer prevention?

In the late 1970s, the author and his colleagues published the first scientific evidence of an association between exposure to phenoxyacetic acids and chlorophenols and certain malignant tumors; the study subjects were also exposed to contaminating dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The results have been corroborated in other studies. Over the years, industry and its allied experts have attacked these studies, but in 1997 IARC classified TCDD as a human carcinogen, Group I. The author and colleagues found an increased risk of non-Hodgkins lymphoma (NHL) for subjects exposed to these chemicals or to some persistent organic pollutants; the increasing incidence in Sweden leveled off in about 1990. The author postulated that the regulation of or ban on these chemicals in Sweden in the 1970s contributed to the now decreasing incidence of NHL. Recent findings of an association between cellular telephones and brain tumors have provoked much unfounded criticism from industry and from the Swedish Radiation Protection Authority. Thus the precautionary principle is prohibited and early warnings of a cancer risk ignored. The experience of cancer risks from certain chlorinated phenols may serve as a model of how the precautionary principle could be used to take early warnings seriously. Unfortunately, the lessons of history seem to go unheeded, as exemplified by the case of cellular telephones.     

Prevention, ethics and science: lessons from Lorenzo Tomatis

This paper is dedicated to Lorenzo Tomatis, former director of the International Agency for Research on Cancer (IARC), promoter of prevention principles with a precautionary approach, supported by an important scientific foundation. He has recommended an appropriate consideration of both "false negatives" and "false positives" errors in the evaluation of epidemiological and experimental data on toxicological and carcinogenic risk. The current rules for IARC Monographs preparation include both a full transparency of the data used and of the possible conflicts of interest of the experts involved. Tomatis has also underlined that "Dismissing animal carcinogenicity findings would lead to human cases as the only means of demonstrating carcinogenicity of environmental agents. This is an unacceptable public health policy". The main role of experimental studies is presently included in both the new preamble of IARC Monographs and the method adopted for the World Health Organization Air Quality Guidelines for low-dose carcinogenic risk assessment.     

The IARC monographs program: changing attitudes towards public health

From its outset, the International Agency for Research on Cancer's (IARC's) program for the evaluation of carcinogenic risks for humans had to resist strong direct and indirect pressures from various sources to protect its independence. External experts for Monographs working groups were selected on the basis of competence and the absence of conflicts of interest. The IARC did not use unpublished or confidential data, so readers could access the original information and thus follow the groups' reasoning. The strength of the original program lay in its scientific integrity and its transparency. Since 1994, however, the IARC appears to have attributed less importance to public health-oriented research and primary prevention, and the Monographs program seems to have lost some of its independence. Criteria for evaluating carcinogenicity related to mechanism(s) of action are not necessarily used as originally intended, to ensure better protection of public health. Evidence for carcinogenicity provided by the results of experimental bioassays has been disregarded on the basis of only suggested mechanistic hypotheses. If tests show those hypotheses to be incorrect, or if they do not account adequately for the wide range of susceptibility in humans, serious consequences for public health may follow.     

Onlineinformationen zur Förderung einer informierten Entscheidung über die Teilnahme an einer Darmkrebsfrüherkennung

Colorectal cancer is one of the most prevalent types of cancer in Germany. The provided governmental program for early detection of colorectal cancer intends to increase the chances of recovery by identifying colorectal cancer at an early, more treatable stage.An information module with quality-assured, balanced, and target-group specific information about colorectal cancer and early detection was designed for the women’s health portal and the men’s health portal of the Federal Center for Health Education (BZgA) to promote informed decision-making. A multilevel and multimethodological procedure was chosen to examine if the information module achieved this intended goal and to evaluate how users and experts experienced the information module. User experience was evaluated using an eye-tracking, retrospective think aloud (RTA) technique combined with a quantitative questionnaire, and experts’ evaluations using a half-standardized questionnaire. Additionally, factors like age, education level, sex, previous experience, and health literacy were analyzed.Altogether, users and experts rated the information module very positive, comprehensible, and informative. Reception of the information module increased the knowledge about colorectal cancer and early detection of colorectal cancer significantly. Therefore, the designed information module provides the crucial basis for an informed decision-making process.     

IARC monographs,industry influence,and upgrading,downgrading, and under-grading chemicals: a personal point of view. International Agency for Research on Cancer

The first IARC Monographs Volume was distributed in 1972, and over the 23 years through 1993, under the leadership of Dr Lorenzo Tomatis, 59 IARC Monographs were completed. During 1977-1979 the author was privileged to lead the program for Volumes 15-22, and participated in the pioneering development of the LARC Preamble and Categories of Evidence. During this era other Chiefs of the IARC Monographs included Claus Agthe, Harri Vainio, Antero Aitio, and Julian Wilbourn. Since then (starting with Volume 62: 1995), a new attitude seems to have pervaded the IARC Monographs program, resulting in an increasing influence of or partiality for industry and a diminishing dedication to public and occupational health and safety concerns, and for primary prevention. Some of this attitude comes from an apparent misguided scientific zest prematurely to endorse purported or hypothetical mechanisms of chemical carcinogenesis or modes of action of chemicals causing cancer in experimental animals. These speculations are in turn used cavalierly to discount the value of experimental evidence for predicting probable carcinogenicity to humans. Most often this is accomplished by opining that the mechanism(s) of carcinogenicity in animals would not be operative in humans. End of explanation. Examples whereby the IARC has recently "down-graded" or "under-graded" the available evidence of carcinogenicity include: acrylonitrile; atrazine; benzidine-based dyes; 1,3-butadiene, dichloromethane (methylene chloride); di (2-ethylhexyl) phthalate; glass wool insulation; MtBE [methyl tertiary butyl ether]; ochratoxin A; saccharin; sunlamps and sunbeds (use of); trichloroethylene; sulfamethazine; and others more inclusively mentioned in the text and tables. Further impeding or compromising public health, chemicals causing site-specific cancers in animals attendant with calculi/precipitate in the urinary bladder, goiter and thyroid gland, kidney and alpha-2mu globulin, peroxisome proliferation and liver tumors, and cell proliferation in general have led the IARC to discount these car- cinogenic effects. To stem this tide at the IARC, new leadership, with more objectivity and public health perspective, is needed.     

The ISS Carcinogens Data Bank (BDC)

The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents.     

Participant recruitment for paediatric research using social media: A practical ‘how-to’ guide for researchers

Aim

Social media platforms are being increasingly used to support participant recruitment into paediatric health-related research. This study aimed to develop a multi-phase approach for using social media as a recruitment strategy for paediatric research studies.

Methods

The process was informed by the authors’ prior experiences recruiting for paediatric obesity-related research studies, expertise in social media marketing and digital participant/ patient recruitment. Reflection on these experiences resulted in the iterative creation of a draft process which was further refined. A narrative literature review using a structured search was conducted to refine and augment the content and finalise the process.

Results

A six-phase recruitment approach was developed that includes: (i) plan for social media use as a recruitment strategy, (ii) explore relevant ethical considerations to protect the wellbeing of potentially vulnerable groups and create an ethical management plan, (iii) identify and understand the different target audiences and develop the advertising strategy, (iv) develop and design campaign content, (v) implement, monitor and iteratively refine the recruitment campaign, (vi) evaluate the campaign success. Potential activities and key considerations relevant for paediatric research are presented within each phase.

Conclusion

Due to the widespread use and diverse characteristics of social media users, social media has the potential to disseminate details of research opportunities to community members who may otherwise not hear about, engage with, and potentially benefit from research participation. Researchers should collaborate with communication experts and target audiences to generate relevant and effective recruitment campaigns. Researchers should implement processes to protect vulnerable audiences’ wellbeing at each stage of the process. Recruitment via social media may support wider community participation in research studies designed to improve young people's health.     

Strategic questions for consumer-based health communications.

Using the consumer-oriented approach of social and commercial marketers, this article presents a process for crafting messages designed to improve people''s health behaviors. The process, termed consumer-based health communications (CHC), transforms scientific recommendations into message strategies that are relevant to the consumer. The core of CHC is consumer research conducted to understand the consumer''s reality, and thereby allowing six strategic questions to be answered. The immediate result of the CHC process is a strategy statement--a few pages that lay out who the target consumer is, what action should be taken, what to promise and how to make the promise credible, how and when to reach him or her, and what image to convey. The strategy statement then guides the execution of all communication efforts, be they public relations, mass media, direct marketing, media advocacy, or interpersonal influence. It identifies the most important "levers" for contact with the consumer. Everyone from creative specialists through management and program personnel can use the strategy statement as a touchstone to guide and judge the effectiveness of their efforts. The article provides a step by step illustration of the CHC process using the 5 A Day campaign as an example.     

Mainstreaming of Emergency Contraception Pill in India: Challenges and Opportunities

Background:

Emergency Contraception Pill (ECP) is an essential intervention to prevent unwanted pregnancies. However, its use has remained low due to various barriers including reservations among medical fraternity.

Materials and Methods:

This paper presents findings on barriers to ECP''s easy access for potential users from (i) a cross-sectional survey of providers'' attitudes, beliefs, and practices and interviews with key opinion leaders, (ii) three consultations organized by Population Council with policymakers and public health experts, and (iii) evidence from scientific literature.

Results:

The major barriers to easy access of ECP include misconceptions and reservations of providers (disapproval of ECP provision by CHWs, opposition to its being an OTC product, and myths, misconceptions, and moral judgments about its users) including influential gynecologists.

Conclusion:

For mainstreaming ECP, the paper recommends educational campaign focusing on gynecologists and CHWs, relaxing restrictive policy on advertisement of ECP, involving press media and strengthening supply chain to ensure its regular supply to ASHA (CHW).     

Marketing HIV Prevention for Heterosexually Identified Latino Men Who Have Sex with Men and Women: The Hombres Sanos Campaign

This article describes the development process of Hombres Sanos, a social marketing campaign to promote HIV testing and condom use for heterosexually identified Latino men who have sex with men and women. The steps included qualitative formative research and a social marketing analytic framework to understand our target audience better, identify incentives and barriers to risk reduction, guide product development, define an optimal promotional campaign, and inform the selection of campaign platforms. A better grasp of the authors' target beneficiaries' needs and values led to an innovative dual strategy for audience segmentation and targeting. The campaign had consumer-centered, culturally sensitive, and theory-driven communication materials. The authors found communication materials and events to be appealing and effective. The campaign was well received among the wider community, and evaluation showed promising results among Latino men in general and among heterosexually identified Latino men who have sex with men and women in particular. The authors provide a step-by-step overview of the project's formative research, including research methods and findings, and how these were translated into a social marketing campaign. In addition, the authors discuss the challenges encountered in this process and the potential of social marketing to reduce HIV risk among Latinos.     

A Critical Perspective on the Drug Czar's Antidrug Media Campaign

The US government's Office of National Drug Control Policy (ONDCP) launched its new antidrug media campaign in July 1998 . The campaign is likely to increase awareness of the youth drug problem , but shortcomings in the campaign's early implementation raise questions about its potential for changing behavior . Short comings include: a) The first wave of ONDCP's television advertisements are focused on reinforcing problem awareness but do not model skills or provide other information necessary for behavior change; b) the campaign provides insufficient focus on promoting drug treatment and citizen involvement in local prevention activities , including political action; c) the campaign is being implemented without a major new investment in drug - treatment programs or community - based prevention programs; d) The campaign does not substantively address alcohol and tobacco , which pose a clear threat to health and serve as a "gateway" to illicit drug use; and e) the first wave of television advertisements use exaggerated fear appeals , a strategy shown by research rarely to be successful . Only time will tell whether the ONDCP media campaign will succeed or fail . Using past research as a guide , there is legitimate reason for concern that the campaign will not live up to expectations .     

Carotenoids in health and disease: recent scientific evaluations, research recommendations and the consumer

In addition to his many research achievements, James Allen Olson made important contributions to evaluations of the role of dietary carotenoids in prevention of chronic diseases such as cancer, heart disease and age-related macular degeneration in well-nourished populations. This paper reviews recent scientific evaluations of the role of carotenoids in disease, recommendations for future research, and consumer-related trends of relevance to carotenoids. Authoritative scientific evaluations by key leading thinkers have not been able to ascribe a disease prevention function to carotenoids because of the absence of definitive evidence. These leading thinkers recommend that future research on the role of carotenoids in disease focus on the complexities of diet, genetics and environment in the disease process. This research is important to make it possible for consumers to derive optimal health promoting benefits from fruits and vegetables in the context of changing dietary patterns.     

Role of experimental and epidemiological evidence of carcinogenicity in the primary prevention of cancer

Experimental chemical carcinogenesis, which included long-term tests in experimental animals,had a dominating role in cancer research between the 1920s and the late 1960s. Two events marked a certain decline of confidence in the ability of experimental results to predict human risks: the incapacity of developing methods to identify agents acting on the different steps of the carcinogenesis process, and the incapacity to reproduce experimentally the strong evidence of carcinogenicity of tobacco smoke provided by epidemiological studies. It was at that time that epidemiologists and biostatisticians developed criteria for assessing the causation of chronic-degenerative diseases relying primarily on epidemiological evidence. In 1969 the International Agency for Research on Cancer (IARC) did initiate a programme for identifying the cause of cancer with the aim of promoting the primary prevention of cancer. The programme is focused on the evaluation of the carcinogenicity of environmental agents on the basis of both the experimental and epidemiological evidence and, since the 1990s, a balanced use of the new tools provided by advances in toxicology, molecular biology and genetics. A strong point of the IARC programme is that in the absence of adequate human data it is reasonable and prudent to regard agents for which there is sufficient experimental evidence of carcinogenicity as if they were carcinogenic to humans.     

Measures of agreement between many raters for ordinal classifications

Screening and diagnostic procedures often require a physician's subjective interpretation of a patient's test result using an ordered categorical scale to define the patient's disease severity. Because of wide variability observed between physicians' ratings, many large‐scale studies have been conducted to quantify agreement between multiple experts' ordinal classifications in common diagnostic procedures such as mammography. However, very few statistical approaches are available to assess agreement in these large‐scale settings. Many existing summary measures of agreement rely on extensions of Cohen's kappa. These are prone to prevalence and marginal distribution issues, become increasingly complex for more than three experts, or are not easily implemented. Here we propose a model‐based approach to assess agreement in large‐scale studies based upon a framework of ordinal generalized linear mixed models. A summary measure of agreement is proposed for multiple experts assessing the same sample of patients' test results according to an ordered categorical scale. This measure avoids some of the key flaws associated with Cohen's kappa and its extensions. Simulation studies are conducted to demonstrate the validity of the approach with comparison with commonly used agreement measures. The proposed methods are easily implemented using the software package R and are applied to two large‐scale cancer agreement studies. Copyright © 2015 John Wiley & Sons, Ltd.