Session 1 Q&A and Resources
Answers to questions submitted by participants:
Q: Do exposure assessments currently consider ocean dumping of chlorinated hydrocarbons (dioxin, PCBs, and DDT), and associated pathways of fish ingestion by humans, fish meal fed to chickens, pigs, and other large animals?
A: That’s a great question. There are approaches that address toxic exposures from fish ingestion. But you may be thinking about a bigger picture than many risk assessments currently take. In part that’s because regulations are focused on individual chemicals in individual media (air, water, soil).
Q: Would you mind talking about the precautionary principle and how it being applied in some places and not in others affects work and chemical classification from an international level?
A: Thanks for this great question. IARC’s classification process that I discussed is hazard identification - regulation based on the precautionary principle is part of a later step in the evidence to action process. I hope that helps.
Q: The IARC poster on "Human cancers known causes and prevention" is an amazing resource! I noticed that avoiding the carcinogenic agents is not highlighted as a preventive approach (except for smoking)- why is that?
A: Thanks for this great question. The green items are those evaluated by the IARC Handbooks Program.
Q: Why are these chemicals still allowed on the market and used in makeup, cleaning supplies and personal care products and more? Even if they are 'possible' carcinogens they should be banned.
A. Thanks for this comment. The decision to take action (including to ban or not) would be the decision of governments. As Dr. Kripke noted and remains true, no action has been taken on many Group 1 carcinogens.
Q: Now genetically modified species that have elements of human genome and/or organs/organoids as test media.
A: Thanks for this comment. Yes, these models offer opportunities for progress.
Q: Would/does your 2009 paper allow us to look at CA clusters (cancers of different types in smaller communities) differently?
A: Thanks for this great question. CA clusters remain a significant challenge and there could be opportunities using the key characteristics of carcinogens to help discern causes.
Q: Thank you, Dr. Guyton. How is glyphosate an active ingredient in many pesticides currently categorized by IARC and US EPA? In addition to agriculture, many plant nurseries and landscapers promote its use by homeowners. How should medical and public health professionals talk about glyphosate with the general public?
A: Thanks for this question. IARC classified glyphosate as Group 2A, in part based on studies of occupational settings. This highlights the need to protect workers from known and suspected carcinogens, including pesticides.
Q: For Dr. Guyton. The US EPA has a requirement under TSCA to move away from the use of animal testing by 2035. EU Parliament just passed a resolution to draw up an action plan to end the use of animal testing. What do you think this will mean regarding our current dependency on in vivo data for carcinogen classification? Do you think we’ll be able to implement the characteristics of carcinogens w/in vitro?
A: Thanks for your question. As I said, most carcinogens have been identified from animal bioassays. All human carcinogens have been positive in animal bioassays when tested adequately. There are challenges for building confidence in alternative methods but also opportunities the new approaches bring for identifying suspected carcinogens.
Q: How can we encourage regulatory agencies in the US to use key characteristics/mechanistic data to identify/classify carcinogens?
A: Great question. The key characteristics afford opportunities for authoritative reviews, which are the cornerstone of regulation, and are already being applied such as in the US EPA’s IRIS program as well as NTP’s Report on Carcinogens. I’m hopeful there will be progress and evolution through these experiences.
Q: Do you think with women’s increasing role in the workforce there will be more studies?
A: Great question. Dr. Terry might be able to answer this in more detail - already there is a lot of work ongoing, e.g., in women firefighters. There remain challenges due to sample size (there are often more men in any given setting) and exposure characterization (women may not work the same routine schedule). There are definitely opportunities for shorter term biomarker studies.
Q: What are some potential options that people are considering to help expand the throughput of carcinogen evaluation processes to cover a wider range of commercially available compounds?
A: Great question. Tools like QSAR (quantitative structure-activity relationships) and other AI- based approaches have helped with not only prioritization but also the evaluation process (which is very labor intensive and thus low throughput). A couple of recent publications: https://pubmed.ncbi.nlm.nih.gov/33984576/ , https://pubmed.ncbi.nlm.nih.gov/27164621/ but there is a lot of active work in this area.
Q: How do we keep "interested parties" (chemical companies) from funding studies and expecting non-harmful results on their chemicals because they funded it?
A: Good question - managing conflicts of interest is an important aspect of performing evaluations. Many systematic review processes consider the possible bias brought by funding source. Transparency about who funded a study, and the role of the sponsor, is very important when studies are published.
Q: Can you elaborate on how mechanistic (and other data)/rapid testing help--or is already helping--with the development of safer alternatives, e.g., green chemistry or products?
A: Great question. The IARC has a long history of using mechanistic data in cancer hazard evaluations - and there are a number of agents classified on the basis of mechanistic data alone (e.g., crotonaldehyde, a component of air pollution and tobacco smoke). There are opportunities for future development and increasing confidence in how these data can support evidence-based decision making.
Q: Could you share your opinion about exposure to mixtures of carcinogens.? In some places of the world the exposure is a low level of mixtures.
A: Great question. In some cases, there are exposures mixtures, but the levels aren’t necessarily low. We can think about areas with endemic aflatoxin B1 exposure, where there is also endemic hepatitis virus infection. AND heavy alcohol drinking… liver cancer rates may be as high as 1/10 in men in some parts of Asia, there is a compounding of risk from different factors that all affect liver cancer. It’s important to bear these lessons in mind when we think about community-level risk especially where there can other factors at play including limited access to health care.
Q: Why might pathogen caused have dropped 10%?
A: I think the attribution percentage changed because as more individuals are vaccinated with HPV vaccine, the percent caused by this virus will go down.
Q: You may touch on this upcoming, but do you think public education and increased recommendation of mammography and other routine screening tests cause us to see more cancers?
A: This can contribute to trends among older age groups that are screened but doesn't explain increases in younger age groups.
Q: Could endogenous factors associated with aging make older adults more susceptible to environmental carcinogens?
A: Yes, it can, but likely depends on the cancer type.
Q: Shouldn't we just get rid of the pie that adds up to 100% attributable risk?
A: I agree, Dr. Schettler. A pie chart is not a useful way to show attributable risks since they are expected to add to more than 100% and can't reflect the many interactions between exposures and susceptibility.
Q: Even when the carcinogenicity of a substance or other agent has been determined, it has not necessarily led to any government action to prevent its use, production, or environmental exposures. What is or should be the role of scientists and public health professionals in correcting this regulatory laxity?
A: Great question. I think about it as everyone having a role to play. I think Dr. Terry put it very well, scientists build trust through transparency and being honest about where there is certainty and where there isn’t.
Q: There are some risk factors that can be easily measured. However, there are carcinogens that people are exposed to that they are not aware of, nor are their health care providers. How we can be aware of exposure to carcinogens?
A: This will depend on the type of chemical exposures - there are apps now to understand what chemicals are in cleaning products and personal care products - there are also kits to get an individual’s own levels - some of this is on the Silent Spring Institute website.
Q: Dr. Guyton talked about a 2009 paper that referred to the upstream causes of cancers. How has that organization/categorization of cancers affected how we look at cancer clusters where there are cancers of different types, especially in smaller communities that are concerned about chemical exposures? Can you direct us to resources that would support this type of changed perspective on cancer cluster studies?
A: Thanks for this great question. The 2009 paper sparked a lot of good thinking and this was really taken forward in the key characteristics concept that I mentioned. There are opportunities for future development and increasing confidence in how these data can support evidence-based decision making. Cancer cluster studies may be informed by the windows of exposure concept that Dr. Terry discussed. But also study of the community exposures and endpoints relevant to key characteristics in people who didn’t get cancer but are nonetheless at risk. I hope that helps.
Q: It would be very valuable for clinicians to collect occupational histories from their patients to capture potential toxic exposures.
A: Yes, it is very important for health providers to understand patient occupational exposures.
Q: How did the error in Wilmington occur and how are we preventing it from happening again? Was the Wilmington water not compliant? Was water not being measured for this substance? Or is the substance more carcinogenic than we thought?
A: I believe that several important contaminants were not being measured because there were not regulations requiring that.
Q: Please repeat the full name of the pediatric environmental health organization.
A: Part of CDC - they are called Pediatric Environmental Health Specialty Units (PEHSU).
Resources
The Massachusetts "Environmental Public Health Tracking Portal" (EHPHT)
Massachusetts Department of Public Health, 2021. MDPH Webpage for the Wilmington Childhood Cancer Study.
Massachusetts Department of Public Health, 2021. Clinicians’ Experience with Environmental Exposures.
The Story of Health – A Multimedia EBook. Produced by the Western States Pediatric Environmental Health Unit (PEHSU). Exploring how multiple environments influence our health across the lifespan