Last month, the International Agency for Research on Cancer (IARC) announced its new classification for "automotive gasoline and some oxygenated gasoline additives."1 In a result that follows IARC's previous pattern and practice and that the authors of this update forecasted last year,2 the IARC Working Group found gasoline to be a Group 1 "Carcinogenic" compound and found the gasoline additives MTBE and ETBE to be Group 2B "possibly carcinogenic" compounds.
What is IARC?
IARC is a branch of the World Health Organization (WHO) based in Lyon, France. Mandated by WHO to investigate potential causes of cancer, IARC conducts hazard evaluations of suspected carcinogens multiple times a year. The results of these evaluations are published in IARC "Monographs" — lengthy summary publications that discuss the existing literature and then apply a cancer classification based upon the Monograph Working Group evaluation. Under current IARC guidelines, it is impossible to classify any evaluated substance as "not carcinogenic" — the best the guidelines allow is "insufficient evidence to deem carcinogenic."3 Additionally, IARC Monograph Working Groups — with few exceptions — are only allowed to consider as part of their review published data in the peer-reviewed literature regarding substances or exposures they evaluate. In the case of regulated substances, where many safety studies are submitted to regulators but are not placed in the peer-reviewed literature, this can create a situation where IARC Working Groups only review a subset of the available data on a given compound or exposure, potentially leading to erroneous conclusions based on incomplete data sets.
IARC and Litigation
IARC evaluations have been an issue in litigation for decades, starting first with the earlier iterations of asbestos cases in the 1980s and 1990s. In recent years, IARC evaluations of the chemical aspartame (found in Diet Coke) and perfluorinated chemicals have garnered widespread attention.4 Earlier IARC evaluations of the active ingredient in the pesticide Roundup (glyphosate), the active ingredient in the pharmaceutical drug Actos (pioglitazone), polychlorinated biphenyls (PCBs), and benzene either spurred or rekindled personal injury litigation surrounding those compounds.
In addition to inciting personal injury litigation, an IARC classification of "carcinogenic" (Group 1) or "probably carcinogenic" (Group 2A) results in automatic listing as carcinogenic under California's Proposition 65 law. Under Proposition 65, bounties are available to private citizens or organizations who bring lawsuits claiming products contain levels of listed carcinogens that exceed the state's safe harbor level. These Proposition 65 lawsuits have been brought alleging undisclosed carcinogens in products like coffee and French fries.5
Some courts have expressed a healthy skepticism of IARC classifications.6 Despite that skepticism, IARC classifications continue to spur litigation time and time again, and most courts still allow the findings of IARC Working Groups to provide bases for claims against corporate defendants in a wide variety of cases.
Was the IARC Working Group for Gasoline Independent?
IARC claims to maintain a strict conflict of interest policy, but unfortunately, this has been applied inconsistently to the makeup of their Working Groups in the past. For instance, IARC has previously allowed expert witnesses in litigation for plaintiffs to serve on working groups examining exposures about which they're testifying while excluding from participation individuals with ties to companies producing the exposures.7
In the case of IARC Working Group 138, the makeup of the group suggested a lack of balance in viewpoints. For instance, an epidemiologist named Julia Heck was included on the Working Group. She had previously published on traffic pollution and byproducts of gasoline – arguing that exposure to those byproducts is associated with childhood leukemia and breast cancer.8 Likewise, a scientist named Sunisa Chaiklieng was a member of the Working Group. She had previously published on research claiming gasoline station workers were at an increased risk of all cancer.9 Apparently, no researchers were included on the Working Group who had opined gasoline exposure or byproduct exposure did not lead to an increased risk of cancer.
Given IARC's disparate treatment of conflicts of interest in the past, it is unsurprising that Working Group 138 lacked a balance of viewpoints. This lack of balance often leads to classifications that do not reflect scientific consensus. Over the past decade, IARC classifications for a multitude of chemicals have been criticized by regulatory authorities as out-of-step with the scientific data.10
In the case of gasoline and MTBE, IARC's classification is again out of step with the scientific consensus. EPA has determined that the epidemiologic evidence to classify gasoline as carcinogenic is "inadequate"11 and the ATSDR noted at its last review that extant epidemiology studies had "inherent limitations that preclude[d] their use as evidence for an association between gasoline exposure and cancer."12 Likewise, the National Toxicology Program reviewed the carcinogenicity of MTBE in 1998 and determined at that time that rodent data was insufficient to classify MTBE as carcinogenic.13
What To Do Next?
Industries and parties affected by the IARC review should consider starting to educate the public and relevant regulatory and political bodies about what goes into an IARC classification. Specifically, the public and relevant bodies should be aware that IARC often relies upon incomplete data as the policies under which Working Groups operate do not allow for the review of data not in the peer-reviewed literature or publicly released by regulatory agencies. Thus, in many cases, IARC Working Groups do not consider many of the regulatory guideline studies necessary for product registration and use in the US and elsewhere.
Additionally, interested parties should be aware than an IARC evaluation is a "closed" analysis – no peer review or public comment is permitted and no transcript is kept of the meeting or its deliberations. Shrouded in secrecy, exposing flaws in IARC's process can be difficult after-the-fact. The public and relevant bodies should be informed that an IARC evaluation is a hazard assessment – in other words, it is a determination that a substance might be carcinogenic at some dose, but it does not address whether the dose people are exposed to in their daily lives could cause cancer.
Finally, affected parties should prepare for litigation – both of the Proposition 65 and personal injury variety. IARC Working Group assessments have been used by the plaintiffs' bar to prop up litigation for decades and for a product as ubiquitous as gasoline, it is expected that some litigation will result from the classification.
Footnotes
3. See IARC Update Frustrates Industry and NGOs, Chemical Watch, May 2, 2019 (discussing removal of "probably not carcinogenic to humans" classification from IARC preamble). https://chemicalwatch.com/77053/iarc-update-frustrates-industry-and-ngos .
4. See, e.g., Does Aspartame Cause Cancer? It's Complicated, Chemical and Engineering News (April 28, 2024) (discussing aspartame classification and regulatory response). https://cen.acs.org/food/food-ingredients/Does-aspartame-cause-cancer-s/102/i13.
5. See The Secretive Non-Profit Gaming California's Health Laws, The Outline (June 18, 2018) (discussing Proposition 65 lawsuits). https://theoutline.com/post/4963/council-education-research-toxics-california-coffee-lawsuit-cancer-label .
6. See Nat'l Ass'n of Wheat Growers v. Bonta, 85 F.4th 1263, 1278 (9th Cir. 2023) ("IARC stands essentially alone in its determination that glyphosate is probably carcinogenic to humans, while EPA, OEHHA, and regulators from around the world conclude that it is not.").
7. See, e.g. Newman v. Motorola, 78 F. App'x 292, 293-94 (4th Cir. 2003) (discussing expert testimony of Lennart Hardell — a later participant in IARC Working Group on RF Electromagnetic Fields) and https://www.reuters.com/article/us-health-who-iarc-special-report-idUSKCN0XF0RF (discussing exclusion from same working group of Anders Ahlbom).
8. See A review and meta-analysis of outdoor air pollution and risk of childhood leukemia - PubMed; Exposure to outdoor ambient air toxics and risk of breast cancer: The multiethnic cohort - PubMed.
9. See Risk Assessment on Benzene Exposure among Gasoline Station Workers - PubMed.
10. See Aspartame and Other Sweeteners in Food | FDA (discussing FDA disagreement with IARC as to aspartame); Glyphosate | US EPA (discussing EPA disagreement with IARC as to glyphosate).
11. See Document Display | NEPIS | US EPA (but note EPA did find gasoline was carcinogenic in rodent models).
12. ATSDR Gasoline Tox Profile (cdc.gov).
13. RoC Background Document: Methyl tertiary-Butyl Ether; Dec. 2-3, 1998 (nih.gov); Appendix C; 15th RoC 2021 (nih.gov).
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
