Background
There are many mechanisms by which carcinogens induce the transformation of a normal cell or tissue into a tumour cell or cancerous tissue. This production of knowledge is part of a temporality punctuated by hypotheses, available technologies, methodologies for obtaining evidence. The level of evidence required to reach a consensus and to be validated within the scientific community. However, more and more works underline the gap of knowledge between scientific and regulatory communities, as it was evidenced by the case of the pesticide glyphosate and the controversy between IARC and regulatory agencies.
In this work, we focused on how carcinogenicity mechanisms have been integrated into the process of assessing the carcinogenicity of pesticides over time, in particular genotoxicity and metabolic reprogramming, in the European regulatory framework. Our case studies are SDHI (succinate dehydrogenase inhibitors) pesticides, which target mitochondrial cellular respiration and energy metabolism.
Objectives
Our objectives are to understand how certain mechanisms have been included or excluded from carcinogenicity criteria, to analyse specific cases from SDHI pesticide regulatory dossiers, and to assess how the epistemic selectivity of carcinogenicity mechanisms affects pesticide marketing and public health.
Methods
We have combined approaches from the history of cancer science, the philosophy of cancer, science and technology studies, and toxicology. We have studied 15 regulatory dossiers for SDHI pesticides, in which we examined the toxicological results, the interpretations provided by the firm and the conclusions made by regulatory agencies.
Results
Our research shows that genotoxicity has played a dominant role as a mechanism of carcinogenesis in pesticide regulation since the 1980s. Conversely, metabolic reprogramming and, in particular, the Warburg effect, discovered in the 1950s, was only ‘revisited’ in the early 2000s. Analysis of the regulatory dossiers for SDHI pesticides shows that most of them are carcinogenic in rodents. However, the carcinogenicity mechanisms taken into account in the assessment focus on genotoxicity, and no interpretation mentions metabolic reprogramming as a model of carcinogenesis. This epistemic selectivity leads to the authorisation of carcinogenic pesticides for sale.
Conclusion/implications
Pesticides targeting mitochondria and energy metabolism constitute a significant share of the market. The exclusion of carcinogenicity models from regulatory procedures can have significant consequences for public health.