Leukemia in Sprague-Dawley Rats Exposed Long-term from Prenatal Life to Glyphosate and Glyphosate-Based Herbicides

Panzacchi, S.; Tibaldi, E.; De Angelis, L.; Falcioni, L.; Gnudi, F.; Iuliani, M.; Manservigi, M.; Manservisi, F.; Manzoli, I.; Menghetti, I.; Montella, R.; Noferini, R.; Sgargi, D.; Strollo, V.; Antoniou, M.; Chen, J.; Dinelli, G.; Lorenzetti, S.; Mesnage, R.; Vornoli, A.; Perry, M. J.; Landrigan, P. J.; Belpoggi, F.; Mandrioli, D.

doi:10.1101/2023.11.14.566013

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bioRxiv · 10.1101/2023.11.14.566013

Leukemia in Sprague-Dawley Rats Exposed Long-term from Prenatal Life to Glyphosate and Glyphosate-Based Herbicides

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Abstract

BackgroundGlyphosate-based herbicides (GBHs) are the worlds most widely used weed control agents. There has been intense and increasing public health concern about glyphosate and GBHs since the International Agency for Research on Cancer classified glyphosate as a probable human carcinogen in 2015. AimsTo further study the health effects of glyphosate and GBHs, the Ramazzini Institute, in collaboration with an international network of institutes and universities, has launched the Global Glyphosate Study (GGS), the most comprehensive toxicological study ever performed on these compounds. The GGS is an integrated study designed to test a wide range of toxicological outcomes including carcinogenicity, neurotoxicity, multi-generational effects, organ toxicity, endocrine disruption and prenatal developmental toxicity. The present study reports the first definitive results on leukemia incidence and mortality from the carcinogenicity arm of the GGS. MethodGlyphosate and two GBHs, Roundup Bioflow (MON 52276) used in the European Union (EU) and RangerPro (EPA 524-517) used in the U.S., were administered long-term to Sprague-Dawley (SD) rats beginning in prenatal life until 104 weeks of age via drinking water at doses of 0.5, 5, and 50 mg/kg body weight/day. This dose range encompasses both the EU Acceptable Daily Intake (ADI) and the EU No Observed Adverse Effect Level (NOAEL) for glyphosate. Each experimental group was composed of 51 males and 51 females, the total number animals were 1020 (510 males and 510 females). ResultsIn the animals exposed to glyphosate, a significantly increased trend in incidence of lymphoblastic leukemia was observed in males. In the Roundup Bioflow-treated animals, significantly increased trends were observed in incidence of lymphoblastic leukemia (males and females), monocytic leukemia (males), total myeloid leukemia (males), and all leukemias combined (males and females). In the RangerPro-treated animals, significantly increased trends were observed in incidence of lymphoblastic leukemia (males and females), monocytic leukemia (males) and all leukemias combined (males). 43% of leukemias deaths in the glyphosate and GBHs treated groups occurred before the first year of age (52 weeks). ConclusionsGlyphosate and GBHs at exposure levels corresponding to the EU ADI and the EU NOAEL caused significant, dose-related increased trends in incidence of leukemia, a very rare malignancy, in SD rats. Notably, about half of the leukemia deaths seen in the glyphosate and GBH groups occurred at less than one year of age, comparable to less than 35-40 years of age in humans.

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Panzacchi, S., Tibaldi, E., De Angelis, L., Falcioni, L., Gnudi, F., Iuliani, M., Manservigi, M., Manservisi, F., Manzoli, I., Menghetti, I., Montella, R., Noferini, R., Sgargi, D., Strollo, V., Antoniou, M., Chen, J., Dinelli, G., Lorenzetti, S., Mesnage, R., Vornoli, A., Perry, M. J., Landrigan, P. J., Belpoggi, F., Mandrioli, D.. 2023-11-16. Leukemia in Sprague-Dawley Rats Exposed Long-term from Prenatal Life to Glyphosate and Glyphosate-Based Herbicides. https://doi.org/10.1101/2023.11.14.566013

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