Carcinogenic effects of long-term exposure from prenatal life to glyphosate and glyphosate-based herbicides in Sprague–Dawley rats
Simona Panzacchi, Eva Tibaldi, Luana De Angelis, Laura Falcioni, Rita Giovannini, Federica Gnudi, Martina Iuliani, Marco Manservigi, Fabiana Manservisi, Isabella Manzoli, Ilaria Menghetti, Rita Montella, Roberta Noferini, Daria Sgargi, Valentina Strollo, Francesca Truzzi, Michael Antoniou, Jia Chen, Giovanni Dinelli, Stefano Lorenzetti, Alberto Mantovani, Robin Mesnage, Melissa J. Perry, Andrea Vornoli, Philip J. Landrigan, Fiorella Belpoggi, Daniele Mandrioli
Abstract
BACKGROUND: Glyphosate-based herbicides (GBHs) are the world's most widely used weed control agents. Public health concerns have increased since the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen in 2015. To further investigate the health effects of glyphosate and GBHs, the Ramazzini Institute launched the Global Glyphosate Study (GGS), which is designed to test a wide range of toxicological outcomes. Reported here are the results of the carcinogenicity arm of the GGS. METHODS: Glyphosate and two GBHs, Roundup Bioflow used in the European Union (EU) and RangerPro used in the U.S., were administered to male and female Sprague-Dawley (SD) rats, beginning at gestational day 6 (via maternal exposure) through 104 weeks of age. Glyphosate was administered through drinking water at three doses: the EU acceptable daily intake (ADI) of 0.5 mg/kg body weight/day, 5 mg/kg body weight/day and the EU no-observed adverse effect level (NOAEL) of 50 mg/kg body weight/day. The two GBH formulations were administered at the same glyphosate-equivalent doses. RESULTS: In all 3 treatment groups, statistically significant dose-related increased trends or increased incidences of benign and malignant tumors at multiple anatomic sites were observed compared to historical and concurrent controls. These tumors arose in haemolymphoreticular tissues (leukemia), skin, liver, thyroid, nervous system, ovary, mammary gland, adrenal glands, kidney, urinary bladder, bone, endocrine pancreas, uterus and spleen (hemangiosarcoma). Increased incidences occurred in both sexes. Most of these involved tumors that are rare in SD rats (background incidence < 1%) with 40% of leukemias deaths in the treated groups occurring before 52 weeks of age and increased early deaths were also observed for other solid tumors. CONCLUSIONS: Glyphosate and GBHs at exposure levels corresponding to the EU ADI and the EU NOAEL caused dose-related increases in incidence of multiple benign and malignant tumors in SD rats of both sexes. Early-life onset and mortality were observed for multiple tumors. These results provide robust evidence supporting IARC's conclusion that there is "sufficient evidence of carcinogenicity [of glyphosate] in experimental animals". Furthermore, our data are consistent with epidemiological evidence on the carcinogenicity of glyphosate and GBHs.