TY - JOUR
T1 - The surfactant co-formulant POEA in the glyphosate-based herbicide RangerPro but not glyphosate alone causes necrosis in Caco-2 and HepG2 human cell lines and ER stress in the ToxTracker assay
AU - Mesnage, Robin
AU - Ferguson, Scarlett
AU - Brandsma, Inger
AU - Moelijker, Nynke
AU - Zhang, Gaonan
AU - Mazzacuva, Francesca
AU - Caldwell, Anna
AU - Halket, John
AU - Antoniou, Michael N.
N1 - Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robin Mesnage is supported by a grant to Michael Antoniou from the Sustainable Food Alliance (USA) . Inger Brandsma, Nynke Moelijker and Gaonan Zhang are employees of Toxys. Robin Mesnage acts in an expert consulting or advisory capacity with a law firm involved in litigation in the US over glyphosate/Roundup health effects.
Publisher Copyright:
© 2022 The Authors
PY - 2022/10
Y1 - 2022/10
N2 - The toxicity of co-formulants present in glyphosate-based herbicides (GBHs) has been widely discussed leading to the European Union banning the polyoxyethylene tallow amine (POEA). We identified the most commonly used POEA, known as POE-15 tallow amine (POE-15), in the widely used US GBH RangerPro. Cytotoxicity assays using human intestinal epithelial Caco-2 and hepatocyte HepG2 cell lines showed that RangerPro and POE-15 are far more cytotoxic than glyphosate alone. RangerPro and POE-15 but not glyphosate caused cell necrosis in both cell lines, and that glyphosate and RangerPro but not POE-15 caused oxidative stress in HepG2 cells. We further tested these pesticide ingredients in the ToxTracker assay, a system used to evaluate a compound's carcinogenic potential, to assess their capability for inducing DNA damage, oxidative stress and an unfolded protein response (endoplasmic reticulum, ER stress). RangerPro and POE-15 but not glyphosate gave rise to ER stress. We conclude that the toxicity resulting from RangerPro exposure is thus multifactorial involving ER stress caused by POE-15 along with oxidative stress caused by glyphosate. Our observations reinforce the need to test both co-formulants and active ingredients of commercial pesticides to inform the enactment of more appropriate regulation and thus better public and environmental protection.
AB - The toxicity of co-formulants present in glyphosate-based herbicides (GBHs) has been widely discussed leading to the European Union banning the polyoxyethylene tallow amine (POEA). We identified the most commonly used POEA, known as POE-15 tallow amine (POE-15), in the widely used US GBH RangerPro. Cytotoxicity assays using human intestinal epithelial Caco-2 and hepatocyte HepG2 cell lines showed that RangerPro and POE-15 are far more cytotoxic than glyphosate alone. RangerPro and POE-15 but not glyphosate caused cell necrosis in both cell lines, and that glyphosate and RangerPro but not POE-15 caused oxidative stress in HepG2 cells. We further tested these pesticide ingredients in the ToxTracker assay, a system used to evaluate a compound's carcinogenic potential, to assess their capability for inducing DNA damage, oxidative stress and an unfolded protein response (endoplasmic reticulum, ER stress). RangerPro and POE-15 but not glyphosate gave rise to ER stress. We conclude that the toxicity resulting from RangerPro exposure is thus multifactorial involving ER stress caused by POE-15 along with oxidative stress caused by glyphosate. Our observations reinforce the need to test both co-formulants and active ingredients of commercial pesticides to inform the enactment of more appropriate regulation and thus better public and environmental protection.
UR - http://www.scopus.com/inward/record.url?scp=85137298422&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2022.113380
DO - 10.1016/j.fct.2022.113380
M3 - Article
C2 - 36028061
AN - SCOPUS:85137298422
SN - 0278-6915
VL - 168
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
M1 - 113380
ER -