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

Mesnage, Robin; Ferguson, Scarlett; Brandsma, Inger; Moelijker, Nynke; Zhang, Gaonan; Mazzacuva, Francesca; Caldwell, A. G.; Halket, John M.; Antoniou, Michael

doi:10.1016/j.fct.2022.113380

Cited by 21 publications

(13 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously shown that Roundup Bioflow, which does not contain POEA but a quaternary ammonium surfactant ( Mesnage et al, 2021a ) causes more gut microbiome alterations than glyphosate alone in rats ( Mesnage et al, 2021b ). Although studies have described the presence of POEA surfactants in RangerPro ( Mesnage et al, 2022b ), the complete co-formulant profile remains unknown. Further studies testing the surfactants alone will be required to understand if they can be a source of effects in the absence of glyphosate.…”

Section: Discussionmentioning

confidence: 99%

“…Glyphosate and two commercial formulations, namely the EU representative formulation Roundup BioFlow (MON 52276) and the US formulation RangerPro (EPA 524-517), were again administered to Sprague–Dawley rats starting mid-gestation via drinking water at 0.5, 5, and 50 mg/kg bw/day, which ranged from the EU acceptable daily intake (ADI) to the EU no observed adverse effect level (NOAEL). RangerPro contains POEA surfactants ( Mesnage et al, 2022b ), while Roundup Bioflow does not contain POEA ( Mesnage et al, 2021a ), however the complete co-formulant profile remains unknown. Reported here are the effects of these three compounds on the caecum microbiota.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome

et al. 2022

Self Cite

View full text Add to dashboard Cite

The potential health consequences of glyphosate-induced gut microbiome alterations have become a matter of intense debate. As part of a multifaceted study investigating toxicity, carcinogenicity and multigenerational effects of glyphosate and its commercial herbicide formulations, we assessed changes in bacterial and fungal populations in the caecum microbiota of rats exposed prenatally until adulthood (13 weeks after weaning) to three doses of glyphosate (0.5, 5, 50 mg/kg body weight/day), or to the formulated herbicide products Roundup Bioflow and RangerPro at the same glyphosate-equivalent doses. Caecum bacterial microbiota were evaluated by 16S rRNA sequencing whilst the fungal population was determined by ITS2 amplicon sequencing. Results showed that both fungal and bacterial diversity were affected by the Roundup formulations in a dose-dependent manner, whilst glyphosate alone significantly altered only bacterial diversity. At taxa level, a reduction in Bacteroidota abundance, marked by alterations in the levels of Alloprevotella, Prevotella and Prevotellaceae UCG-003, was concomitant to increased levels of Firmicutes (e.g., Romboutsia, Dubosiella, Eubacterium brachy group or Christensenellaceae) and Actinobacteria (e.g., Enterorhabdus, Adlercreutzia, or Asaccharobacter). Treponema and Mycoplasma also had their levels reduced by the pesticide treatments. Analysis of fungal composition indicated that the abundance of the rat gut commensal Ascomycota Kazachstania was reduced while the abundance of Gibberella, Penicillium, Claviceps, Cornuvesica, Candida, Trichoderma and Sarocladium were increased by exposure to the Roundup formulations, but not to glyphosate. Altogether, our data suggest that glyphosate and its Roundup RangerPro and Bioflow caused profound changes in caecum microbiome composition by affecting the fitness of major commensals, which in turn reduced competition and allowed opportunistic fungi to grow in the gut, in particular in animals exposed to the herbicide formulations. This further indicates that changes in gut microbiome composition might influence the long-term toxicity, carcinogenicity and multigenerational effects of glyphosate-based herbicides.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The toxic effects and endocrine disrupting properties of the formulations were mostly due to the formulants and not to G[lyphosphate]” [ 44 ]. Another study concluded that the extensively used GBH RangerPro containing POEA (POE-15) was far more cytotoxic than glyphosate [ 46 ]. Nevertheless, the PMRA ignores independent scientific literature on the harmful effects of GBH formulations.…”

Section: Canadian Pesticide Evaluation and Regulation: Deficient And ...mentioning

confidence: 99%

Poisoning Regulation, Research, Health, and the Environment: The Glyphosate-Based Herbicides Case in Canada

Bacon

Vandelac

Gagnon

et al. 2023

Toxics

View full text Add to dashboard Cite

Despite discourse advocating pesticide reduction, there has been an exponential increase in pesticide use worldwide in the agricultural sector over the last 30 years. Glyphosate-Based Herbicides (GBHs) are the most widely used pesticides on the planet as well as in Canada, where a total of almost 470 million kilograms of declared “active” ingredient glyphosate was sold between 2007 and 2018. GBHs accounted for 58% of pesticides used in the agriculture sector in Canada in 2017. While the independent scientific literature on the harmful health and environmental impacts of pesticides such as GBHs is overwhelming, Canada has only banned 32 “active” pesticide ingredients out of 531 banned in 168 countries, and reapproved GBHs in 2017 until 2032. This article, based on interdisciplinary and intersectoral research, will analyze how as a result of the scientific and regulatory captures of relevant Canadian agencies by the pesticide industry, the Canadian regulation and scientific assessment of pesticides are deficient and lagging behind other countries, using the GBH case as a basis for analysis. It will show how, by embracing industry narratives and biased evidence, by being receptive to industry demands, and by opaque decision making and lack of transparency, Health Canada’s Pest Management Regulatory Agency (PMRA) promotes commercial interests over the imperatives of public health and environmental protection.

show abstract

“…This dose range encompasses both the EU acceptable daily intake (ADI) and the EU no-observed-adverse-effect level (NOAEL) for glyphosate. RangerPro contains POEA surfactants (Robin Mesnage et al 2022), while Roundup Bioflow does not contain POEA (Mesnage et al 2021b), however the complete co-formulant profile remains unknown. Evaluations of other neoplastic lesions from the carcinogenicity arm of the GGS are currently ongoing.…”

Section: Introductionmentioning

confidence: 99%

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

Panzacchi,

Tibaldi,

De Angelis

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundGlyphosate-based herbicides (GBHs) are the world’s 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.

show abstract

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

Cited by 21 publications

References 30 publications

Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome

Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome

Poisoning Regulation, Research, Health, and the Environment: The Glyphosate-Based Herbicides Case in Canada

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

Contact Info

Product

Resources

About