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Evaluation of the herbicide glyphosate, (aminomethyl)phosphonic acid, and glyphosate-based formulations for genotoxic activity using in vitro assays

Stephanie L. Smith-Roe, Carol D. Swartz, Asma Rashid, Nicholas C. Christy, Jamie E. Sly, Xiaoqing Chang, Nisha S. Sipes, Keith R. Shockley, Shawn F. Harris, Sandra J. McBride, Gary J. Larson, Bradley J. Collins, Esra Mutlu, Kristine L. Witt

Environmental and Molecular Mutagenesis: https://onlinelibrary.wiley.com/doi/10.1002/em.22534
DOI: https://doi.org/10.22427/NTP-DATA-002-02220-0014-0000-3

Two data values for one concentration in the 4 h +S9 experimental condition were corrected after a quality assurance audit. This finding did not impact the interpretation of the study.



Glyphosate, the most heavily used herbicide world-wide, is applied to plants in complex formulations that promote absorption. The National Toxicology Program reported in 1992 that glyphosate, administered to rats and mice at doses up to 50,000 ppm in feed for 13 weeks, showed little evidence of toxicity, and no induction of micronuclei was observed in the mice in this study. Subsequently, mechanistic studies of glyphosate and glyphosate-based formulations (GBFs) that have focused on DNA damage and oxidative stress suggest that glyphosate may have genotoxic potential. However, few of these studies directly compared glyphosate to GBFs, or effects among GBFs. To address these data gaps, we tested glyphosate, glyphosate isopropylamine (IPA), and (aminomethyl)phosphonic acid (AMPA, a microbial metabolite of glyphosate), 9 high-use agricultural GBFs, 4 residential-use GBFs, and additional herbicides (metolachlor, mesotrione, and diquat dibromide) present in some of the GBFs in bacterial mutagenicity tests, and in human TK6 cells using a micronucleus assay and a multiplexed DNA damage assay. Our results showed no genotoxicity or notable cytotoxicity for glyphosate or AMPA at concentrations up to 10 mM, while all GBFs and herbicides other than glyphosate were cytotoxic, and some showed genotoxic activity. An in vitro to in vivo extrapolation of results for glyphosate suggest that it is of low toxicological concern for humans. In conclusion, these results demonstrate a lack of genotoxicity for glyphosate, consistent with observations in the NTP in vivo study, and suggest that toxicity associated with GBFs may be related to other components of these formulations.

Supplemental Materials

Supplemental Data



We thank the following individuals for their essential contributions to data management and integration for this study: Jennifer Fostel, PhD, DNTP Office of Data Science; From the Arctic Slope Regional Corporation (ASRC) Federal Vistronix: Julie Berke, BS; Erik Diffin, BS; Shihan He, PhD, Marcus Jackson, BS; Amber Macpherson, BS; Nicole Sayers*, BS; Vicky Youn**, MS. *Presently at DLH Corporation **Presently at Research Triangle Institute (RTI) International

Genetic Toxicology

(Aminomethyl)phosphonic acid

Buccaneer Plus

Cornerstone Plus

Diquat dibromide Monohydrate

Durango DMA


Glyphosate Isopropylamine Salt

Glystar Plus

Halex GT




Remuda Full Strength

Roundup Concentrate Plus

Roundup Custom

Roundup PowerMAX

Roundup Super Concentrate

Roundup WeatherMAX

Touchdown Total