J Korean Med Sci.  2012 Jul;27(7):711-715. 10.3346/jkms.2012.27.7.711.

In Vitro Cytotoxic Effect of Glyphosate Mixture Containing Surfactants

Affiliations
  • 1Department of Immunology, Soonchunhyang University College of Medicine, Cheonan, Korea.
  • 2Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea. syhong@sch.ac.kr

Abstract

We investigated whether glyphosate influences the cellular toxicity of the surfactants TN-20 and LN-10 on the mouse fibroblast-like cells, alveolar epithelial cells, and a heart cell line. The cytotoxicity of TN-20 and LN-10 (0.4-100 microM), in the presence or absence of glyphosate was determined by assessing membrane integrity. TN-20 toxicity was significantly lower in the presence of 50 microM glyphosate for the fibroblast-like cell (6.25 microM; 3.9% +/- 3.4% vs -4.8% +/- 0.7%), for the alveolar cells (0.78 microM; 5.7% +/- 0.9% vs 0.1% +/- 0.6%), and for the heart cell line (25.0 microM; 7.9% +/- 3.0% vs 19.4% +/- 0.7%) compared to that of TN-20 alone. The cellular toxicity of LN-10 towards the fibroblast-like cells was found to be increased in the presence of 50 microM glyphosate when LN-10 concentrations of 50 microM (31.3% +/- 3.9% vs 19.2% +/- 0.9%) and 100 microM (62.1% +/- 3.4% vs 39.0% +/- 0.7%) were compared to that of LN-10 alone. These results suggest that the mixture toxicity may be a factor in glyphosate-surfactant toxicity in patients with acute glyphosate herbicide intoxication.

Keyword

Glyphosate; Surfactants; Complex Mixtures; Toxicity; Herbicides

MeSH Terms

Animals
Cell Line
Cell Survival/drug effects
Glycine/*analogs & derivatives/chemistry/toxicity
Herbicides/chemistry/*toxicity
Mice
Polyethylene Glycols/*chemistry
Surface-Active Agents/*chemistry
Herbicides
Polyethylene Glycols
Surface-Active Agents
Glycine

Figure

  • Fig. 1 The cytotoxicity of glyphosate, TN-20, and LN-10. Cytotoxicity was determined by assessing the number of metabolically active (A) fibroblast, (B) alveolar, and (C) heart cells using an MTT assay. Cells were cultured with various concentrations of glyphosate, TN-20, and LN-10, ranging from 0 to 100 µM. The cytotoxicity of TN-20 and LN-10 is found to be dose dependent in all the 3 cell lines, whereas no cellular toxicity due to any concentration of glyphosate is observed.

  • Fig. 2 The cellular toxicity of TN-20 in the presence or absence of glyphosate. (A) LDH assays examining the toxicity of TN-20 in fibroblast-like cells revealed that there was significantly lower toxicity in the mixtures of 50 µM glyphosate and 6.25, 12.5, 25, and 100 µM TN-20. No significant differences in the cellular toxicity of TN-20 in the presence or absence of 100 µM of glyphosate were observed. (B) The cellular toxicity of TN-20 toward alveolar cells is lower when TN-20 was mixed with 50 µM of glyphosate at concentrations of 0.78, 1.56, 3.13, 6.25, 12.5, 25, 50, and 100 µM. It is also lower when TN-20 was mixed with 100 µM of glyphosate at concentrations of 12.5, 25, 50, and 100 µM. (C) In heart cells, the cellular toxicity of TN-20 is greater when mixed with 50 µM of glyphosate at concentrations of 25 and 50 µM, as well as when TN-20 was mixed with 100 µM of glyphosate at concentrations of 25, 50, and 100 µM.

  • Fig. 3 Cellular toxicity of LN-10 in the presence or absence of glyphosate. (A) LDH assays examining the toxicity of TN-20 in the fibroblast-like cells revealed that there was significantly greater toxicity in the mixtures containing 50 µM glyphosate and 50 µM and 100 µM LN-10 than LN-10 alone. The cellular toxicity of LN-10 is also greater in a mixture of 100 µM of both LN-10 and glyphosate. (B) In alveolar cells, no significant difference in the cellular toxicity of LN-10, with or without glyphosate is observed. (C) The cellular toxicity of LN-10 toward heart cells is greater than LN-10 alone when mixed with 100 µM of glyphosate at concentrations of 1.56, 3.13, 6.25, and 12.5 µM, although no significant differences in cellular toxicity were observed when LN-10 was mixed with 50 µM of glyphosate.


Reference

1. Chen YJ, Wu ML, Deng JF, Yang CC. The epidemiology of glyphosate-surfactant herbicide poisoning in Taiwan, 1986-2007: a poison center study. Clin Toxicol (Phila). 2009. 47:670–677.
2. Roberts DM, Buckley NA, Mohamed F, Eddleston M, Goldstein DA, Mehrsheikh A, Bleeke MS, Dawson AH. A prospective observational study of the clinical toxicology of glyphosate-containing herbicides in adults with acute self-poisoning. Clin Toxicol (Phila). 2010. 48:129–136.
3. Bradberry SM, Proudfoot AT, Vale JA. Glyphosate poisoning. Toxicol Rev. 2004. 23:159–167.
4. Moon JM, Chun BJ. Predicting acute complicated glyphosate intoxication in the emergency department. Clin Toxicol (Phila). 2010. 48:718–724.
5. Sawada Y, Nagai Y, Ueyama M, Yamamoto I. Probable toxicity of surface-active agent in commercial herbicide containing glyphosate. Lancet. 1988. 1:299.
6. Seok SJ, Park JS, Hong JR, Gil HW, Yang JO, Lee EY, Song HY, Hong SY. Surfactant volume is an essential element in human toxicity in acute glyphosate herbicide intoxication. Clin Toxicol (Phila). 2011. 49:892–899.
7. Lee HL, Kan CD, Tsai CL, Liou MJ, Guo HR. Comparative effects of the formulation of glyphosate-surfactant herbicides on hemodynamics in swine. Clin Toxicol (Phila). 2009. 47:651–658.
8. Tai T, Yamashita M, Wakimori H. Hemodynamic effects of Roundup, glyphosate and surfactant in dogs. Jpn J Toxicol. 1990. 3:63–68.
9. Baeurle SA, Kroener J. Modeling effective interactions of micellar aggregates of ionic surfactants with the Gauss-core potential. J Math Chem. 2004. 36:409–421.
10. Hermens J, Canton H, Janssen P, De Jong R. Quantitative structure-activity relationships and toxicity studies of mixtures of chemicals with anaesthetic potency: acute lethal and sublethal toxicity to Daphnia magna. Aquat Toxicol. 1984. 5:143–154.
11. Junghans M, Backhaus T, Faust M, Scholze M, Grimme L. Application and validation of approaches for the predictive hazard assessment of realistic pesticide mixtures. Aquat Toxicol. 2006. 76:93–110.
12. Deneer JW. Toxicity of mixtures of pesticides in aquatic systems. Pest Manag Sci. 2000. 56:516–520.
13. Song HY, Kim YH, Seok SJ, Gil HW, Yang JO, Lee EY, Hong SY. Cellular toxicity of surfactants used as herbicide additives. J Korean Med Sci. 2012. 27:3–9.
14. Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE. Differential effects of glyphosate and roundup on human placental cells and aromatase. Environ Health Perspect. 2005. 113:716–720.
15. Phoa FK, Xu H, Wong WK. The use of nonregular fractional factorial designs in combination toxicity studies. Food Chem Toxicol. 2009. 47:2183–2188.
16. Brown VM. The calculation of the acute toxicity of mixtures of poisons to rainbow trout. Water Res. 1968. 2:723–733.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr