Advertisement

Toxicological Reviews

, Volume 23, Issue 3, pp 159–167 | Cite as

Glyphosate Poisoning

  • Sally M. Bradberry
  • Alex T. Proudfoot
  • J. Allister Vale
Review Article

Abstract

Glyphosate is used extensively as a non-selective herbicide by both professional applicators and consumers and its use is likely to increase further as it is one of the first herbicides against which crops have been genetically modified to increase their tolerance. Commercial glyphosate-based formulations most commonly range from concentrates containing 41% or more glyphosate to 1% glyphosate formulations marketed for domestic use. They generally consist of an aqueous mixture of the isopropylamine (IPA) salt of glyphosate, a surfactant, and various minor components including anti-foaming and colour agents, biocides and inorganic ions to produce pH adjustment.

The mechanisms of toxicity of glyphosate formulations are complicated. Not only is glyphosate used as five different salts but commercial formulations of it contain surfactants, which vary in nature and concentration. As a result, human poisoning with this herbicide is not with the active ingredient alone but with complex and variable mixtures. Therefore, It is difficult to separate the toxicity of glyphosate from that of the formulation as a whole or to determine the contribution of surfactants to overall toxicity. Experimental studies suggest that the toxicity of the surfactant, polyoxyethyleneamine (POEA), is greater than the toxicity of glyphosate alone and commercial formulations alone. There is insufficient evidence to conclude that glyphosate preparations containing POEA are more toxic than those containing alternative surfactants. Although surfactants probably contribute to the acute toxicity of glyphosate formulations, the weight of evidence is against surfactants potentiating the toxicity of glyphosate.

Accidental ingestion of glyphosate formulations is generally associated with only mild, transient, gastrointestinal features. Most reported cases have followed the deliberate ingestion of the concentrated formulation of Roundup®1 (41% glyphosate as the IPA salt and 15% POEA). There is a reasonable correlation between the amount ingested and the likelihood of serious systemic sequelae or death. Advancing age is also associated with a less favourable prognosis. Ingestion of >85mL of the concentrated formulation is likely to cause significant toxicity in adults. Gastrointestinal corrosive effects, with mouth, throat and epigastric pain and dysphagia are common. Renal and hepatic impairment are also frequent and usually reflect reduced organ perfusion. Respiratory distress, impaired consciousness, pulmonary oedema, infiltration on chest x-ray, shock, arrythmias, renal failure requiring haemodialysis, metabolic acidosis and hyperkalaemia may supervene in severe cases. Bradycardia and ventricular arrhythmias are often present pre-terminally. Dermal exposure to ready-to-use glyphosate formulations can cause irritation and photo-contact dermatitis has been reported occasionally; these effects are probably due to the preservative Proxel® (benzisothiazolin-3-one). Severe skin burns are very rare. Inhalation is a minor route of exposure but spray mist may cause oral or nasal discomfort, an unpleasant taste in the mouth, tingling and throat irritation. Eye exposure may lead to mild conjunctivitis, and superficial corneal injury is possible if irrigation is delayed or inadequate.

Management is symptomatic and supportive, and skin decontamination with soap and water after removal of contaminated clothing should be undertaken in cases of dermal exposure.

Keywords

Glyphosate Oral LD50 Spray Mist Glyphosate Formulation Systemic Sequela 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Goldstein DA, Acquavella JF, Mannion RM, et al. An analysis of glyphosate data from the California Environmental Protection Agency Pesticide Illness Surveillance Program. J Toxicol Clin Toxicol 2002; 40: 885–92PubMedCrossRefGoogle Scholar
  2. 2.
    Litovitz TL, Klein-Schwartz W, Rodgers Jr GC, et al. 2001 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2002; 20: 391–452PubMedCrossRefGoogle Scholar
  3. 3.
    Watson WA, Litovitz TL, Rodgers Jr GC, et al. 2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2003; 21: 353–421PubMedCrossRefGoogle Scholar
  4. 4.
    Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2004; 22: 335–404PubMedCrossRefGoogle Scholar
  5. 5.
    Lee H-L, Chen K-W, Chi C-H, et al. Clinical presentations and prognostic factors of a glyphosate-surfactant herbicide intoxication: a review of 131 cases. Acad Emerg Med 2000; 7: 906–10PubMedCrossRefGoogle Scholar
  6. 6.
    Talbot AR, Shiaw M-H, Huang J-S, et al. Acute poisoning with a glyphosate-surfactant herbicide (‘Round-up’): a review of 93 cases. Hum Exp Toxicol 1991; 10: 1–8PubMedCrossRefGoogle Scholar
  7. 7.
    Tominack RL, Yang G-Y, Tsai W-J, et al. Taiwan national poison center survey of glyphosate: surfactant herbicide ingestions. J Toxicol Clin Toxicol 1991; 29: 91–109PubMedCrossRefGoogle Scholar
  8. 8.
    Sawada Y, Nagai Y. Roundup® poisoning: its clinical observation: possible involvement of surfactant [in Japanese]. J Clin Exp Med 1987; 143: 25–7Google Scholar
  9. 9.
    Sawada Y, Nagai Y, Ueyama M, et al. Probable toxicity of surface-active agent in commercial herbicide containing glyphosate. Lancet 1988; I: 299CrossRefGoogle Scholar
  10. 10.
    Steinrücken HC, Amrhein N. The herbicide glyphosate is a potent inhibitor of 5-enolpyruvyl-shikimic acid-3-phosphate synthase. Biochem Biophys Res Commun 1980; 94: 1207–12PubMedCrossRefGoogle Scholar
  11. 11.
    Duke SO, Scheffler BE, Boyette D, et al. Herbicides, biotechnology for control of weeds. In: Plimmer JR, Gammon DW, Ragsdale NN. Encyclopedia of agrochemicals. Hoboken (NJ): Wiley-Interscience, 2003: 733–44Google Scholar
  12. 12.
    Sørensen FW, Gregersen M. Rapid lethal intoxication caused by the herbicide glyphosate-trimesium (Touchdown). Hum Exp Toxicol 1999; 18: 735–7PubMedCrossRefGoogle Scholar
  13. 13.
    International Programme on Chemical Safety. Environmental health criteria 159. Glyphosate. Geneva: World Health Organization, 1994Google Scholar
  14. 14.
    Olorunsogo OO, Bababunmi EA, Bassir O. Effect of glyphosate on rat liver mitochondria. Bull Environ Contam Toxicol 1979; 22: 357–64PubMedCrossRefGoogle Scholar
  15. 15.
    Olorunsogo OO, Bababunmi EA. Inhibition of succinate-linking reduction of pyridine nucleotide in rat liver mitochondria ‘in vivo’ by N-(phosphonomethyl) glycine. Toxicol Lett 1980; 7: 149–52PubMedCrossRefGoogle Scholar
  16. 16.
    Olorunsogo OO. Inhibition of energy-dependent transhydrogenase reaction by N-(phosphonomethyl)glycine in isolated rat liver mitochondria. Toxicol Lett 1982; 10: 91–5PubMedCrossRefGoogle Scholar
  17. 17.
    Bababunmi EA, Olorunsogo OO, Bassir O. The uncoupling effect of N-(phosphonomethyl) glycine on isolated rat liver mitochondria. Biochem Pharmacol 1979; 28: 925–7PubMedCrossRefGoogle Scholar
  18. 18.
    Hietanen E, Linnainmaa K, Vainio H. Effects of phenoxyherbicides and glyphosate on the hepatic and intestinal biotransformation activities in the rat. Acta Pharmacol Toxicol (Copenh) 1983 Aug; 53(2): 103–12CrossRefGoogle Scholar
  19. 19.
    El Demerdash FM, Yousef MI, Elagamy EI. Influence of paraquat, glyphosate, and cadmium on the activity of some serum enzymes and protein electrophoretic behavior (in vitro). J Environ Sci Health B 2001 Jan; 36(1): 29–42PubMedCrossRefGoogle Scholar
  20. 20.
    Williams GM, Kroes R, Munro IC. Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol 2000; 31: 117–65PubMedCrossRefGoogle Scholar
  21. 21.
    Adam A, Marzuki A, Rahman HA, et al. The oral and intratracheal toxicities of Roundup and its components to rats. Vet Hum Toxicol 1997; 39: 147–51PubMedGoogle Scholar
  22. 22.
    Baba Y, Takeda M, Yosino K, et al. Acute toxicity of the herbicide ‘Roundup’ in the rat. Jpn J Toxicol 1989; 2: 397–400Google Scholar
  23. 23.
    Tai T, Yamashita M, Wakimori H. Hemodynamic effects of roundup, glyphosate and surfactant in dogs. Jpn J Toxicol 1990; 3: 63–8Google Scholar
  24. 24.
    Martinez TT, Long WC, Hiller R. Comparison of the toxicology of the herbicide roundup by oral and pulmonary routes of exposure. Proc West Pharmacol Soc 1990; 33: 193–7PubMedGoogle Scholar
  25. 25.
    Martinez TT, Brown K. Oral and pulmonary toxicology of the surfactant used in roundup herbicide. Proc West Pharmacol Soc 1991; 34: 43–6PubMedGoogle Scholar
  26. 26.
    Chan PC, Mahler JF. NTP technical report on the toxicity studies of glyphosate (CAS no. 1071-83-6) administered in dosed feed to F344/N rats and B6C3F1 mice. Toxic Rep Ser 1992; 16: 1–D3PubMedGoogle Scholar
  27. 27.
    Brewster DW, Warren J, Hopkins II WE. Metabolism of glyphosate in Sprague-Dawley rats: tissue distribution, identification, and quantitation of glyphosate-derived materials following a single oral dose. Fundam Appl Toxicol 1991; 17: 43–51PubMedCrossRefGoogle Scholar
  28. 28.
    Talbot A, Ku TS, Chen CL, et al. Glyphosate levels in acute Roundup herbicide poisoning. 1994 Toxicology World Congress Abstracts. Ann Emerg Med 1995; 26: 717Google Scholar
  29. 29.
    Tominack RL. Glyphosate: contemporary clinical features. J Toxicol Clin Toxicol 1999; 37: 374–5Google Scholar
  30. 30.
    Hori Y, Fujisawa M, Shimada K, et al. Determination of the herbicide glyphosate and its metabolite in biological specimens by gas chromatography-mass spectrometry: a case of poisoning by Roundup® herbicide. J Anal Toxicol 2003; 27: 162–6PubMedGoogle Scholar
  31. 31.
    Wester RC, Melendres J, Sarason R, et al. Glyphosate skin binding, absorption, residual tissue distribution, and skin decontamination. Fundam Appl Toxicol 1991; 16: 725–32PubMedCrossRefGoogle Scholar
  32. 32.
    Maibach HI. Irritation, sensitization, photoirritation and photosensitization assays with a glyphosate herbicide. Contact Dermatitis 1986; 15: 152–6PubMedCrossRefGoogle Scholar
  33. 33.
    Franz JE, Mao MK, Sikorski JA. Glyphosate: a unique global herbicide. Washington, DC: American Chemical Society, 1997Google Scholar
  34. 34.
    Acquavella JF, Alexander BH, Mandel JS, et al. Glyphosate biomonitoring for farmers and their families: results from the Farm Family Exposure Study. Environ Health Perspect 2004; 112: 321–6PubMedCrossRefGoogle Scholar
  35. 35.
    Temple WA, Smith NA. Glyphosate herbicide poisoning experience in New Zealand. N Z Med J 1992; 105: 173–4PubMedGoogle Scholar
  36. 36.
    Chang C-Y, Peng Y-C, Hung D-Z, et al. Clinical impact of upper gastrointestinal tract injuries in glyphosate-surfactant oral intoxication. Hum Exp Toxicol 1999; 18: 475–8PubMedCrossRefGoogle Scholar
  37. 37.
    Stella J, Ryan M. Glyphosate herbicide formulation: a potentially lethal ingestion. Emerg Med Australas 2004; 16: 235–9PubMedCrossRefGoogle Scholar
  38. 38.
    Delcenserie R, Yzet T, Duchmann JC, et al. Syndrome pseudo-appendiculaire tardif après intoxication au Roundup. Gastroenterol Clin Biol 1997; 21: 435–7PubMedGoogle Scholar
  39. 39.
    Hung D-Z, Deng J-F, Wu T-C. Laryngeal survey in glyphosate intoxication: a pathophysiological investigation. Hum Exp Toxicol 1997; 16: 596–9PubMedCrossRefGoogle Scholar
  40. 40.
    Yang C-C, Lin T-J, Ger J, et al. Possible bronchial asthma necessitating prolonged mechanical ventilation in a patient with Roundup poisoning. 1994 Toxicology World Congress Abstracts. Ann Emerg Med 1995; 26: 722–3Google Scholar
  41. 41.
    Menkes D, Temple WA, Edwards IR. Intentional self-poisoning with glyphosate-containing herbicides. Hum Exp Toxicol 1991; 10: 103–7PubMedCrossRefGoogle Scholar
  42. 42.
    Lin C-M, Lai C-P, Fang T-C, et al. Cardiogenic shock in a patient with glyphosate-surfactant poisoning. J Formos Med Assoc 1999; 98: 698–700PubMedGoogle Scholar
  43. 43.
    Rodriguez A, Echechipia S, O’Laguibel JM, et al. Occupational contact allergy to herbicide glyphosate [abstract]. J Allergy Clin Immunol 1997; 99: S336Google Scholar
  44. 44.
    Amerio P, Motta A, Toto P, et al. Skin toxicity from glyphosate-surfactant formulation. J Toxicol Clin Toxicol 2004; 42: 317–9PubMedCrossRefGoogle Scholar
  45. 45.
    Hindson C, Diffey B. Phototoxicity of glyphosate in a weedkiller. Contact Dermatitis 1984; 10: 51–2PubMedCrossRefGoogle Scholar
  46. 46.
    Hindson TC, Diffey BL. Phototoxicity of glyphosate in a weedkiller: a correction. Contact Dermatitis 1984; 10: 260CrossRefGoogle Scholar
  47. 47.
    Barbosa ER, Leiros da Costa MD, Bacheschi LA, et al. Parkinsonism after glycine-derivate exposure. Mov Disord 2001; 16: 565–8PubMedCrossRefGoogle Scholar
  48. 48.
    Pushnoy LA, Avnon LS, Carel RS. Herbicide (Roundup) pneumonitis. Chest 1998; 114: 1769–71PubMedCrossRefGoogle Scholar
  49. 49.
    Goldstein DA, Johnson G, Farmer DR, et al. Pneumonitis and herbicide exposure. Chest 1999; 116: 1139PubMedCrossRefGoogle Scholar
  50. 50.
    Carel RS, Pushnoy LA. Pneumonitis and herbicide exposure. Chest 1999; 116: 1139–40CrossRefGoogle Scholar
  51. 51.
    Acquavella JF, Weber JA, Cullen MR, et al. Human ocular effects from self-reported exposures to Roundup herbicides. Hum Exp Toxicol 1999; 18: 479–86PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Sally M. Bradberry
    • 1
  • Alex T. Proudfoot
    • 1
  • J. Allister Vale
    • 1
  1. 1.National Poisons Information Service (Birmingham Centre) and West Midlands Poisons UnitCity HospitalBirminghamUK

Personalised recommendations