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Biomonitoring in Occupational Exposure to Glyphosate: Comparison
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Please note this is a comparison between Version 2 by Camila Xu and Version 1 by Lenard Farczadi.

Glyphosate, also known under its IUPAC name N-(phosphonomethyl) glycine, while discovered by a Swiss chemist, Dr. Henri Martin, was initially developed as a chemical chelating agent, a chemical intermediate for the synthesis of other molecules, and as a possible bioactive compound.

  • glyphosate
  • exposure
  • biomonitoring
  • bioanalytical methods

1. Introduction and Background—Glyphosate Use and Exposure

Glyphosate, also known under its IUPAC name N-(phosphonomethyl) glycine, while discovered by a Swiss chemist, Dr. Henri Martin [1], was initially developed as a chemical chelating agent, a chemical intermediate for the synthesis of other molecules, and as a possible bioactive compound [2]. Independently, sometime later, due to the potential of chelating metals, a number of derivatives of aminomethylphosphonic acid (Figure 1) including glyphosate (Figure 1) were studied as potential water-softening agents [1]. During the research, however, the herbicidal activity of some of these compounds was discovered, and after some study, glyphosate was discovered to be a promising candidate for such use [1]. Not long after this discovery, the first commercial formulation of glyphosate to be used as a broad-spectrum weedkiller was created [1].
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Figure 1.
Chemical structure of glyphosate (
left
) and aminomethylphosphonic acid (
right
).
Glyphosate base plant protection products are effective herbicides by inhibiting an important plant enzyme, 5-enolpyruvylshikimate-3-phosphate synthase, which is present in plants and fungi, but not in animals and humans [3]. This enzyme is part of the biological mechanism during which plants synthesize aromatic amino acids. These amino acids are essential in many ways for the survival and growth of plants; thus, glyphosate inhibits the plant from functioning normally and slowly leads to the deterioration of the plant, both overground and underground. Loss of herbicidal activity occurs through the hydrolysis of glyphosate into its main metabolite aminomethylphosphonic acid (AMPA) [3].
To improve the efficacy of glyphosate, modified crops have been developed, which are resistant to glyphosate by genetically engineering plants to express genes from a type of bacteria, after discovering that it contained a form of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase, which is not inhibited by glyphosate [4]. This made the use of glyphosate the first choice for crop farming as it facilitated the destruction of unwanted weeds without affecting crops.
Glyphosate is a polar, readily water-soluble compound; it tends to partition in water versus air and easily absorbs into the soil particles. During application, small quantities of aerial drifts, splash, or drip can cause harm to non-target surrounding plants. Glyphosate is highly chemically stable in water in a wide pH-range and is not photosensitive to degradation from sunlight. The main path of the decomposition of glyphosate in water and soil particles is through microbial degradation and is dependent on the type and number of microorganisms [3].
Due to its wide use in recent years, concerns have grown with regard to its toxicity and the health risks involved with exposure to glyphosate and glyphosate-based herbicides [5]. While some regulatory agencies consider that it does not pose a risk to public health and that it is unlikely to be carcinogenic to humans [6[6][7],7], others have concluded that it is a “probably carcinogenic” substance to humans [8]. Most regulatory authorities, however, have concluded that it is necessary to limit the human intake of glyphosate. Although it is a controversial topic and it is still debated whether it has a role as a tumor cell initiator or promoter, and studies are still ongoing, there are results that have shown the cytotoxicity, involvement in genetic damage, and even some tumor promoting activity of glyphosate [9,10][9][10].
In 2017, the license for glyphosate use in the European Union was renewed for five more years until December 2022, after the previous 15-year license had expired, causing a controversial and highly divisive debate [11]. As glyphosate residues have been detected in food, groundwater, and even drinking water [12[12][13],13], most regulatory agencies around the world, even those that have classified it as posing no risk to public health, have imposed limits on the exposure and intake for humans, currently at 1.75 mg/kg bw/day in the USA and 0.5 mg/kg bw/day in the EU (increased in 2015 from 0.3 mg/kg bw/day) [13,14,15][13][14][15]. Some independent scientists, however, consider these limits to be too high, suggesting an acceptable daily intake of 0.1 mg/kg bw/day or less [16].
Biomonitoring in glyphosate exposure is not only a challenge, but is should also be a must for both the occupational and non-occupational exposed population, considering the high amount of usage worldwide. For example, in the European Union, the total glyphosate sales in 2017 reached 44,250 tons, accounting for a proportion of 34% of all herbicides [17]. It is estimated that around 11–13% of agricultural workers are exposed to glyphosate [18], which makes the need for glyphosate biomonitoring of even greater need.
In a series of 13 acute glyphosate poisonings, Zouaoui et al. [19] described the associated symptoms such as respiratory alteration, oral and pharynges ulceration, hepatic and renal toxicity, cardiac arrest, laboratory parameters disturbed, and many other affected organs. The authors indicated a mean value of 61 mg/L glyphosate in blood in mild–moderate intoxication, a mean concentration about fourteen times greater in severe intoxication, and sixty-eight times higher in mortal cases.
During a study performed on farmers of different crops in Thailand, Wongta et al. found that the occupational exposure of the farm worker groups led to significant, quantifiable levels of glyphosate in the urine of a large percentage of them compared to a control group that showed no detectable urinary glyphosate [20]. Urine concentrations were between an average of 2.01 ng/mL and 3.11 ng/mL for the different types of farmer groups and was thought to be worsened by the lack of protective equipment for the farm workers. Similar previous studies performed by researchers in this group have also shown that the occupational exposure of farm workers from other regions of Thailand have similar quantifiable glyphosate levels in urine [20].
A study by Melissa Perry et al. on historical urine samples collected decades prior from American farmers exposed to glyphosate also showed that compared to non-users who had no detectable traces of glyphosate in their urine, the farmers actively using glyphosate on their crops, for the most part, had quantifiable levels of urinary glyphosate with an average of 4.04 μg/kg urine, and as high as 12.0 μg/kg urine [21].

2. Difficulties in Laboratory Assessment of Glyphosate—Ongoing Research

Rapid and reliable analytical techniques are essential in clinical chemistry because they enable timely and precise diagnosis and appropriate treatment [22], and this is essential in the field of occupational medicine for a proper biomonitoring strategy in occupational exposure to glyphosate. Occupational exposure to glyphosate can have the direct pathway through inhalation or topic absorption during the application of herbicide products based on glyphosate, but there can also be a secondary source of exposure through drinking water and food contaminated with glyphosate (Figure 2).
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Figure 2. Sources of exposure to glyphosate [23,24].
Sources of exposure to glyphosate [23][24].
There are many types of analytical techniques that can be used for the detection and quantification of glyphosate and similar compounds. For environmental and food analysis (water, soil, plants), the most widely used techniques involve liquid chromatography, for example, high pressure liquid chromatography (HPLC) with either ultraviolet detection (UV) or fluorescence detectors (FLD) and liquid chromatography coupled with mass spectrometric detection (LC-MS or LC-ICP-MS), but methods also exist that use ion chromatography (IC) [22,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43][22][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. For bioanalytical and biomonitoring purposes, methods for glyphosate determination in biological matrices (urine, blood, plasma, serum) described in the literature have mostly used liquid chromatography techniques coupled with different types of detection (ultraviolet, fluorescence, but most often mass spectrometry) [19,21,36,37,38,39,44,45][19][21][36][37][38][39][44][45]. Other techniques such as gas chromatography (GC), which is also frequently coupled with mass spectrometry (GC-MS), ion chromatography coupled with mass spectrometric detection [46], and the enzyme-linked immunosorbent assay (ELISA) have also been used for glyphosate determination [21,25][21][25]. More recent developments include the tentative use of electrochemical sensors for the detection of glyphosate from different types of matrices [36]. Choosing the right technique and developing a suitable method, however, might not always be straight-forward, and it is important to choose the correct technique depending on the exact application, as each technique has its own advantages and drawbacks. Likewise, regardless of the technique, the method must be optimized for the application to ensure the proper sensitivity, selectivity, and robustness of the measurements and thus obtain accurate and reliable results. One must also always take into account the availability of the equipment and performance of the equipment that is available as well as the cost of the analytical determination and funding available. Some techniques might offer better sensitivity, selectivity, and/or robustness, which, depending on the application, might not even be necessary, but require better, more expensive equipment, longer sample preparation times, and can lead to increased costs.

References

  1. Dill, G.M.; Douglas Sammons, R.; Feng, P.C.; Kohn, F.; Kretzmer, K.; Mehrsheikh, A.; Bleeke, M.; Honegger, J.L.; Farmer, D.; Wright, D.; et al. Glyphosate: Discovery, Development, Applications, and Properties. In Glyphosate Resistance in Crops and Weeds: History, Development, and Management; Nandula, V.K., Ed.; Wiley Online Library: Hoboken, NJ, USA, 2010; pp. 2–34.
  2. Fon, T.A.D.; Uhing, E.H. Aminomethylenephosphonic Acids, Salts Thereof, and Process for Their Production. U.S. Patent 3,160,632, 8 December 1964.
  3. Schuette, J. Environmental Fate of Glyphosate; Environmental Monitoring & Pest Management Department of Pesticide Regulation Sacramento: Sacramento, CA, USA, 1998.
  4. Pollegioni, L.; Schonbrunn, E.; Siehl, D. Molecular basis of glyphosate resistance—Different approaches through protein engineering. FEBS J. 2011, 278, 2753–2766.
  5. Nagy, K.; Tessema, R.A.; Szász, I.; Smeirat, T.; Al Rajo, A.; Ádám, B. Micronucleus Formation Induced by Glyphosate and Glyphosate-Based Herbicides in Human Peripheral White Blood Cells. Front. Public Health 2021, 9, 639143.
  6. United States Environmental Protection Agency—Ingredients Used in Pesticide Products: Glyphosate. Available online: https://www.epa.gov/ingredients-used-pesticide-products/glyphosate (accessed on 10 October 2022).
  7. European Food Safety Authority—Glyphosate: EFSA Updates Toxicological Profile. Available online: https://www.efsa.europa.eu/en/press/news/151112 (accessed on 10 October 2022).
  8. International Agency for Research on Cancer—IARC Monographs Volume 112: Evaluation of Five Organophosphate Insecticides and Herbicides. Available online: https://www.iarc.who.int/wp-content/uploads/2018/07/MonographVolume112-1.pdf (accessed on 10 October 2022).
  9. Suárez-Larios, K.; Salazar-Martínez, A.-M.; Montero-Montoya, R. Screening of Pesticides with the Potential of Inducing DSB and Successive Recombinational Repair. J. Toxicol. 2017, 2017, 1–9.
  10. George, J.; Prasad, S.; Mahmood, Z.; Shukla, Y. Studies on glyphosate-induced carcinogenicity in mouse skin: A proteomic approach. J. Proteom. 2010, 73, 951.
  11. Glyphosate Gets Five-Year Respite as License Renewed. Available online: https://www.foodnavigator.com/Article/2017/11/28/Glyphosate-gets-five-year-respite-as-license-renewed (accessed on 10 October 2022).
  12. Rendón-von Osten, J.; Dzul-Caamal, R. Glyphosate Residues in Groundwater, Drinking Water and Urine of Subsistence Farmers from Intensive Agriculture Localities: A Survey in Hopelchén, Campeche, Mexico. Int. J. Environ. Res. Public Health 2017, 14, 595.
  13. Myers, J.P.; Antoniou, M.N.; Blumberg, B.; Carroll, L.; Colborn, T.; Everett, L.G.; Hansen, M.; Landrigan, P.J.; Lanphear, B.P.; Mesnage, R.; et al. Concerns over use of glyphosate-based herbicides and risks associated with exposures: A consensus statement. Environ. Health 2016, 15, 19.
  14. Székács, A.; Darvas, B. Re-registration Challenges of Glyphosate in the European Union. Front. Environ. Sci. 2018, 6, 78.
  15. Center for Food Safety—Major Flaws in European Glyphosate Assessment. Available online: https://www.centerforfoodsafety.org/press-releases/4121/major-flaws-in-european-glyphosate-assessment (accessed on 10 October 2022).
  16. Buekers, J.; Remy, S.; Bessems, J.; Govarts, E.; Rambaud, L.; Riou, M.; Tratnik, J.S.; Stajnko, A.; Katsonouri, A.; Makris, K.C.; et al. Glyphosate and AMPA in Human Urine of HBM4EU Aligned Studies: Part A Children. Toxics 2022, 10, 470.
  17. Antier, C.; Kudsk, P.; Reboud, X.; Ulber, L.; Baret, P.; Messéan, A. Glyphosate Use in the European Agricultural Sector and a Framework for Its Further Monitoring. Sustainability 2020, 12, 5682.
  18. Rydz, E.; Larsen, K.; Peters, C.E. Estimating Exposure to Three Commonly Used, Potentially Carcinogenic Pesticides (Chlorolathonil, 2,4-D, and Glyphosate) Among Agricultural Workers in Canada. Ann. Work. Expo. Health 2021, 65, 377.
  19. Zouaoui, K.; Dulaurent, S.; Gaulier, J.; Moesch, C.; Lachâtre, G. Determination of glyphosate and AMPA in blood and urine from humans: About 13 cases of acute intoxication. Forensic Sci. Int. 2013, 226, e20.
  20. Wongta, A.; Sawarng, N.; Tongchai, P.; Sutan, K.; Kerdnoi, T.; Prapamontol, T.; Hongsibsong, S. The Pesticide Exposure of People Living in Agricultural Community, Northern Thailand. J. Toxicol. 2018, 2018, 1–7.
  21. Perry, M.J.; Mandrioli, D.; Belpoggi, F.; Manservisi, F.; Panzacchi, S.; Irwin, C. Historical evidence of glyphosate exposure from a US agricultural cohort. Environ. Health 2019, 18, 42.
  22. Saito, T.; Aoki, H.; Namera, A.; Oikawa, H.; Miyazaki, S.; Nakamoto, A.; Inokuchi, S. Mix-mode TiO-C18 Monolith Spin Column Extraction and GC-MS for the Simultaneous Assay of Organophosphorus Compounds and Glufosinate, and Glyphosate in Human Serum and Urine. Anal. Sci. 2011, 27, 999.
  23. United Nations—Food and Agriculture Organization. Guidance on Good Labelling Practices for Pesticides. Available online: https://www.fao.org/3/i4854e/i4854e.pdf (accessed on 3 February 2023).
  24. European Medicines Agency. QRD Guidance on the Use of Approved Pictograms on the Packaging of Veterinary Medicinal Products Authorised via the Centralised, Mutual Recognition and Decentralised Procedures. Available online: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/quality-review-documents-qrd-guidance-use-approved-pictograms-packaging-veterinary-medicinal_en.pdf (accessed on 3 February 2023).
  25. Koskinen, W.C.; Marek, L.J.; Hall, K.E. Analysis of glyphosate andaminomethylphosphonic acid in water, plantmaterials and soil. Pest Manag. Sci. 2016, 72, 423.
  26. Carretta, L.; Cardinali, A.; Marotta, E.; Zanin, G.; Masin, R. A new rapid procedure for simultaneous determination of glyphosate and AMPA in water at sub μg/L level. J. Chromatogr. A 2019, 1600, 65.
  27. Gunarathna, S.; Gunawardana, B.; Jayaweera, M.; Manatunge, J.; Zoysa, K. Glyphosate and AMPA of agricultural soil, surface water, groundwater and sediments in areas prevalent with chronic kidney disease of unknown etiology, Sri Lanka. J. Environ. Sci. Health Part B 2018, 53, 729.
  28. Liao, Y.; Berthion, J.-M.; Colet, I.; Merlo, M.; Nougadère, A.; Hu, R. Validation and application of analytical method for glyphosate and glufosinate in foods by liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 2018, 1549, 31.
  29. Poiger, T.; Buerge, I.J.; Bächli, A.; Müller, M.D.; Balmer, M.E. Occurrence of the herbicide glyphosate and its metabolite AMPA in surface waters in Switzerland determined with on-line solid phase extraction LC-MS/MS. Environ. Sci. Pollut. Res. 2017, 24, 1588.
  30. Ehling, S.; Reddy, T.M. Analysis of Glyphosate and Aminomethylphosphonic Acid in Nutritional Ingredients and Milk by Derivatization with Fluorenylmethyloxycarbonyl Chloride and Liquid Chromatography–Mass Spectrometry. J. Agric. Food Chem. 2015, 63, 10562–10568.
  31. Islas, G.; Rodriguez, J.A.; Mendoza-Huizar, L.H.; Pérez, F.; Carrillo, E.G. Determination of Glyphosate and Aminomethylphosphonic Acid in Soils by Hplc with Pre-Column Derivatization Using 1,2-Naphthoquinone-4-Sulfonate. J. Liq. Chromatogr. Relat. Technol. 2014, 37, 1298.
  32. Farczádi, L.; Moldovan, H.; Duca, R.C.; Imre, S. A Quick, Simple, Sensitive and Selective LC-MS/MS Method Used for the Screening of Ethephon, Glyphosate and Aminomethylphosphonic Acid from Water and Food Samples. ABMJ 2022, 5, 41.
  33. Berni, I.; Menouni, A.; El Ghazi, I.; Godderis, L.; Duca, R.-C.; El Jaafari, S. Health and ecological risk assessment based on pesticide monitoring in Saïss plain (Morocco) groundwater. Environ. Pollut. 2021, 276, 116638.
  34. Kawai, S.; Uno, B.; Tomita, M. Determination of glyphosate and its major metabolite aminomethylphosphonic acid by high-performance liquid chromatography after derivatization with p-toluenesulphonyl chloride. J. Chromatogr. A 1991, 540, 411.
  35. Fontanella, M.C.; Lamastra, L.; Beone, G.M. Determination of Glyphosate in White and Brown Rice with HPLC-ICP-MS/MS. Molecules 2022, 27, 8049.
  36. Zhang, H.; Liu, X.; Huo, Z.; Sun, H.; Zhang, F.; Zhu, B. An ion chromatography tandem mass spectrometry (IC-MS/MS) method for glyphosate and amino methyl phosphoric acid in serum of occupational workers. Microchem. J. 2021, 170, 106614.
  37. Qiu, H.-M.; Geng, J.-J.; Han, C.; Ren, H.-Q. Determination of Phosphite, Phosphate, Glyphosate and Aminomethylphosphonic Acid by Two-Dimensional Ion Chromatography System Coupled with Capillary Ion Chromatography. Chin. J. Anal. Chem. 2013, 41, 1910–1914.
  38. Zambrano-Intriago, L.A.; Amorim, C.G.; Rodríguez-Díaz, J.M.; Araújo, A.N.; Montenegro, M.C. Challenges in the design of electrochemical sensor for glyphosate-based on new materials and biological recognition. Sci. Tota. Environ. 2021, 793, 148496.
  39. Fama, F.; Feltracco, M.; Moro, G.; Barbaro, E.; Bassanello, M.; Gambaro, A.; Zanardi, C. Pesticides monitoring in biological fluids: Mapping the gaps in analytical strategies. Talanta 2023, 253, 123969.
  40. López-Ruiz, R.; Romero-González, R.; Frenich, A.G. Simultaneous determination of polar pesticides in human blood serum by liquid chromatography coupled to triple quadrupole mass spectrometer. J. Pharm. Biomed. Anal. 2020, 190, 113492.
  41. Rocío-Bautista, P.; Moreno-González, D.; Martínez-Piernas, A.B.; García-Reyes, J.F.; Molina-Díaz, A. Novel liquid chromatography/mass spectrometry-based approaches for the determination of glyphosate and related compounds: A review. Trends Environ. Anal. Chem. 2022, 36, e00186.
  42. Melo, K.G.; De Nucci, G.; Trape, A.Z.; Jacobucci, S.R.E.; Garlipp, C.R.; Rosa, P.C.P. Brief review analytical methods for the determination of glyphosate. MOJ Toxicol. 2018, 4, 39.
  43. Verdini, E.; Pecorelli, I. The Current Status of Analytical Methods Applied to the Determination of Polar Pesticides in Food of Animal Origin: A Brief Review. Foods 2022, 11, 1527.
  44. Connolly, A.; Jones, K.; Galea, K.S.; Basinas, I.; Kenny, L.; McGowan, P.; Coggins, M. Exposure assessment using human biomonitoring for glyphosate and fluroxypyr users in amenity horticulture. Int. J. Hyg. Environ. Health 2017, 220, 1064.
  45. Guo, H.; Wang, H.; Zheng, J.; Liu, W.; Zhong, J.; Zhao, Q. Sensitive and rapid determination of glyphosate, glufosinate, bialaphos and metabolites by UPLC–MS/MS using a modified Quick Polar Pesticides Extraction method. Forensic Sci. Int. 2018, 283, 111.
  46. Connolly, A.; Koslitz, S.; Bury, D.; Brüning, T.; Conrad, A.; Kolossa-Gehring, M.; Coggins, M.A.; Koch, H.M. Sensitive and selective quantification of glyphosate and aminomethylphosphonic acid (AMPA) in urine of the general population by gas chromatography-tandem mass spectrometry. J. Chromatogr. B 2020, 1158, 122348.
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