Environmental Challenges

Exposure risk and environmental impacts of glyphosate: Highlights on the toxicity of herbicide co-formulants

Highlights •Global use of glyphosate dates back to the 1970s and it is also linked to the introduction of genetically engineered crops.•The current review details the environmental contamination, exposure, health and ecological impacts of glyphosate and glyphosate-based herbicides.•Glyphosate based herbicides require a detailed risk assessment of adjuvants used for technical formulations as well as the transformation products of glyphosate.•Carcinogenic potential of Glyphosate-based herbicides has been extensively debated issue within many international agencies with contrasting opinions. Abstract Glyphosate is an extensively used herbicide globally. Its use dates back to the 1970s with increasing numbers over the years. It is an effective weed killer but since it parallelly destroys non-target crops, its use during the initial days was restricted. To overcome this, genetically engineered [GE] varieties of many crops entered the market. This led to a significant increase in the usage of glyphosate. Over years of extensive usage, many issues related to toxicity, carcinogenicity and GE varieties cropped up. Many researchers studied the toxicological characteristics, health impacts, environmental exposures and ecological impacts of glyphosate and Glyphosate-based herbicides. Many international agencies assessed its carcinogenic potential and grouped and regrouped it based on the conclusions of various studies. As an outcome of many studies, an important aspect of toxicity of adjuvants used for technical formulations of glyphosate surfaced and gave a better understanding of its overall toxicity. This review summarizes glyphosate history, global use and hazards related to glyphosate and its technical formulations. It also briefs important studies on Environmental and human health exposures and their impact. Environmental contamination due to glyphosate is studied in detail for water and soil matrices besides its presence in food commodities. The impact of glyphosate on the ecosystem, human and animal health has also been detailed. Studies highlighting and inferring the carcinogenic potential of glyphosate are also summed up finally linking the use of glyphosate with the sustainable development goals [SDGs]. The overall conclusions of the review give an insight into the gaps in the current studies particularly mentioning the important role of adjuvants used in technical formulations of pesticides which may go unnoticed in risk assessment studies. Considering the extensive global usage of glyphosate, it is of utmost importance to design toxicological studies and include glyphosate and related adjuvants in the routine monitoring programs of countries. This will help understand the risks and the need to restrict or ban the use of glyphosate. Some important inclusions of disclosing toxicity of active as well as other ingredients/co-formulants on labels should be a mandatory part of pesticide registration.

Glyphosate Glyphosate-based herbicide(GBH) Sustainable development goals(SDGs) Polyoxyethylene amine(POEA) Aminomethylphosphonic acid(AMPA)

1. Glyphosate history and global use In this era of weed management, no other herbicide has influenced the industry and been more prominent than glyphosate (Duke and Powles, 2008). Its historical impact and subsequent genetically modified crops have dramatically changed the scenario of modern farming (Duke and Powles, 2009). Structurally it is a phosphonomethyl derivative of glycine [amino acid], which was discovered in the year 1950 by a swiss researcher, Henri Martin, working in the pharmaceutical company Cilag (Franz et al., 1997). After ten years, the accession of the company was passed on to the laboratory research chemicals distributor, Aldrich Chemical Co., (Székács and Darvas, 2012). Dr. John Franz, a chemist from Monsanto recognized the herbicidal potential of glyphosate in the year 1970 and composed an end-use product named "Roundup". It was first sold by Monsanto in 1974 (Duke and Powles, 2008). This company later on extended the study of Glyphosate concerning their herbicidal activity, and so its potential against ceaseless weeds was perceived (Dill et al., 2010). From its commencement in the 1974, glyphosate acquired a superior position in the pesticide merchandise. Because of glyphosate's mode of action, quick translocation, and the inability of plants to detoxify the herbicide, it became highly effective and the first preference of many agricultural producers (Shaner, 2006). The supposed mode of action of glyphosate in plants is the destruction of the shikimate pathway by inhibition of 5-endopyruvyl-shikimate-3-phosphate synthase (EPSPS) enzyme. This affects the production of vital aromatic amino acids (phenyl amine, tyrosine and tryptophan) (Matozzo et al., 2020). The entire process results in the hampering of protein synthesis and growth and ultimately leads to cellular disarray and death (Salisbury and Ross, 1994). Despite the edge, the amount of glyphosate sold was limited because it could only be sprayed where farmers wanted to destroy whole vegetation [for example, between the rows in industrial yards, orchards and viticulture etc.]. In 1996, herbicide-tolerant [HT], genetically engineered [GE], and “Roundup Ready” [RR], varieties of cotton, soybean and maize, were given consent for sowing in the United States. This technological advancement made it feasible to use glyphosate as a post-emergence herbicide and lead to a significant increase in the time span for which glyphosate-based herbicides could be used (Benbrook, 2016). In 2000, a great change came about when Monsanto's patent on glyphosate ended and the number of firms manufacturing glyphosate extended from one to thirty (Perry et al., 2019). Manufacturing and utilization of glyphosate have risen significantly due to the termination of patent protection and launching of genetically modified glyphosate-tolerant[GT] crop varieties in 1996 (Székács and Darvas, 2012). In 2007, the USA(United States of America) used more than 80,000 tonnes of glyphosate (EPA, 1997; EPA, 2011). This was comparable to that in Asia, which shared for around 30% of world's glyphosate demand in 2012 (Transparency Market Research, 2014). In India, 308 tonnes of glyphosate was produced in 2003–2004, which raised to 2100 tonnes in around 2007–2008 (Ministry of Chemicals and Fertilizers, 2008). Glyphosate got certified in around 130 countries until 2010 and was proclaimed to be the most profoundly used herbicide in the world (Dill et al., 2010). Annual global production of glyphosate is in increasing trend as can be seen in Table 1. Global agricultural and non-agricultural use of glyphosate is detailed in Table 2 (Benbrook, 2016). Table 1. Annual global production volume of glyphosate [2008–2012] (Dill et al., 2010; CCM International, 2011; Hilton, 2012; Transparency Market Research, 2014).200820112012Glyphosate Production volume (in tonnes)600 000650 000720 000 Table 2. Worldwide agricultural and non-agricultural utilization of glyphosate [1995 to 2014] (Adapted from Benbrook, 2016).Yearly Data (in tonnes)199520002005201020122014Glyphosate use67,078193,485402,350652,486718,600825,804Agricultural51,078155,367339,790578,124648,638746,580Non-Agricultural16,00038,11862,56074,36269,96279,224 In addition to its prowess as an effective farming tool, glyphosate has long been considered the safest herbicide in the market as well. In the initial years, Roundup was contemplated to be less toxic to humans, as there had been very little evidence of carcinogenicity or Genotoxicity in mammals (DeRoos et al., 2005). The use of glyphosate and its derivatives as herbicides since its introduction in USA 1974 has increased vastly with the assumption that it has negligible side effects to mammals. However, increased use and excessive dosage have increased concerns regarding its effects on human health and the environment. Increasingly, significant evidence shows that glyphosate herbicides may indeed affect health, stimulating the need for more surveillance (Benachour and Seralini, 2009). A report of World Health Organization (WHO) in 2015 reclassified glyphosate as probably carcinogenic. Thus, it is important to study the potential hazards of glyphosate, acknowledge the pertinence of public concern, and thoughtfully stabilize the concern against agricultural advantages. Previous studies and research were assessed in mammals by health authorities such as the U.S. Environmental Protection Agency [EPA] and they found that there is no indication that glyphosate is toxic to the nervous, immune and reproductive system (