**1. Introduction**

After World War II, the world was in the need to overcome food scarcity. Therefore, several pest and weed management techniques were adopted by farmers all over the world using various synthetic herbicides. The invention of glyphosate (GLY; N-(phosphonomethyl) glycine) was a big breakthrough in that era. GLY with CAS No. 1071-83-6 is a broad-spectrum, postemergent, nonselective, and synthetic universal herbicide, whose commercial formulations are referred to as glyphosate-based herbicides (GBHs) [1, 2]. Glyphosate was first synthesized in 1950 by Swiss chemist Henry Martin, who worked for the Swiss company Cilag. The work was never published. Its herbicidal activity was not discovered until GBHs were resynthesized and tested in 1970, being used for this purpose since 1974. It was the Monsanto Corporation in 1974 that introduced and made commercially available the herbicidal formulation Roundup containing GLY as active substance. Farmers quickly adopted glyphosate for agricultural weed control, gaining the potential to kill weeds without killing their crops. Indeed, glyphosate proved able to kill weeds without killing their crops, especially annual broadleaf weeds and grasses known to compete with commercial

crops grown around the globe by interfering with the synthesis of the aromatic amino acids phenylalanine, tyrosine, and tryptophan [3].

Since then, its use in agricultural and nonagricultural settings has steadily increased from a total of 0.6 Mg applied in 1974 to a total of 125.5 Mg applied in 2014, and it is currently the most widely used herbicide in the United States and throughout the world [4, 5]. Monsanto's last commercially relevant US patent expired in 2000. Nowadays, GLY formulations that are used as a broad-spectrum systemic herbicide have been widely applied in agronomic crops and orchards. Furthermore, GLY formulations are currently approved by regulatory bodies and marketed worldwide by many agrochemical companies, such as Bayer, Dow AgroSciences, and Monsanto, in different solution strengths and with various adjuvants.

GLY approval is renewed in the European Union (EU) on 16 December 2017, while its approval expires on 15 December 2022. Therefore, GLY can be used as an active substance in plant protection products (PPPs), until 15 December 2022. GLY has been thoroughly assessed, under an intense debate due to a concern about its effects on the environment and human health, by the Member States, the European Chemicals Agency (ECHA), and the European Food Safety Authority (EFSA) in recent years [6, 7]. An important prerequisite for GLY upcoming renewal as an ingredient in PPPs is that GLY should not adversely affect the environment and human and animal health as delineated by European regulation [8].
