238
10 Illustrative Case Study
tive, simplified examples for the risk assessment exercises. The data and information
presented do not necessarily reflect the current production process of acibenzolarS-methyl and Bion ® products, and the mass flows across the different process steps
are simplified and do not balance completely. Further, the methods used here are not
meant to be a comprehensive reflection of the much more in-depth risk assessments
conducted and risk management measures taken by companies on manufacturing
processes and for the use of crop protection products. The primary aim of this
case study is to serve as an exercise that makes use of the tools and methods
presented in earlier chapters, and it does not represent a judgment of, or provide
any recommendations regarding, Bion ® products.
Before starting, it will be helpful to first become familiar with plant protection
products in general and to understand the intended use of Bion ® . As a first step,
perform a search for information related to the use of plant protection products in
the European Union via EU government websites (see, e.g., European Commission,
2019b; EFSA, 2019). Then review the material safety data sheets (MSDS) and
labeling information specifically for Bion ® (see Syngenta, 2018). Once these are
in hand, complete this first task:
Task: Summarize the application of and some possible challenges involved in using
plant protection products. Consider the following guiding questions:
(a) What are plant protection products? Why are they used?
(b) Which properties in plant protection products are desired and which are
undesired? Why?
(c) How does Bion ® work, and what advantages does it offer according to the
manufacturer?
10.2 Process Risk Assessment
To better understand Bion ® as a product, it is helpful to take a closer look at
how it is produced. The overall synthesis route for the production of the active
ingredient ASM is shown in Fig. 10.1. In this section, the procedure of process risk
assessment (as introduced in Chap. 7) will be applied specifically to one reaction
step within the synthesis route of ASM: the reaction of 3-chloro-2-isopropylthio
aniline with copper(I) cyanide to give 3-amino-2-isopropylthio benzonitrile, as
shown in Fig. 10.2.
This is a nucleophilic aromatic substitution reaction called the Rosenmund-von
Braun reaction. 1 The reaction mechanism corresponds to a two-stage additionelimination, where copper cyanide forms a bond to the aryl halide through oxidative
addition, and copper chloride then leaves the molecule via reductive elimination.
1 In a Rosenmund-von Braun reaction, an aryl halide reacts to an aryl nitrile in the presence of
copper(I) cyanide in a polar high-boiling solvent such as 3-methylpyridine (Zanon et al., 2003).
10 Illustrative Case Study
tive, simplified examples for the risk assessment exercises. The data and information
presented do not necessarily reflect the current production process of acibenzolarS-methyl and Bion ® products, and the mass flows across the different process steps
are simplified and do not balance completely. Further, the methods used here are not
meant to be a comprehensive reflection of the much more in-depth risk assessments
conducted and risk management measures taken by companies on manufacturing
processes and for the use of crop protection products. The primary aim of this
case study is to serve as an exercise that makes use of the tools and methods
presented in earlier chapters, and it does not represent a judgment of, or provide
any recommendations regarding, Bion ® products.
Before starting, it will be helpful to first become familiar with plant protection
products in general and to understand the intended use of Bion ® . As a first step,
perform a search for information related to the use of plant protection products in
the European Union via EU government websites (see, e.g., European Commission,
2019b; EFSA, 2019). Then review the material safety data sheets (MSDS) and
labeling information specifically for Bion ® (see Syngenta, 2018). Once these are
in hand, complete this first task:
Task: Summarize the application of and some possible challenges involved in using
plant protection products. Consider the following guiding questions:
(a) What are plant protection products? Why are they used?
(b) Which properties in plant protection products are desired and which are
undesired? Why?
(c) How does Bion ® work, and what advantages does it offer according to the
manufacturer?
10.2 Process Risk Assessment
To better understand Bion ® as a product, it is helpful to take a closer look at
how it is produced. The overall synthesis route for the production of the active
ingredient ASM is shown in Fig. 10.1. In this section, the procedure of process risk
assessment (as introduced in Chap. 7) will be applied specifically to one reaction
step within the synthesis route of ASM: the reaction of 3-chloro-2-isopropylthio
aniline with copper(I) cyanide to give 3-amino-2-isopropylthio benzonitrile, as
shown in Fig. 10.2.
This is a nucleophilic aromatic substitution reaction called the Rosenmund-von
Braun reaction. 1 The reaction mechanism corresponds to a two-stage additionelimination, where copper cyanide forms a bond to the aryl halide through oxidative
addition, and copper chloride then leaves the molecule via reductive elimination.
1 In a Rosenmund-von Braun reaction, an aryl halide reacts to an aryl nitrile in the presence of
copper(I) cyanide in a polar high-boiling solvent such as 3-methylpyridine (Zanon et al., 2003).