**5.1 Insecticides**

Insecticides Resistance Action Committee (IRAC) has classified insecticides into 32 groups based on their mode/site of action, in addition, there are 5 other types of insecticides with unknown modes of action. Most commonly used insecticides work at different sites in the nervous system of insects. Insecticides target the same sites of action in human nervous system and cause toxicity with adverse health effects. Carbamate (group 1A) and Organophosphate (OP) (group 1B) insecticides inhibit the enzyme Acetyl Choline Esterase (AChE) and cause hyper-excitation. AChE terminates the action of the excitatory neurotransmitter acetylcholine at the nerve synapses. Examples of pesticides inhibiting AChE include dichlorvos, malathion, phorate, carbaryl, carbofuran, etc. Cyclodiene organochlorine insecticides (OC) (group 2A) and phenylpyrazoles (group 2B) block the gamma amino butyric acid (GABA)-activated chloride channel causing hyper-excitation and convulsions. GABA is the major inhibitory neurotransmitter in insects. Examples of insecticides inhibiting GABA include endosulfan and fipronil. Synthetic pyrethroids and natural pyrethrins (group 3A) and DDT (group 3B) keep sodium channels open causing hyper-excitation and, in some cases, nerve blockage. Sodium channels are involved in the propagation of action potentials along nerve axons. Examples include deltamethrin and permethrin. Neonicotinoid insecticides (group 4A) bind to the acetylcholine site on nicotinic acetylcholine receptor (nAChRs) causing a range of symptoms from hyper-excitation to lethargy and paralysis. Examples include acetamiprid, clothianidin, imidacloprid, thiacloprid and thiamethoxam. Other groups of insecticides that work on nervous system includes those which allosterically activate nAChRs (e.g. spinetoram, spinosad) or glutamate-gated chloride channels (GluCls) (e.g. abamectin, emamectin benzoate), or allosterically inhibit the GABA-activated chloride channel and cause paralysis (e.g. broflanilide and fluxametamide). Glutamate is an important inhibitory neurotransmitter in insects. Other insecticides will block the nAChR ion channel or sodium channels, e.g. indoxacarb, cause nervous system shutdown and paralysis.

#### **5.2 Fungicides**

Fungicides inhibit fungal growth by interfering with critical cellular processes. Fungicide resistance action committee (FRAC) classify fungicides and bactericides into 50 groups based on the site of action. Within each group, there are target sites, which are the specific enzymes to which the fungicides bind. The different known target sites include nucleic acids metabolism, cytoskeleton and motor protein, respiration, amino acids and protein synthesis, signal transduction, lipid synthesis or transport/membrane integrity or function, sterol biosynthesis in membranes, cell wall biosynthesis, melanin synthesis in cell wall and host plant defense induction. Some fungicides and herbicides are considered endocrine disrupting pesticides.

#### **5.3 Herbicides**

Herbicides are pesticides that inhibit or interrupt normal plant growth and development. Herbicides are widely used in agriculture, landscape industry, and non-crop areas for weed management. Herbicides resistance action committee (HRAC) has classified herbicides into 27 groups. These include: growth regulators (synthetic auxins; auxin transport inhibitors), seedling growth inhibitors, photosynthetic inhibitors, amino acid synthesis inhibitors, lipid synthesis inhibitors, cell membrane disrupters, pigment inhibitors.

Growth regulator herbicides consist of the synthetic auxin and auxin transport inhibitory compounds and the most commonly used synthetic auxins include 2,4-*Dichlorophenoxyacetic acid* (2,4-D)*,* fluroxypyr, dicamba, quinclorac, dichlorprop, MCPA (2-methyl-4-chlorophenoxyacetic acid), mecoprop and picloram. These are commonly used systemic herbicides which mimic the plant growth hormone auxin (indole acetic acid) [4]. Some of these synthetic auxin herbicides disrupt human hormonal system. Atrazine is also a commonly used photosynthetic inhibitor herbicide. Glyphosate (Roundup) is an amino acid derivative and inhibits synthase of EPSPS enzyme, which is involved in the synthesis of the aromatic amino acids (tyrosine, tryptophan, and phenylalanine). Paraquat (gramoxone) is an electron diverter, and as a respiratory inhibitor can be a significant risk to humans if inhaled or ingested.
