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Cholinergic Agonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar
For conferring the resistance to mammalians, malathion needs to change sulfur atom with oxygen in vivo. Detoxification occurs by hydrolysis of the carboxyl ester linkage by plasma carboxylesterases, whose activity indicates species resistance to malathion. Mammals and birds show a rapid detoxification reaction than in insects (Costa et al., 2003). Recently, malathion has been used in aerial spraying of relatively popular areas for control of citrus orchard-destructive Mediterranean fruitflies and mosquitoes that harbor and transmit viruses harmful to human beings, such as the West Nile encephalitis virus. Suicide attempts or deliberate poisoning is responsible for acute toxicity from malathion. The lethal dose of malathion in mammals is approximately 1 g/kg and skin–skin exposure leads to systemic absorption of a small fraction (<10%). In the management of pediculosis (lice) infestations, it is used as a topical preparation. Parathion and methyl parathion were widely used as insecticides because of their less volatility and good aqueous stability (Brunton, 2011).
Rationale and technique of malaria control
Published in David A Warrell, Herbert M Gilles, Essential Malariology, 2017
David A Warrell, Herbert M Gilles
All insecticides are, to some degree, harmful to animals and to humans, but there is a major difference between the toxicity of a given compound and the hazard that it presents. Highly toxic compounds are excluded from use in vector control because of the difficulty of reducing human exposure to them. A measure of potential toxicity of a given insecticide to humans or other mammals is the oral or dermal LD50 value, i.e. the estimate of the amount of toxicant per kilogram of body weight required to kill 50 per cent of experimental animals (usually rats) used for testing (see Table 6.4). According to this table, parathion (an agricultural insecticide) is the most toxic and temephos the least toxic organophosphorous compound if taken by mouth. The apparently low toxicity of malathion may be misleading because some formulations may become toxic in tropical conditions, especially if not stored properly. Such an unexpected change in an insecticide with a previous good safety record was seen in 1976 in Pakistan, where about 2500 cases of illness occurred among spraypersons, five of whom died. An investigation showed that the major toxic component was isomalathion, formed in malathion dispersible powder during prolonged storage in tropical conditions. This unfortunate episode, while revealing a new problem, indicated ways for the improvement of insecticide formulations.
Anticholinesterases
Published in Kenneth J. Broadley, Autonomic Pharmacology, 2017
Parathion is more toxic than malathion and, although used extensively in agriculture, it has been replaced for domestic use as an insecticide by less hazardous alternatives. It has been a widespread source of accidental death through mishandling. Absorption of all the organophosphorus compounds readily occurs by all routes – inhalation of aerosols, cutaneous penetration and via the gastrointestinal tract.
Apoptosis is involved in paraoxon-induced histological changes in rat cerebellum
Published in Drug and Chemical Toxicology, 2022
Zohreh Zare, Sam Zarbakhsh, Shamim Mashhadban, Afshin Moradgholi, Moslem Mohammadi
Organophosphate (OP) compounds are cholinesterase inhibitors commonly used as nerve agents on the battlefield and as insecticides in agriculture (Collombet 2011). Parathion is an OP insecticide that requires metabolic activation by the cytochrome P450 (CYP) system to become biologically active. Paraoxon is the active neurotoxic metabolite of parathion (Carr et al. 2002, Rocha et al. 1996). The OP compounds exert their primary toxic effects through binding, phosphorylation, and inhibition of the acetylcholinesterase (AChE), followed by accumulation of acetylcholine (ACh) in the synaptic clefts and development of cholinergic crisis (Chowdhary et al. 2014, Howard et al. 2007). The onset of seizure activity by OP-induced repetitive stimulation of central muscarinic receptors and its maintenance and progression by recruitment of other neurotransmitter systems contribute to neuronal damage and brain histopathology (McDonough and Shih 1997, Mohammadi et al. 2016).
Lipid emulsion for the treatment of acute organophosphate poisoning: an Open-Label randomized trial
Published in Clinical Toxicology, 2022
Ashok Kumar Pannu, Sahil Garg, Ashish Bhalla, Deba Prasad Dhibar, Navneet Sharma
Our results contrast animal data, case reports, and nonrandomized case series, most of which suggest that ILE has beneficial effects in OP poisoning [20–23,34–36]. The explanation for the failure of ILE to affect clinical outcomes substantially in our trial is not clear. Some experts believe that ILE does not sequester the toxin but may behave as a mere transport vehicle akin to extra tissue-binding sites [42]. Furthermore, it may stabilize the OP from degradation [43]. An Iranian rodent study [44] demonstrated no benefit of ILE for diazinon (a highly lipid-soluble OP), likely due to its conversion into a potent and less lipid-soluble compound. Most OPs ingested by our study patients (i.e., chlorpyrifos, phorate, triazophos) were highly lipophilic, albeit more than half of the compounds remained unidentified [36]. Regardless of the explanation, our findings weaken the concept that the ‘lipid sink’ approach is a useful treatment option for reducing morbidity and CFR in OP poisoning. However, it remains possible that poisoning of the OP, different from the one ingested in our study patients, might benefit with ILE, as was observed with malathion and parathion compounds by animal data and case reports [20–22,34–36].
Degradation of phosalone by silver ion catalytic hydrolysis
Published in Toxicology Mechanisms and Methods, 2021
Jalal Hassan, Roya Kamrani, Hadi Tabarraei, Fardad Pirri, Mohammad Rezaian Nojani, A. Wallace Hayes
Pesticides are used to control pests, including weeds. Insects, weeds, and plant diseases are responsible for about 40% of the overall damage in agriculture; therefore, the application of pesticides to ameliorate such damage is currently used to improve crop yield necessary to fed an ever-growing world population. In general, a pesticide deters, incapacitates, kills, or otherwise discourages pests. The most widely used pesticides are herbicides which account for approximately 80% of total pesticide usage. Along with these benefits, pesticides, which are biologically active compounds, may cause toxicity to nontarget species including humans and other species in the environment. The organophosphates (phosphate esters, or OPs) are one of the most commonly used classes of insecticides. It is estimated that more than 2 million tons of OPs are utilizing annually for agricultural purposes globally (Paoletti and Pimentel 2000). Malathion, parathion, chlorpyrifos, diazinon, and phosalone are examples of OP pesticides. OPs are neurotoxic agents that inhibit acetylcholinesterase, a vital enzyme for nervous system transmission (Sharma et al. 2019).