Abstract
Organophosphorus compounds (OPs) are a large and diverse class of chemicals that have been synthesized, since the XIX century for several purposes like chemical weapons, flame-retardants, ectoparasiticides and investigational new drugs, but mainly as agrochemicals in agriculture and indoor. Although the amount of OP pesticides being used is declining, especially in developed countries, OPs continue being one of the most important classes of insecticides and chemical warfare agents today due to its toxic effects on the enzyme acetylcholinesterase (AChE). Existing research on the toxicological effects of OPs is extensive, however, there is a lack of knowledge on the long-term effects of low levels of OPs and their exactly pathways of toxicity. Recent data prove that other molecular targets than AChE could be targeted by OPs, triggering these effects. Here these data are reviewed and it is highlighted that the current uses of OPs are producing several neurotoxic effects. It is also shown that, to protect people from possible uses and misuses of OPs, more regulations on OPs are needed. Moreover, more mechanistic studies are needed to completely understand their toxicological interactions and mechanisms of action and to identify the whole group of enzymes that interact with them.
Highlights
Organophosphorus compounds (OPs) are a large and diverse class of chemicals
The selective toxicity of OP pesticides is based on specific differences in cholinesterase (ChE) targets, more rapid detoxification in mammals than in insects and in the use of pro-insecticides which are activated in insects
Despite the number of compounds acting in other targets than ChEs have increased in the last three decades, OPs and methyl carbamates remain at the top of the list among commercial insecticides[10] and their importance will probably continue for decades, since they are effective and inexpensive.[11]
Summary
Organophosphorus compounds (OPs) are a large and diverse class of chemicals. The first OP, tetraethyl phosphate, was synthesized by Philippe de Clermont, in France in 1854, and OP esters were discovered as toxicants for people in 1932, when Lange and Kruger described the synthesis of dimethyl and diethyl phosphofluoridate and reported that the inhalation of its vapors produced dimness of vision and a choking sensation. When we repeated their approach in December 2015, more 5,500 hits were found since the year 2010 The reasons for these efforts in research activities are the continuous high worldwide use of these compounds as pesticides, especially in developing countries, the uses of OPs as chemical weapons in the last years in Syria and some important questions on their mechanisms of toxicity that need to be clarified, especially in relation to their long term neurotoxicity effects and the existence of non-cholinergic targets in mammals.
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