Azinphos-methyl

Azinphos methyl (Guthion) (also spelled azinophos methyl) is a broad spectrum organophosphate insecticide manufactured by Bayer CropScience, Gowan Co., and Makhteshim Agan. Like other pesticides in this class, it owes its insecticidal properties (and human toxicity) to the fact that it is an acetylcholinesterase inhibitor (the same mechanism is responsible for the toxic effects of the V series nerve agent chemical weapons). It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U. S. Emergency Planning and Community Right to Know Act (42 U. S. C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.

Azinphos methyl is a neurotoxin derived from nerve agents developed during World War II. It is not registered for consumer or residential use. It has been linked to health problems of farmers who apply it, and the U. S. Environmental Protection Agency (EPA) considered a denial of reregistration, citing, “concern to farm workers, pesticide applicators, and aquatic ecosystems. Azinphos methyl has been banned in the European Union since 2006 and in Turkey since 2013. In 2014, it was still used in Australia and partly in New Zealand.

Azinphos methyl can enter the body via inhalation, ingestion and dermal contact. Ingestion of azinphos methyl is responsible for the low dose exposure to a large part of the population, due to their presence as residues in food and drinking water. After ingestion it can be absorbed from the digestive tract. By skin contact, AzM can also enter the body through dermal cells. At high concentrations AzM itself can be toxic because it can function as an acetylcholinesterase (AChE) inhibitor. But its toxicity is mainly due to the bioactivation by a cytochrome P450 (CYP450) mediated desulfuration to its phosphate triester or oxon(gutoxon) (see figure 2). Thus the inhibition of the enzyme AChE may have a lot of different effects.

To prevent the toxic effects, AzM can be biotransformed. Although AzM (in figure 2 named guthion) can be bioactivated by a cytochrome P450 (CYP450) mediated desulfuration to its phosphate triester or oxon (gutoxon), it may also be detoxified by CYP itself (reaction 2 in figure 2).

There are two different main mechanism of treatment for toxification with AzM. One possibility is to treat the patient before exposure to AzM and the other one is to treat the patient after poisoning. Competitive antagonists of AChE can be used for pre treatment. They can reduce mortality, which is caused by exposure to AzM. Organophosphorus AChE inhibitors can bind temporally to the catalytic site of the enzyme. Because of this binding, AzM cannot phosphorylate the enzyme anymore and the enzyme is shorter inhibited. There are a few oximes that are the most efficacious by AzM poisoning, namely oxime K 27 and physostigmine. In general, pretreatment is much more efficient than post treatment.