Poisons malathion

The insecticide malathion was the hero in the 1976 tragedy in Pakistan. Poisoning started after measures were taken to fight malaria. At least 2800 of the 7500 workers in this area were poisoned [37]. When studied, the more highly toxic iso-malathion was found together with malathion in their bodies. It is known that iso-malathion transforms into the more highly toxic malaoxon, both in storage and directly in the environment. 

Baker E.L., Warren M., Zack M. et al. Epidemic Malathion Poisoning in Pakistan Malaria Workers // Lancet. 1978. Vol.l. Issue 8054. P. 31-34. 

Malathion is an organophosphate cholinesterase inhibitor. Up to 8% of the topically applied dose may be absorbed. Malathion is used as a treatment for head lice, body lice and scabies. It effectively kills both the eggs and the adult lice. Malathion is an insecticide of relatively low human toxicity. However if malathion is used in an indoor environment, as it breaks down into malaoxon, it can be seriously and chronically poisonous. The safety of malathion in pregnancy and in lactating women and in children has not been established. 

It is indicated as antidote for organo-phosphorus poisoning like malathion, TEPP, parathion etc. 

Esterase activity is important in both the detoxication of organophosphates and the toxicity caused by them. Thus brain acetylcholinesterase is inhibited by organophosphates such as paraoxon and malaoxon, their oxidized metabolites (see above). This leads to toxic effects. Malathion, a widely used insecticide, is metabolized mostly by carboxylesterase in mammals, and this is a route of detoxication. However, an isomer, isomalathion, formed from malathion when solutions are inappropriately stored, is a potent inhibitor of the carboxylesterase. The consequence is that such contaminated malathion becomes highly toxic to humans because detoxication is inhibited and oxidation becomes important. This led to the poisoning of 2800 workers in Pakistan and the death of 5 (see chap. 5 for metabolism and chap. 7 for more details). 

Endosulfan is used as an insecticide and as a contact poison. It is used primarily on food crops, cereals, tea, coffee, fruits, and vegetables. It is also used as a wood preservative. It is compatible with many other pesticides and may be found in formulations with dimethoate, malathion, methomyl, monocrotofos, pirimicarb, triazophos, fenoprop, parathion, petroleum oils, and oxine copper. It is not compatible with alkaline materials.14... 

E.L. Baker, Epidemic malathion poisoning in Pakistan malaria workers. Lancet 1 31, 1956. 

Amount of malathion estimated in different biological materials from poison cases, (from Lewin, et. al.(6)). 

There is a vast chemistry of organophosphorus compounds, and even for arsenic, antimony, and bismuth, the literature is voluminous. Consequently only a few topics can be discussed here. It must also be noted that we discuss only the compounds that have P—C bonds. Many compounds sometimes referred to as organophosphorus compounds that are widely used as insecticides, nerve poisons, and so on, as a result of their anticholinesterase activity, do not, in general, contain P—C bonds. They are usually organic esters of phosphates or thiophosphates examples are the well-known malathion and parathion, (EtO)2Pv(S)(0C6H4NO2). Compounds with P—C bonds are almost entirely synthetic, though a few rare examples occur in Nature. 

Although our military experience managing toxicity from nerve agent exposure is limited, exposures to related chemicals such as the OP class occur commonly each year in the USA. In 2006, there were a total of approximately 5,400 OP exposures across the USA (Bronstein et al, 2007). OPs, such as malathion, are commonly used as pesticides. OP toxicity manifests in a similar fashion as toxicity from nerve agents however, this chemical class is considerably less toxic. One case series of 16 children who experienced poisonings with OPs confirmed that pediatric patients present with toxicity differently than adults (Lifshitz et al, 1999). These children often did not manifest the classic muscarinic effects (such as salivary secretions and diarrhea) seen in adults. 

Kusic et al. (1991) have tested the oxime HI-6 in OP pesticide poisoning in 60 patients. HI-6 was administered four times a day as a single i.m. injection of 500 mg with atropine and diazepam treatment. Oxime therapy was started on admission and continued for 2 to 7 days. Most patients were treated with HI-6 and nine patients severely poisoned with quinalphos were treated 2-PAM Cl (1,000 mg four times per day). HI-6 rapidly reactivated human red blood cell AChE inhibited by diethoxy OPs (phorate, pyr-idaphenthion, quinalphos) as well as that inhibited by dichlorvos (a dimethoxy OP). AChE inhibited with other dimethoxy OPs (dimethoate and phosphamidon) was reported to be resistant to HI-6 treatment, whereas reactivation with malathion was slow (reactivation half-time 10 h). Both HI-6 and 2-PAM successfully reactivated AChE in quinalphos-poisoned patients, with HI-6 acting as a faster AChE reactivator than 2-PAM. 

NIOSH REL (Malathion) TWA 15 mg/m SAFETY PROFILE A human poison by ingestion and skin contact. Can penetrate intact skin. An experimental poison by ingestion, inhalation, intraperitoneal, intravenous, intraarterial, and subcutaneous routes. Human systemic effects by ingestion coma, blood pressure depression, and difficulty in breathing. Questionable... 

The organophosphosphates represent another extremely important class of organic insecticides. They were developed during World War II as chemical warfare agents. Early examples included the powerful insecticide schradan, a systemic insecticide, and the contact insecticide parathion. Unfortunately, both of these compounds are highly poisonous to mammals and subsequent research in this field has been directed toward the development of more selective and less poisonous insecticides. In 1950, malathion, the first example of a wide-specUnm organophosphorus insecticide combined with very low mammalian toxicity, was developed. And at about the same time the phenoxyacetic acid herbicides were discovered. These systemic compounds ate extremely valuable for the selective control of broad-leaved weeds in cereal crops. These compounds have a relatively low toxicity to mammals and are therefore relatively safe to use. 

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