Malathion, toxicity

In addition to ester bonds with P (Section 10.2.1, Figures 10.1 and 10.2), some OPs have other ester bonds not involving P, which are readily broken by esteratic hydrolysis to bring about a loss of toxicity. Examples include the two carboxylester bonds of malathion, and the amido bond of dimethoate (Figure 10.2). The two carboxylester bonds of malathion can be cleaved by B-esterase attack, a conversion that provides the basis for the marked selectivity of this compound. Most insects lack an effective carboxylesterase, and for them malathion is highly toxic. Mammals and certain resistant insects, however, possess forms of carboxylesterase that rapidly hydrolyze these bonds, and are accordingly insensitive to malathion toxicity. 

Johnston, G.O., Collett, G., and Walker, C.H. et al. (1989). Enhancement of malathion toxicity in the hybrid red-legged partridge following exposure to prochloraz. Pesticide Biochemistry and Physiology 35, 107-118. 

Hermanutz R. 1978. Endrin and malathion toxicity to flagfish (Jordanella floridae). Arch Environ Contain Toxicol 7 159-168. 

The term potentiation is then reserved for those cases where both compounds have appreciable intrinsic toxicity, such as in the case of malathion and EPN. Malathion has a low mammalian toxicity due primarily to its rapid hydrolysis by a carboxylesterase. EPN (Figure 9.6) another organophosphate insecticide, causes a dramatic increase in malathion toxicity to mammals at dose levels, which, given alone, cause essentially no inhibition of acetylcholinesterase. The increase in toxicity as a result of coadministration of these two toxicants is the result of the ability of EPN, at low concentrations, to inhibit the carboxylesterase responsible for malathion degradation. 

Hermanutz, R.O. (1978) Endrin and malathion toxicity to flagfish (Jordanella floridae). Arch. Environ. Contam. Toxicol. 7, 159-168. Hermens, J., Leeuwangh, P. (1982) Joint toxicity of mixture of 8 and 24 chemicals to the guppy (Poecilia reticulata). Ecotoxicol. Environ. Saf. 6, 302-310. 

The toxicity of organophosphates or carbamates can be potentiated several-fold if the activity of CarbE is inhibited by pretreatment. Potentiation of malathion toxicity by EPN (O-ethyl-O-p-nitrophenyl phenyl-phosphonothionate) was reported about half a century... 

Venturino A, Gauna LE, Bergoc RM. Effect of exogenously applied polyamine on malathion toxicity in the toad Bufo arenarum Hensel. Arch Environ Contain Toxicol 1992 22(1) 135-9. 

Kuperman, R.G., Simini, M., Phillips, C.T. and Checkai, R.T. (1999) Comparison of malathion toxicity using enchytraeid reproduction test and earthworm toxicity test in different soil types. Pedobiologia, 43, 630-634. 

The development of malathion in 1950 was an important milestone in the emergence of selective insecticides. Malathion is from one-half to one-twentieth as toxic to insects as parathion but is only about one two-hundredths as toxic to mammals. Its worldwide usage in quantities of thousands of metric tons in the home, garden, field, orchard, woodland, on animals, and in pubHc health programs has demonstrated substantial safety coupled with pest control effectiveness. The biochemical basis for the selectivity of malathion is its rapid detoxication in the mammalian Hver, but not in the insect, through the attack of carboxyesterase enzymes on the aUphatic ester moieties of the molecule. 

Methylparathion is the corresponding dimethyl derivative. Later (1952) malathion found favour because of its decreased toxicity to mammals it is readily made in 90% yield by the addition of dimethyidithiophosphate to diethylmaleate in the presence of NEtr as a cataly.st and hydroquinone as a polymerization inhibitor ... 

As noted earlier, OPs are known to be highly toxic to aquatic invertebrates and to fish. This has been demonstrated in field studies. For example, malathion applied to watercress beds caused lethal intoxication of the freshwater shrimp Gammarus pulex located downstream (Crane et al. 1995). Kills of marine invertebrates have been reported following the application of OPs. Accidental release of OPs into rivers, lakes, and bays has sometimes caused large-scale fish kills (see Environmental Health Criteria 63). 

As Muller had prophesied and indeed hoped, DDT stimulated the discovery of more synthetic insecticides. DDT relatives included chlordane, toxaphene, aldrin, dieldrin, endrin, and heptachlor. Popular substitutes for DDT s family included organophosphates such as parathion, which is a powerful neurotoxin, and carbamates, which are also highly toxic to people. Unlike DDT, parathion and aldicarb have killed and injured many farm workers. Malathion was later developed to be several hundred times less toxic than parathion. 

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. 

There is a significant amount of data from other countries on the effects on human health of large-scale pesticide production and use, in particular of OPPs and OCPs. Even one-time, accidental contact with some OCPs and OPPs such as dieldrin, malathion, and parathion, can lead to changes in the encephalogram (which remain for a year after exposure), disruptions of sleep patterns and memory, loss of libido, and difficulties in concentration [3]. Global practice shows that all pesticides are toxic to humans. 

Even though all OP insecticides have a common mechanism of action, differences occur among individual compounds. OP insecticides can be grouped into direct and indirect ACHE inhibitors. Direct inhibitors are effective without any metabolic modification, while indirect inhibitors require biotransformation to be effective. Moreover, some OP pesticides inhibit ACHE more than PCHE, while others do the opposite. For example, malathion, diazinon, and dichlorvos are earlier inhibitors of PCHE than of ACHE. In these cases, PCHE is a more sensitive indicator of exposure, even though it is not correlated with symptoms or signs of toxicity. 

In spite of their toxicity, alkyl phosphites have been used extensively as lubricant additives, corrosion inhibitors, and antioxidants. In addition to their use as intermediates in synthesis, organophosphorus compounds are useful for separating heavy metals by solvent extraction. Several insecticides that were formerly in widespread use are derivatives of organic phosphates. Two such compounds are malathion and parathion. 

The toxicity of an insecticide not only depends upon its molecular structure but also the way it is metabolised. A good example of this is Malathion (77), which is metabolised very differently by insects and humans and is therefore only toxic to insects. The mildly active Malathion (77) is rapidly oxidised in insects converting it into the strongly active oxidation product 79 (Equation 84), and this is only broken down very slowly by hydrolysis to give the weakly active 81. In contrast, oxidation of Malathion in mammals is slow, but hydrolysis of the ester group occurs very rapidly to give the inactive non-toxic compound 80 (Equation 84).1,169... 

According to the results obtained, and assuming that the simple additive approach applied is valid, malathion appears to be the main contributor to Daphnia toxicity (98% toxic contribution on average for all samples) molinate, fenitrothion, and malathion would be the most relevant pesticides in the case of V. fischeri... 

In all cases, the concentrations of malathion and fenitrothion measured in water (up to 5.8 and 1.2 pg/L, respectively) were below the LC50 (lethal concentration 50%) values reported for these compounds in oysters and mussels, which range between 2.7 and 278 mg/L in the case of malathion, and between 10.3 pg/L and 123 mg/L in the case of fenitrothion (http //www.pesticideinfo.org). However, it has to be stressed that these LC50 values express acute toxicity, that both malathion and fenitrothion might be bioaccumulated by molluscs (as their detection in biota suggests), and that aquatic organisms are exposed to a variety of contaminants, some of which could show synergetic or additive effects [40]. Further matters of... 

---