Dichlorvos toxicity

Rider JA, Moeller HC, Puletti EJ. 1967. Continuing studies on anticholinesterase effect of methyl parathion, initial studies with guthion, and determination of incipient toxicity level of dichlorvos in humans [Abstract]. Fed Proc 26 427. 

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. 

Insecticides of the phosphoric acid triester class include paraoxon (9.49) and dichlorvos (9.50). The phosphorothioate derivative parathion is a relatively non-toxic insecticide that undergoes monooxygenase-catalyzed oxidative desulfuration to paraoxon [105] (see also Chapt. 7 in [59] see Sect. 9.3.6). Paraoxon itself, like its congeners and the P-halide nerve gases, is highly toxic through its potent inactivation of acetylcholinesterase [69]. 

It is used in swine in a single oral administration with feed at a dosage of 7.5-35 mg/kg bw for control of internal and external parasites. Although its anthelminthic spectfum is acceptable in cattle (38) and sheep (39), dichlorvos does not have FDA approval for use in ruminants due to its narrow safety margin. Also, dichlorvos cannot be used in poultry because birds accumulate the resin pellets in their gizzard. Dichlorvos is generally toxic to animals, and it is less toxic via the dermal and oral routes than by parenteral routes. Moreover, dichlorvos is a suspect carcinogen. 

Following oral administration to animals, dichlorvos is rapidly absorbed from the digestive tract and extensively metabolized in the liver. The metabolism of dichlorvos has not been clearly elucidated because almost none of its potential metabolites has been yet unequivocally identified due mainly to its very rapid biotransformation rate (6). It appears, however, that the initial hydrolysis of dichlorvos, which occurs in all species, leads presumably to dichloroacetaldehyde (40), which is further metabolized by reduction to dichloroethanol or oxidation to dichloroacetic acid. In addition, dealkylation to desmethyldichlorvos appears to be another minor route of biotransformation, except in the mouse where desmethyldichlorvos constitutes at least 18% of the administered radioactivity. The metabolites of dichlorvos do not persist in tissues, whereas only trace levels occur in the milk of lactating mammals (41). There is no evidence tliat the metabolites of dichlorvos are toxic. 

Trichlorphon is a precursor of dichlorvos used in swine and horses against gastrointestinal nematodes at dosages of 40-50 mg/kg bw. It is metabolized rapidly to dichlorvos, which is responsible for its therapeutic efficacy. The toxicity of trichlorphon is similar to that of dichlorvos. 

T. Purshottam, and R.K. Srivatsava, Effects of high-fat and high-protein diets on toxicity of parathion and dichlorvos. Arch. Environ. Health. 39 425, 1984. 

T ichlorvos (DDVP, dichlorovinyldimethyl phosphate) was first syn-thesized in the late 1940s, but active investigation of its insecticidal properties was not initiated until 1954. Investigations at that time revealed that low concentrations of the vapor of dichlorvos were toxic to adult mosquitoes and flies and that there appeared to be a relatively wide margin of safety between the insecticidal dose and the concentration required to affect man. 

Sterri, S.H. 1981. Factors modifying the toxicity of organophosphorous compounds including dichlorvos. Acta Pharmacol. Toxicol. 49 67-71. (cited in Somani et al., 1992)... 

Since 1917, only 11 new endoparasiticides have been developed for use in the horse. Many of the early compounds had very narrow spectra of activity and/or high potential for toxicity such that they have become obsolete. Febantel, levamisole, trichlorfon, dichlorvos, phenothiazine and carbon disulfide are no longer used routinely in the horse (Lyons et al 1999). 

The toxicity of dichlorvos is due to inhibition of acetylcholinesterase and the signs of toxicity are generally similar to those caused by other organo-phosphorus insecticides. Dichlorvos is a direct inhibitor of cholinesterases thus, toxicity rapidly follows exposure and recovery is also rapid. With inhalation exposures, airway acetylcholinesterase inhibition is possible in the absence of significant blood enzyme inhibition. The fly head acetylcholinesterase appears more sensitive to inhibition by dichlorvos relative to mammalian brain acetylcholinesterase. At high doses, dichlorvos may cause hyperglycemia and abnormal glucose tolerance. 

Dichlorvos is of moderate acute toxicity, with an oral LD50 value in rodents from 50 to 150mgkg. While the LC50 for inhibiting mammalian brain acetylcholinesterase is similar between dichlorvos and paraoxon (i.e., the active metabolite of parathion), the acute LD50 values for these agents are considerably different, due in part to the more rapid metabolism and elimination of dichlorvos. 

Inhalation, dermal, or oral exposure to dichlorvos can result in systemic toxicity through inhibition of acetylcholinesterase. Symptoms of acute exposure to dichlorvos may include blurred vision, nausea, headache, and shortness of breath. 

Dichlorvos is only slightly toxic to plants. Dichlorvos is moderately toxic to fish and highly toxic to aquatic invertebrates. However, in the presence of UV light, toxicity of dichlorvos to aquatic organisms can be increased 5-150-fold. It does not bioaccumulate in fish. The toxicity of dichlorvos to birds and mammals ranges from low to moderate. Dichlorvos is highly toxic to bees. Dichlorvos can be hazardous to endangered species. 

Trichlorfon has a low mammalian toxicity. Dichlorvos is more toxic, but the difference in toxicity between insects and vertebrates is very high. It evaporates easily and may be formulated in plastic strips that slowly release the insecticide, killing the insects, but it is apparently harmless to humans. The two compounds have also been widely used to kill salmon ectoparasites, as well as parasites encountered in veterinary medicine. However, they are strong teratogens in some species, disturbing brain development (Mehl et al., 2000), and should therefore be used with care. 

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