Inhibitor Report for: Dioxathion

In a four year survey 253 isolates of Boophilus decoloratus from the Republic of South Africa and Transkei were tested in the laboratory for their susceptibility to certain organophosphorus ixodicides. Fifty-seven of these isolates were susceptible to organophosphorus compounds, 88 isolates showed a range of susceptibility between that of the susceptible laboratory strain and a strain having a resistance greater than that for the Berlin type strain. A field trial confirmed degrees of resistance shown in the laboratory to the organophosphorus ixodicides benoxophos, chlorfenvinphos, dioxathion, dicrotophos, quintiofos and chlorfenvinphos/dioxathion.

A series of in vitro trails confirmed resistance in the three-host tick, Amblyomma hebraeum Koch, to the organophosphorus ixodicides, dioxathion, chlorfenvinphos, quintiofos, bromophos-ethyl and a dioxathion/chlorfenvinphos combination. The results of a routine survey showed that a resistance factor of greater than 100x was present in the offspring of ticks in six of 115 field isolates tested. These six isolates were confined to the lowveld areas of the province of Natal, Republic of South Africa, and Swaziland. Ticks in a further 59 isolates were less susceptible than the reference strain. Resistance was present in all three tick instars. This is the first recorded resistance to the organophosphorus group of ixodicides by multi-host ticks in Africa.

The M2 subtype of muscarinic receptor is predominant in heart, and such receptors were reported to be located in muscles as well as in presynaptic cholinergic and adrenergic nerve terminals. Muscarinic receptors of rat heart were identified by the high affinity binding of the agonist (+)-[3H]cis-methyldioxolane ([3H]CD), which has been used to label a high affinity population of M2 receptors. A single population of sites (KD 2.74 nM; Bmax of 82 fmol/mg protein) was detected and [3H]CD binding was sensitive to the M2 antagonist himbacine but much less so to pirenzepine, the M1 antagonist. These cardiac receptors had different sensitivities to NiCl2 and N-ethylmaleimide from brain muscarinic receptors, that were also labeled with [3H]CD and considered to be of the M2 subtype. Up to 70% of the [3H]CD-labeled cardiac receptors had high affinities for several organophosphate (OP) anticholinesterases. [3H]CD binding was inhibited by the nerve agents soman, VX, sarin, and tabun, with K0.5 values of 0.8, 2, 20, and 50 nM, respectively. It was also inhibited by echothiophate and paraoxon with K0.5 values of 100 and 300 nM, respectively. The apparent competitive nature of inhibition of [3H]CD binding by both sarin and paraoxon suggests that the OPs bind to the acetylcholine binding site of the muscarinic receptor. Other OP insecticides had lower potencies, inhibiting less than 50% of 5 nM [3H]CD binding by 1 microM of EPN, coumaphos, dioxathion, dichlorvos, or chlorpyriphos. There was poor correlation between the potencies of the OPs in reversibly inhibiting [3H]CD binding, and their anticholinesterase activities and toxicities. Acetylcholinesterases are the primary targets for these OP compounds because of the irreversible nature of their inhibition, which results in building of acetylcholine concentrations that activate muscarinic and nicotinic receptors and desensitize them, thereby inhibiting respiration. Nevertheless, the high affinities that cardiac muscarinic receptors have for these toxicants point to their extra vulnerability. It is suggested that the success of iv administration of the muscarinic receptor inhibitor atropine in initial therapy of poisoning by OP anticholinesterases may be related in part to the extra sensitivity of M2 receptors to certain OPs.

A strain of Boophilus decoloratus, resistant to fenvalerate, was subjected to larval immersion, adult immersion and stall tests using the following classes of ixodicides: organochlorines, organophosphates, a diamidide and pyrethroids. A susceptible reference strain of B. decoloratus was used for comparative purposes. The results indicated a high level of resistance to DDT and camphechlor, slight tolerance to dioxathion, chlorfenvinphos and pirimiphos ethyl, full susceptibility to bromophos ethyl and amitraz, but marked resistance to cyhalothrin, cypemethrin, deltamethrin and flumethrin. This marked resistance in the strain therefore appears to be widespread within the pyrethroid group of chemicals and may have developed as a result of organochlorine cross-resistance.

A series of in vitro trials using unfed larvae and fully fed adult ticks confirmed ixodicidal resistance in the one-host Pantropical Blue Tick, Boophilus microplus (Canestrini). Fifty-seven of 64 field isolates were resistant to arsenic; 10 of 56 were resistant to toxaphene; 1 of 5 were resistant to lindane; 3 of 5 were resistant to dieldrin; 3 of 19 were resistant to DDT and 8 of 55 were resistant to the organophosphorus ixodicide, dioxathion. One of the field isolates resistant to dioxathion was also highly resistant to the carbamate, carbaryl, and to the organophosphorus ixodicides benoxophos and diazinon. A second was resistant to the organophosphorus ixodicides benoxophos, diazinon, carbophenothion, dicrotophos, ethion, fenitrothion and quintiofos. Low levels of resistance, less than 3X, were shown to chlorfenvinphos and coumaphos. No resistance was shown to chlorpyrifos, bromophos ethyl or the diamidine ixodicide, amitraz. In hand-spraying trials no variation in the susceptibility of an organophosphorus resistant strain or the susceptible laboratory strain to amitraz was observed. This is the first recorded resistance to ixodicides by B. microplus in Africa.

Doses of ten acaricides, ranging from 2.5 to 10 ug, induced about 10-60% mortality and inhibited oviposition in engorged Boophilus microplus as well as preventing larval hatching from the eggs. The effects of the acaricides were dose dependent. The efficacy of acaricides in reducing the reproductive potential (inhibition of oviposition inhibition of hatching/100) was in the following order: dimethoate > dioxathion > naled > diazinon > chlordimeform > carbaryl > trichlorphon > phosphamidon > gamma-HCH > fenitrothion. Most of the acaricides also retarded the oviposition cycle, delaying the peak activity by 4-8 days. The ovarian development in control ticks reached its peak between the 5th and 7th days before decreasing gradually and ceasing completely between the 16-20th days after engorgement. The protein content of the ovaries and the rate of incorporation of [14C]glycine into the tissues followed a similar pattern. Carbaryl, fenitrothion and naled inhibited these activities. Chlordimeform stimulated [14C]glycine incorporation and increased the ovarian protein content up to the 13th day before resorption of the oocytes. The eggs from treated ticks were mostly non-viable and contained more protein; those from dioxathion, carbaryl and chlordimeform treatments had a higher dry weight than the control.

In a four year survey 253 isolates of Boophilus decoloratus from the Republic of South Africa and Transkei were tested in the laboratory for their susceptibility to certain organophosphorus ixodicides. Fifty-seven of these isolates were susceptible to organophosphorus compounds, 88 isolates showed a range of susceptibility between that of the susceptible laboratory strain and a strain having a resistance greater than that for the Berlin type strain. A field trial confirmed degrees of resistance shown in the laboratory to the organophosphorus ixodicides benoxophos, chlorfenvinphos, dioxathion, dicrotophos, quintiofos and chlorfenvinphos/dioxathion.

A series of in vitro trails confirmed resistance in the three-host tick, Amblyomma hebraeum Koch, to the organophosphorus ixodicides, dioxathion, chlorfenvinphos, quintiofos, bromophos-ethyl and a dioxathion/chlorfenvinphos combination. The results of a routine survey showed that a resistance factor of greater than 100x was present in the offspring of ticks in six of 115 field isolates tested. These six isolates were confined to the lowveld areas of the province of Natal, Republic of South Africa, and Swaziland. Ticks in a further 59 isolates were less susceptible than the reference strain. Resistance was present in all three tick instars. This is the first recorded resistance to the organophosphorus group of ixodicides by multi-host ticks in Africa.