Inhibitor Report for: Methylchlorpyrifos

During Fiscal Years 1989-1994, the U.S. Food and Drug Administration (FDA) collected and analyzed 545 domestic surveillance samples of mixed feed rations (172 for cattle, 125 for poultry, 83 for swine, 61 for pets, 56 for fish, and 48 miscellaneous). All samples were analyzed by gas-liquid chromatography for organohalogen and organophosphorus pesticides. Of the 545 samples, 88 (16.1%) did not contain detectable pesticide residues. In the 457 samples with detectable pesticide levels, 804 residues (654 quantitable and 150 trace) were found. None of these 804 residues exceeded regulatory guidance. Malathion, chlorpyrifos-methyl, diazinon, chlorpyrifos, and pirimiphos-methyl were the most commonly detected pesticides. These 5 organophosphorus pesticides accounted for 93.4% of all pesticide residues detected (malathion, 52.9%; chlorpyrifos-methyl, 25.2%; diazinon, 7.7%; chlorpyrifos, 4.9%; and pirimiphos-methyl, 2.7%). Their median values in samples containing quantitable levels ranged from 0.014 to 0.098 ppm. The most commonly detected organohalogen compounds were methoxychlor, DDE, PCB, dieldrin, pentachloronitrobenzene, and lindane. These 6 compounds combined accounted for only 4.1% of all residues detected. FDA is continuing its pesticide surveillance of feeds to help ensure animal safety and prevent violative residues in food derived from animals.

The acute toxicity of chlorpyrifos, methylchlorpyrifos, parathion and methylparathion to three age classes of Artemia salina was determined. In general, A. salina 24-h old was less sensitive to these organophosphorous insecticides (OPI) than A. salina 48-h old and A. salina 48-h old was significantly more tolerant than A. salina 72-h old, in contrast, chlorpyrifos was equally toxic to A. salina 48- and 72-h old. There were some differences among the three age classes of A. salina in the relative order of toxicity of OPI tested. The rank order of toxicity to A. salina 48-h old was methylparathion < parathion < methyl-chlorpyrifos < chlorpyrifos, while to A. salina 24- and 72-h old it was methylparathion = parathion < methyl-chlorpyrifos < chlorpyrifos. The protective effect of the cholinergic antagonists atropine, hexamethonium, pirenzepine and 11-(2-((diethyl-amino)methyl)-1-piperidinylacetyl)-5, 11-dihydro-6H-pyrido(2,3-b)-(1,4)-benzodiazepine-6-one (AF-DX 116) and a cholinesterase-reactivating oxime 2-pyridine aldoxime methochloride (2-PAM) on the mortality due to four selected OPI in Artemia salina 24-h old was investigated. The lethal action of OPI tested was completely prevented by pretreatment of Artemia salina 24-h old with 2-PAM (10(-5) M) and atropine (10(-4 )M). However no concentration of hexamethonium, pirenzepine or AF-DX 116 protected 100% of the animals poisoned by LC84 of the OPI selected, maximum protection obtained was 71 to 88%. In contrast, the maximum inhibition of mortality obtained with AF-DX 116 pretreatment was about 55% because this compound was used at concentrations which were non toxic to control Artemia salina. Atropine, hexamethonium, pirenzepine, AF-DX 116 and 2-PAM afforded 50 % protection (IC50) of Artemia salina against mortality by LC84 of the OPI selected at concentrations in the range of 6.62x10(-7)-1.6x10(-6) M, 2. 38x10(-4)-2.05x10(-3)M, 8.91x10(-7)-1.24x10(-6) M, 9.66x10(-8)-1. 34x10(-7 )M, and 1.95x10(-8)-2.73x10(-8 )M, respectively. Pretreatment of atropine plus 2-PAM to determine whether this combination afforded greater inhibition of the lethality induced by four OPI tested than pretreatment with either atropine or 2-PAM alone was investigated. Atropine (10(-5) M) in combination with 2-PAM (10(-7 )M) inhibited completely the acute toxicity of all OPI tested, while the pretreatment with atropine (10(-6) M) plus 2-PAM at the same concentration gave a inhibition of mortality (about 62%) significantly greater than each antagonist alone (about 14 and 46%, respectively).

Before beginning a widespread control program against Culex pipiens quinquefasciatus in Martinique, resistance to temephos, chlorpyrifos, and two organophosphorous insecticides, was investigated at seven breeding sites. At LC95, populations exhibited resistance ratios between 6.9 and 11.6 for temephos and between 6.4 and 51.4 for chlorpyrifos. Overproduced esterases A2-B2 and B1, known to be involved in organophosphorous-resistance, were present at all breeding sites; esterases A2-B2 frequency was > 50% at all sites but one; and esterase B1 frequency was < 7%. Experimental treatment of three breeding sites with temephos induced no significant increase in resistance, but our esterase studies indicated a significant increase in the frequencies of esterase B1 and of a new highly active esterase C2. These results indicate that a large-scale C. p. quinquefasciatus control program with organophosphorous insecticides will induce a rapid increase of these resistance genes throughout Martinique. However, this may not necessarily result in high levels of resistance, because, at present, the level of gene amplification of esterase B still appears to be low.