Paper(s) concerning Chlorpyrifos59 reference(s) found.
Szafran BN, Nichols J, Nicaise A, Borazjani A, Carr R, Wilson JR, Ross MK, Kaplan BLF Ref: Chemico-Biological Interactions, :110425, 2023 : PubMed ESTHER: Szafran_2023_Chem.Biol.Interact__110425 PubMedSearch: Szafran 2023 Chem.Biol.Interact 110425 PubMedID: 36858108 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Chlorpyrifos (CPF) is an organophosphate pesticide that can inhibit endocannabinoid (eCB) metabolizing enzymes in animal models at levels that do not significantly alter acetylcholinesterase (AChE) in the central nervous system. Previous studies indicated that repeated low-level CPF exposure in developing rats increased the levels of eCBs in the brain. Because eCBs play a role in immune homeostasis through their engagement with cannabinoid receptors, we investigated the role of cannabinoid receptor 1 (CB1, encoded by the Cnr1 gene) on the CPF-mediated effects in the spleen and lung of neonatal and adult female mice. We treated neonatal and adult female Cnr1(-/-) mice with 2.5 mg/kg oral CPF or vehicle for 7 days. Tissues were harvested 4 h after the last CPF dose to evaluate eCB metabolic enzyme activity, levels of eCBs, and tissue immunophenotype. There were a small number of genotype-dependent alterations noted in the endpoints following CPF treatment that were specific to age and tissue type, and differences in eCB metabolism caused by CPF treatment did not correlate to changes in eCB levels. To explore the role of CB1 in CPF-mediated effects on immune endpoints, in vitro experiments were performed with WT murine splenocytes exposed to chlorpyrifos oxon (CPO; oxon metabolite of CPF) and challenged with lipopolysaccharide (LPS). While CPO did not alter LPS-induced pro-inflammatory cytokine levels, inactivation of CB1 by the antagonist SR141716A augmented LPS-induced IFN-gamma levels. Additional experiments with WT and Cnr1(-/-) murine splenocytes confirmed a role for CB1 in altering the production of LPS-induced pro-inflammatory cytokine levels. We conclude that CPF-mediated effects on the eCB system are not strongly dependent on CB1, although abrogation of CB1 does alter LPS-induced cytokine levels in splenocytes. Title: Effects of chlorpyrifos on transient receptor potential channels Li W, Ehrich M Ref: Toxicol Lett, 358:100, 2022 : PubMed ESTHER: Li_2022_Toxicol.Lett_358_100 PubMedSearch: Li 2022 Toxicol.Lett 358 100 PubMedID: 35114315 Inhibitor(s) related to this paper: Chlorpyrifos Abstract The well-known toxicity of chlorpyrifos (CPF) occurs via inhibition of cholinesterase (ChE), but in recent years the detrimental effects of low-dose CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We previously showed that CPF can alter gene expression of transient receptor potential canonical (TRPC) channels in vitro. In this study, we analyzed the gene expression of TRPCs at various time points after CPF treatment in vivo. The results showed that TRPC1 mRNA expression in mouse brain was significantly reduced 2-8 h after CPF treatment, but the TRPC4 mRNA expression was not significantly changed. To investigate the possible involvement of Transforming Growth Factor-beta1 (TGF-beta1) in contributing to TRPCs gene alteration by CPF, we used TGF-beta receptor inhibitor (LY2109761) as a pretreatment prior to CPF treatment. The serum TGF-beta1 concentration was significantly increased 24 h after CPF treatment. After pretreatment with LY2109761, both TRPC1 and TRPC5 mRNAs were significantly downregulated 1 and 2 h after CPF treatment, but were significantly upregulated 3 and 24 h after CPF treatment. TRPC4 mRNA was also significantly downregulated at 1 h. These results suggest that interference with ion channels, a non-cholinergic mechanism of CPF, may contribute to the cellular neurotoxicity of CPF. Title: Inhibition of Serum Esterases in Juvenile Rats Repeatedly Exposed to Low Levels of Chlorpyrifos Mosier JA, Hybart RL, Lewis AM, Carr RL Ref: Int J Sci Res Environ Sci Toxicol, 5:1, 2022 : PubMed ESTHER: Mosier_2022_Int.J.Sc.Res.Environ.Sci.Toxicol_5_1 PubMedSearch: Mosier 2022 Int.J.Sc.Res.Environ.Sci.Toxicol 5 1 Inhibitor(s) related to this paper: Chlorpyrifos Abstract developmental exposure. While the canonical mechanism of toxicity of CPF involves the inhibition of brain acetylcholinesterase (AChE), we have reported that exposure of juvenile rats to levels of CPF that do not yield any inhibition of brain AChE results in neurobehavioral alterations at later ages. However, it is unclear what effect exposure to these low levels of CPF has on blood esterase activities which are frequently used not only as biomarkers of exposure but also to set exposure levels in risk assessment. To determine this, male and female rat pups were exposed orally from postnatal day 10 to 16 to either corn oil (vehicle) or 0.5, 0.75, or 1.0 mg/kg CPF. At 12 h after the final exposure, serum cholinesterase (ChE), butyrylcholinesterase (BChE), and carboxylesterase (CES), and red blood cell (RBC) and brain AChE activities were determined. There were no differences between sexes in either the controls or individual treatments for all enzymes. Only the highest dosage of 1.0 mg/kg CPF yielded significant brain AChE inhibition (22-24%) but all dosages significantly inhibited the blood esterases with inhibition being highest with serum CES (65-85%) followed by serum BChE (57-76%), RBC AChE (35-65%), and then serum ChE (16-32%). Our data verify that blood esterases are inhibited at dosages of CPF that alter neurobehavioral performance in the absence of effects on brain AChE activity. Title: Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development Carr RL, Armstrong NH, Buchanan AT, Eells JB, Mohammed AN, Ross MK, Nail CA Ref: Neurotoxicology, 59:183, 2017 : PubMed ESTHER: Carr_2017_Neurotoxicol_59_183 PubMedSearch: Carr 2017 Neurotoxicol 59 183 PubMedID: 26642910 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Exposure to chlorpyrifos (CPF) during the late preweanling period in rats inhibits the endocannabinoid metabolizing enzymes fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL), resulting in accumulation of their respective substrates anandamide (AEA) and 2-arachidonylglycerol (2-AG). This occurs at 1.0mg/kg, but at a lower dosage (0.5mg/kg) only FAAH and AEA are affected with no measurable inhibition of either cholinesterase (ChE) or MAGL. The endocannabinoid system plays a vital role in nervous system development and may be an important developmental target for CPF. The endocannabinoid system plays an important role in the regulation of anxiety and, at higher dosages, developmental exposure to CPF alters anxiety-like behavior. However, it is not clear whether exposure to low dosages of CPF that do not inhibit ChE will cause any persistent effects on anxiety-like behavior. To determine if this occurs, 10-day old rat pups were exposed daily for 7 days to either corn oil or 0.5, 0.75, or 1.0mg/kg CPF by oral gavage. At 12h following the last CPF administration, 1.0mg/kg resulted in significant inhibition of FAAH, MAGL, and ChE, whereas 0.5 and 0.75mg/kg resulted in significant inhibition of only FAAH. AEA levels were significantly elevated in all three treatment groups as were palmitoylethanolamide and oleoylethanolamide, which are also substrates for FAAH. 2-AG levels were significantly elevated by 0.75 and 1.0mg/kg but not 0.5mg/kg. On day 25, the latency to emerge from a dark container into a highly illuminated novel open field was measured as an indicator of anxiety. All three CPF treatment groups spent significantly less time in the dark container prior to emerging as compared to the control group, suggesting a decreased level of anxiety. This demonstrates that repeated preweanling exposure to dosages of CPF that do not inhibit brain ChE can induce a decline in the level of anxiety that is detectable during the early postweanling period. Title: Exploration of the chlorpyrifos escape pathway from acylpeptide hydrolases using steered molecular dynamics simulations Wang D, Jin H, Wang J, Guan S, Zhang Z, Han W Ref: J Biomol Struct Dyn, 34:749, 2016 : PubMed ESTHER: Wang_2016_J.Biomol.Struct.Dyn_34_749 PubMedSearch: Wang 2016 J.Biomol.Struct.Dyn 34 749 PubMedID: 26155973 Gene_locus related to this paper: aerpe-APE1547 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Acylpeptide hydrolases (APH) catalyze the removal of an N-acylated amino acid from blocked peptides. APH is significantly more sensitive than acetylcholinesterase, a target of Alzheimer's disease, to inhibition by organophosphorus (OP) compounds. Thus, OP compounds can be used as a tool to probe the physiological functions of APH. Here, we report the results of a computational study of molecular dynamics simulations of APH bound to the OP compounds and an exploration of the chlorpyrifos escape pathway using steered molecular dynamics (SMD) simulations. In addition, we apply SMD simulations to identify potential escape routes of chlorpyrifos from hydrolase hydrophobic cavities in the APH-inhibitor complex. Two previously proposed APH pathways were reliably identified by CAVER 3.0, with the estimated relative importance of P1 > P2 for its size. We identify the major pathway, P2, using SMD simulations, and Arg526, Glu88, Gly86, and Asn65 are identified as important residues for the ligand leaving via P2. These results may help in the design of APH-targeting drugs with improved efficacy, as well as in understanding APH selectivity of the inhibitor binding in the prolyl oligopeptidase family. Title: Induction of endocannabinoid levels in juvenile rat brain following developmental chlorpyrifos exposure Carr RL, Adams AL, Kepler DR, Ward AB, Ross MK Ref: Toxicol Sci, 135:193, 2013 : PubMed ESTHER: Carr_2013_Toxicol.Sci_135_193 PubMedSearch: Carr 2013 Toxicol.Sci 135 193 PubMedID: 23761300 Inhibitor(s) related to this paper: Chlorpyrifos Abstract The endogenous cannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) play vital roles during nervous system development. The degradation of 2-AG and AEA is mediated by monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), respectively. These enzymes are inhibited following developmental chlorpyrifos (CPF) exposure. To investigate whether this inhibition is persistent or whether accumulation of endocannabinoids in the brain occurs, 10-day-old rat pups were orally exposed daily for 7 days to either corn oil or increasing dosages of CPF (1, 2.5, or 5mg/kg), and forebrains were collected at 4, 12, 24, and 48h following the last administration. All dosages inhibited cholinesterase (ChE), FAAH, and MAGL, and elevated AEA and 2-AG levels with the greatest effect occurring at 12h with ChE, FAAH, AEA, and 2-AG and at 4h with MAGL. With the high dosage, return to control levels occurred with 2-AG (48h) only. With the medium dosage, return to control levels occurred with MAGL, 2-AG, and AEA (48h) but not with ChE or FAAH. With the low dosage, return to control levels occurred with MAGL (12h), ChE and 2-AG (24h), and AEA (48h) but not with FAAH. With the lowest dosage, peak inhibition of FAAH (52%) is greater than that of ChE (24%) and that level of FAAH inhibition is sufficient to induce a persistent pattern of elevated AEA. It is possible that this pattern of elevation could alter the appropriate development of neuronal brain circuits. Title: Mice treated with chlorpyrifos or chlorpyrifos oxon have organophosphorylated tubulin in the brain and disrupted microtubule structures, suggesting a role for tubulin in neurotoxicity associated with exposure to organophosphorus agents Jiang W, Duysen EG, Hansen H, Shlyakhtenko L, Schopfer LM, Lockridge O Ref: Toxicol Sci, 115:183, 2010 : PubMed ESTHER: Jiang_2010_Toxicol.Sci_115_183 PubMedSearch: Jiang 2010 Toxicol.Sci 115 183 PubMedID: 20142434 Inhibitor(s) related to this paper: Chlorpyrifos, Chlorpyrifos-oxon Abstract Exposure to organophosphorus (OP) agents can lead to learning and memory deficits. Disruption of axonal transport has been proposed as a possible explanation. Microtubules are an essential component of axonal transport. In vitro studies have demonstrated that OP agents react with tubulin and disrupt the structure of microtubules. Our goal was to determine whether in vivo exposure affects microtubule structure. One group of mice was treated daily for 14 days with a dose of chlorpyrifos that did not significantly inhibit acetylcholinesterase. Beta-tubulin from the brains of these mice was diethoxyphosphorylated on tyrosine 281 in peptide GSQQY(281)RALTVPELTQQMFDSK. A second group of mice was treated with a single sublethal dose of chlorpyrifos oxon (CPO). Microtubules and cosedimenting proteins from the brains of these mice were visualized by atomic force microscopy nanoimaging and by Coomassie blue staining of polyacrylamide gel electrophoresis bands. Proteins in gel slices were identified by mass spectrometry. Nanoimaging showed that microtubules from control mice were decorated with many proteins, whereas microtubules from CPO-treated mice had fewer associated proteins, a result confirmed by mass spectrometry of proteins extracted from gel slices. The dimensions of microtubules from CPO-treated mice (height 8.7 +/- 3.1 nm and width 36.5 +/- 15.5 nm) were about 60% of those from control mice (height 13.6 +/- 3.6 nm and width 64.8 +/- 15.9 nm). A third group of mice was treated with six sublethal doses of CPO over 50.15 h. Mass spectrometry identified diethoxyphosphorylated serine 338 in peptide NS(338)NFVEWIPNNVK of beta-tubulin. In conclusion, microtubules from mice exposed to chlorpyrifos or to CPO have covalently modified amino acids and abnormal structure, suggesting disruption of microtubule function. Covalent binding of CPO to tubulin and to tubulin-associated proteins is a potential mechanism of neurotoxicity. Title: Cross-resistance and possible mechanisms of chlorpyrifos resistance in Laodelphax striatellus (Fallen) Wang L, Zhang Y, Han Z, Liu Y, Fang J Ref: Pest Manag Sci, 66:1096, 2010 : PubMed ESTHER: Wang_2010_Pest.Manag.Sci_66_1096 PubMedSearch: Wang 2010 Pest.Manag.Sci 66 1096 PubMedID: 20582994 Inhibitor(s) related to this paper: TPHP, Chlorpyrifos Abstract BACKGROUND: Laodelphax striatellus (Fallen) is a major pest of cultivated rice and is commonly controlled in China with the organophosphate insecticides. To develop a better resistance management strategy, a chlorpyrifos-resistant strain of L. striatellus was selected in the laboratory, and its cross-resistance to other insecticides and possible mechanisms of the chlorpyrifos resistance were investigated. RESULTS: After 25 generations of selection with chlorpyrifos, the selected strain of L. striatellus developed 188-fold resistance to chlorpyrifos in comparison with the susceptible strain, and showed 14- and 1.6-fold cross-resistance to dichlorvos and thiamethoxam respectively. There was no apparent cross-resistance to abamectin. Chlorpyrifos was synergised by the inhibitor triphenyl phosphate; the carboxylesterase synergistic ratio was 3.8 for the selected strain, but only 0.92 for the susceptible strain. The carboxylesterase activity of the selected strain was approximately 4 times that of the susceptible strain, whereas there was no significant change in the activities of alkaline phosphatase, acid phosphatase, glutathione S-transferase and cytochrome P450 monooxygenase between the strains. The Michaelis constant of acetylcholinesterase, maximum velocity of acetylcholinesterase and median inhibitory concentration of chlorpyrifos-oxon on acetylcholinesterase were 1.7, 2.5 and 5 times higher respectively in the selected strain. CONCLUSION: The high cross-resistance to the organophosphate dichlorvos in the chlorpyrifos-resistant strain suggests that other non-organophosphate insecticides would be necessary to counter resistance, should it arise in the field. Enhanced activities of carboxylesterase and the acetylcholinesterase insensitivity appear to be important mechanisms for chlorpyrifos resistance in L. striatellus. Title: Extremely sensitive biomarker of acute organophosphorus insecticide exposure Fujikawa Y, Satoh T, Suganuma A, Suzuki S, Niikura Y, Yui S, Yamaura Y Ref: Hum Exp Toxicol, 24:333, 2005 : PubMed ESTHER: Fujikawa_2005_Hum.Exp.Toxicol_24_333 PubMedSearch: Fujikawa 2005 Hum.Exp.Toxicol 24 333 PubMedID: 16004201 Gene_locus related to this paper: human-CES1, mouse-Ces1e, ratno-Ces1e Inhibitor(s) related to this paper: Acephate, Chlorpyrifos, EPN Abstract Egasyn-beta-glucuronidase complex is located at the luminal site of liver microsomal endoplasmic reticulum. When organophosphorus insecticides (OP) are incorporated into the liver microsomes, they become tightly bound to egasyn, a carboxylesterase isozyme, and subsequently, beta-glucuronidase (BG) is dissociated and released into blood. Consequently, the increase in plasma BG activity becomes a good biomarker of OP exposure. Thus, the single administration of EPN (O-ethyl O-p-nitrophenylphenylphosphonothioate), acephate and chlorpyrifos increased plasma BG activity in approximately 100-fold the control level in rats. The increase in plasma BG activity after OP exposure is a much more sensitive biomarker of acute OP exposure than acetylcholinesterase (AChE) inhibition. Title: Determination of the reference dose for chlorpyrifos: proceedings of an expert panel Clegg DJ, van Gemert M Ref: J Toxicol Environ Health B Crit Rev, 2:211, 1999 : PubMed ESTHER: Clegg_1999_J.Toxicol.Environ.Health.B.Crit.Rev_2_211 PubMedSearch: Clegg 1999 J.Toxicol.Environ.Health.B.Crit.Rev 2 211 PubMedID: 10429680 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Chlorpyrifos is an extensively used organophosphate insecticide with numerous agricultural crop and urban pest control uses. Dow AgroSciences, one of the manufacturers of chlorpyrifos, convened a panel of toxicology and medical experts to consider the available scientific literature (both published papers and unpublished reports from Dow AgroSciences) on chlorpyrifos with respect to determining the acute and chronic toxicological reference doses (RfD) for chlorpyrifos. The most sensitive effect observed in the body of animal and human studies on chlorpyrifos is the inhibition of the various cholinesterases. In animal studies chlorpyrifos is not carcinogenic, teratogenic, or mutagenic. Reproductive toxicity studies indicate some effects on postnatal survival, but these effects were seen at doses higher than maternal toxic dose levels. There are no clinical signs of cholinergic toxicity below 70% inhibition of brain cholinesterase. Cognitive or behavioral defects are not observed until substantial brain cholinesterase inhibition occurs. There are no indications that chlorpyrifos caused delayed neurotoxicity at dose levels below twice the oral LD50. The panel members stated that plasma cholinesterase was an inappropriate endpoint for the RfD. They recommended that brain, erythrocyte cholinesterase depression and clinical signs were appropriate as endpoints for the RfD. Plasma cholinesterase should be used only as an indicator of exposure. After a thorough review of the experimental animal literature, it was determined that the chlorpyrifos repeated-exposure RfD based on application of a 100-fold uncertainty factor on the no observed adverse effects level (NOAEL) for brain cholinesterase inhibition or on a 10-fold uncertainty factor on the NOAEL for erythrocyte cholinesterase inhibition is 0.01 mg/kg/d. Based on the human volunteer studies, which indicate a repeated-dose NOAEL of 0.1 mg/kg/d for erythrocyte cholinesterase inhibition, and then using a 10-fold uncertainty factor, the RfD is again 0.01 mg/kg/d. In this human volunteer study on d 9 (last day) of administration, 1 individual in the 0.1 mg/kg/day dose group was removed from the study due to a "cold" (runny nose, blurred vision, and a feeling of faintness). He was asymptomatic 12 h later. To some degree this diagnosis is supported by the hematology, since lymphocyte counts were reduced and neutrophil counts were increased markedly, indicating a possible inflammatory reaction on d 8 of dosing, clearing by posttreatment d 5. In the absence of any indication of erythrocyte cholinesterase inhibition and with plasma cholinesterase inhibition being greater in two of the four other individuals treated at the same dose level, these signs and symptoms are unlikely to have been induced by cholinesterase inhibition. The panel concluded that the symptoms this individual displayed were not an appropriate endpoint for the RfD. The single-exposure reference dose can be based on the human data. No erythrocyte cholinesterase inhibition or clinical signs of toxicity were observed after a single oral dose of 0.5 mg/kg. Utilizing a 10-fold uncertainty factor, the single-dose RfD is 0.05 mg/kg. Title: Expert panel report of human studies on chlorpyrifos and/or other organophosphate exposures Clegg DJ, van Gemert M Ref: J Toxicol Environ Health B Crit Rev, 2:257, 1999 : PubMed ESTHER: Clegg_1999_J.Toxicol.Environ.Health.B.Crit.Rev_2_257 PubMedSearch: Clegg 1999 J.Toxicol.Environ.Health.B.Crit.Rev 2 257 PubMedID: 10429681 Inhibitor(s) related to this paper: Chlorpyrifos Abstract A panel of toxicology and medical experts was convened on 7-9 April 1997 to consider the available scientific literature on chlorpyrifos, both published and unpublished, to determine the acute and chronic toxicology reference dose (RfD). In the course of reviewing this literature it became apparent that there was a large body of literature on human exposures to chlorpyrifos, as well as chlorpyrifos and/or other organophosphates. This literature, although not useful for determining the RfD for chlorpyrifos, needed to be analyzed for potential critical human effects resulting from either acute or prolonged chlorpyrifos exposures, or inferred from exposures to other organophosphates. The expert panel proceeded to review these data also, and the evaluations and discussions of these studies are contained in this report of the proceedings. The expert panel concluded that for acute poisonings there was no clear evidence for long-term effects from organophosphates, other than finding cases of organophosphorus-induced delayed neurotoxicity (OPIDN) from suicidal ingestion. In animal experimental data (mainly from studies on nerve gases), seizures during acute poisoning by organophosphates occur, resulting in morphological damage. Neurobehavioral effects observed are the result of the seizures. The panel agreed that long-term exposure to organophosphate compounds does not cause problems in the peripheral or central nervous system, unless poisoning is acute and severe. With respect to neurobehavioral effects, manifestations of clinical neurobehavioral effects are unlikely. All of the available evidence shows that disturbances do not occur unless cholinesterase inhibition has been clearly exhibited. The review of these papers was considered to be of interest in allaying some of the potential concerns regarding long-term effects of organophosphate pesticides, including chlorpyrifos. Title: Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides Gomes J, Dawodu AH, Lloyd O, Revitt DM, Anilal SV Ref: Hum Exp Toxicol, 18:33, 1999 : PubMed ESTHER: Gomes_1999_Hum.Exp.Toxicol_18_33 PubMedSearch: Gomes 1999 Hum.Exp.Toxicol 18 33 PubMedID: 10025366 Inhibitor(s) related to this paper: Triazophos, Chlorpyrifos, Dimethoate, Pirimiphos-methyl, Profenofos Abstract Chronic occupational exposure to organophosphorus and carbamate-type pesticides significantly inhibits acetylcholinesterase activity and causes morbidity. This study on mice was designed to evaluate their amino profile and to identify signs of hepatic dysfunction following their chronic exposure to mixtures of organophosphorus pesticides. Laboratory mice were exposed to a formulated mixture of the six organophosphorus pesticides (Dimethoate, Chlorpyrifos, Profenofos, Pirimiphos methyl, Triazophos and Dimethoate) most commonly used in agriculture in this region of the Middle East. Doses (10% of LD50 of the mixture) were given once a week by gavage in corn oil for 7 weeks; the control group was given only corn oil. At the end of the exposure period, mice were culled and blood samples were collected to determine erythrocyte acetylcholinesterase activity, biochemical markers of liver function and concentrations of serum amino acids. Erythrocyte acetylcholinesterase activity and total serum proteins decreased significantly in the exposed group. Serum concentrations of alanine aminotransferase and aspartate aminotransferase, alanine, glutamic acid, glycine, isoleucine, leucine, methionine, ornithine, proline, serine, threonine and valine were significantly increased in the exposed mice, while serum levels of cystine were decreased significantly. There were also non-significant increases in serum alkaline phosphatase, gama-glutamyl transpeptidase and some of the other amino acids. Chronic exposure to mixtures of organophosphorus pesticides is associated with decreased acetylcholinesterase activity, hepatic dysfunction and disturbance of amino acids profile. Biochemical indices of hepatocellular injury and disturbed amino acid metabolism may be of value as markers of chronic exposure to such pesticides. Title: Organophosphorus pesticide-induced butyrylcholinesterase inhibition and potentiation of succinylcholine toxicity in mice Sparks SE, Quistad GB, Casida JE Ref: J Biochem Mol Toxicol, 13:113, 1999 : PubMed ESTHER: Sparks_1999_J.Biochem.Mol.Toxicol_13_113 PubMedSearch: Sparks 1999 J.Biochem.Mol.Toxicol 13 113 PubMedID: 9890196 Inhibitor(s) related to this paper: Chlorpyrifos, Ethephon, Methamidophos, Phenyl-saligenin-phosphate~PSP, Profenofos, Tribufos Abstract Succinylcholine is the most important rapid-acting depolarizing muscle relaxant during anesthesia. Its desirable short duration of action is controlled by butyrylcholinesterase, the detoxifying enzyme. There are two reported cases of prolonged paralysis from succinylcholine in patients poisoned with the organophosphorus insecticides parathion and chlorpyrifos. The present study examines the possibility that other organophosphorus and methylcarbamate pesticides might also prolong succinylcholine action by inhibiting butyrylcholinesterase using mice treated intraperitoneally as a model and relating inhibition of blood serum hydrolysis of butyrylthiocholine to potentiated toxicity (mouse mortality). The organophosphorus plant defoliant tribufos (4 h pretreatment, 160 mg/kg) and organophosphorus plant growth regulator ethephon (1 h pretreatment, 200 mg/kg) potentiate the toxicity of succinylcholine by seven- and fourfold, respectively. Some other pesticides or analogs are more potent sensitizers for succinylcholine toxicity with threshold levels of 0.5, 1.0, 1.7, 8, 10, and 67 mg/kg for phenyl saligenin cyclic phosphonate, profenofos, methamidophos, tribufos, chlorpyrifos, and ethephon, respectively. Enhanced mortality from succinylcholine is generally observed when serum butyrylcholinesterase is inhibited 55-94%. Mivacurium, a related nondepolarizing muscle relaxant also detoxified by butyrylcholinesterase, is likewise potentiated by at least threefold on 4 hour pretreatment with tribufos (25 mg/kg) or profenofos (10 mg/kg). Title: Resistance to organophosphorus and pyrethroid insecticides in Culex pipiens (Diptera: Culicidae) from Tunisia Ben Cheikh H, Ben Ali-Haouas Z, Marquine M, Pasteur N Ref: Journal of Medical Entomology, 35:251, 1998 : PubMed ESTHER: Ben Cheikh_1998_J.Med.Entomol_35_251 PubMedSearch: Ben Cheikh 1998 J.Med.Entomol 35 251 PubMedID: 9615543 Inhibitor(s) related to this paper: Chlorpyrifos, Propoxur, Temephos Abstract Resistance to the organophosphates temephos and chlorpyrifos, the carbamate propoxur, the pyrethroid permethrin, and the organochloride DDT was investigated in Tunisian populations of Culex pipiens pipiens (L.) collected between 1990 and 1996. Resistance to temephos was uniformly low, reaching 10-fold in the most resistant population. In contrast, resistance to chlorpyrifos was highly variable, reaching the highest level (> 10,000-fold) recorded worldwide. The chlorpyrifos-resistant populations also were highly resistant to propoxur. Some populations also showed high resistance to permethrin (up to 5,000-fold) and moderate resistance to DDT (approximately 20-fold). Bioassays conducted in the presence of synergists showed that increased detoxification had only a minor role in resistance, although several over-produced esterases known to be involved in organophosphate resistance were detected. To better understand the factors influencing the distribution of resistance in Tunisia, the polymorphism of genes involved in organophosphate resistance (i.e., over-produced esterases and insensitive acetylcholinesterase) was investigated in relation to the genetic structure of populations studied by analyzing the electrophoretic polymorphism of "neutral" genes. Over the area studied, and despite a high level of gene flow, resistance genes showed a patchy distribution. Results are discussed in relation to the selection pressure caused by insecticide treatments. Title: Role of beta-naphthoflavone in the acute toxicity of chlorpyrifos in channel catfish Dalvi RR, Davis SW Ref: Bulletin of Environmental Contamination & Toxicology, 60:335, 1998 : PubMed ESTHER: Dalvi_1998_Bull.Environ.Contam.Toxicol_60_335 PubMedSearch: Dalvi 1998 Bull.Environ.Contam.Toxicol 60 335 PubMedID: 9470999 Inhibitor(s) related to this paper: Chlorpyrifos Title: Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration Dam K, Seidler FJ, Slotkin TA Ref: Brain Research Developmental Brain Research, 108:39, 1998 : PubMed ESTHER: Dam_1998_Brain.Res.Dev.Brain.Res_108_39 PubMedSearch: Dam 1998 Brain.Res.Dev.Brain.Res 108 39 PubMedID: 9693782 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Despite the fact that they recover more rapidly from cholinesterase inhibition than do adults, developing animals are more sensitive to delayed neurotoxicity caused by chlorpyrifos exposure. Previous studies indicate that acute, high dose chlorpyrifos exposure of developing rats interferes with synthesis of brain macromolecules, dependent upon a critical maturational stage and upon regional disparities in cholinergic innervation. In order to determine whether chronic, lower level chlorpyrifos exposure targets similar developmental events, rats were treated daily on postnatal days 1-4, using a dose (1 mg/kg, s.c.) that caused no mortality or weight deficits and that produces minimal cholinesterase inhibition. At the end of the treatment period, we examined macromolecule synthesis in three brain regions possessing disparate maturational profiles and cholinergic innervation: the brainstem, which undergoes its primary phase of neurogenesis prenatally and develops prominent cholinergic innervation, the forebrain, which develops somewhat later but also becomes cholinergically enriched, and the cerebellum, which undergoes neurogenesis postnatally and remains poor in cholinergic innervation. Four h after the last chlorpyrifos treatment, no effects were seen for DNA, RNA or protein synthesis. However, on postnatal day 5 (24 h after the last treatment), robust deficits in DNA synthesis were observed in brainstem and forebrain, with lesser effects on the cerebellum. Although the brain regional selectivity is compatible either with differences in critical maturational phases or with targeting of cholinergically-enriched brain regions, we found no significant effects in the heart, despite the fact that it is also receives cholinergic innervation. Effects on DNA synthesis were not evident 4 h after the last dose, but then appeared after 24 h. As the 4-h point is 28 h after the third dose, this suggests that a cumulative threshold needs to be exceeded in order for the delayed neurotoxicity to appear. At the point at which DNA synthesis was inhibited in brainstem and forebrain, no effects were seen for RNA or protein synthesis, indicating selectivity for macromolecule synthesis associated with cell replication. These data indicate that otherwise subtoxic, chronic exposures to chlorpyrifos nevertheless target DNA synthesis, and by inference, cell replication, in selective brain cell populations, early events that are likely contributors to the deficits in cell number that appear several days later. Title: The organophosphate pesticide chlorpyrifos affects form deprivation myopia Geller AM, Abdel-Rahman AA, Peiffer RL, Abou-Donia MB, Boyes WK Ref: Invest Ophthalmol Vis Sci, 39:1290, 1998 : PubMed ESTHER: Geller_1998_Invest.Ophthalmol.Vis.Sci_39_1290 PubMedSearch: Geller 1998 Invest.Ophthalmol.Vis.Sci 39 1290 PubMedID: 9620094 Inhibitor(s) related to this paper: Chlorpyrifos Abstract PURPOSE: The effects of the anti-cholinesterase organophosphate pesticide chlorpyrifos (CPF) on the refractive development of the eye were examined. Form deprivation was used to induce eye growth to address the previously reported relationship between organophosphate pesticide use and the incidence of myopia. METHODS: Chickens, a well-established animal model for experimental myopia and organophosphate neurotoxicity, were dosed with chlorpyrifos (3 mg/kg per day, orally, from day 2 to day 9 after hatching) or corn oil vehicle (VEH) with or without monocular form deprivation (MFD) over the same period. The set of dependent measures included the refractive state of each eye measured using retinoscopy, axial dimensions determined with A-scan ultrasound, and intraocular pressure. RESULTS: Dosing with CPF yielded an inhibition of 35% butyrylcholinesterase in plasma and 45% acetylcholinesterase in brain. MFD resulted in a significant degree of myopia in form-deprived eyes resulting from significant lengthening of the vitreal chamber of the eye. CPF significantly reduced the effect of MFD, resulting in less myopic eyes (mean refraction: VEH-MFD = -16.2 +/- 2.3 diopters; CPF-MFD = -11.1 +/- 1.8 diopters) with significantly shorter vitreal chambers. Nonoccluded eyes were, on average, slightly hyperopic. Treatment with CPF for 1 week in the absence of MFD led to no significant change in ocular dimensions or refraction relative to controls. CONCLUSIONS: The use of form deprivation as a challenge suggests that CPF treatment interferes with the visual regulation of eye growth Title: Human Exposure and Risk From Indoor Use of Chlorpyrifos Gibson JE, Peterson RKD, Shurdut BA Ref: Environmental Health Perspectives, 106:303, 1998 : PubMed ESTHER: Gibson_1998_Environ.Health.Perspect_106_303 PubMedSearch: Gibson 1998 Environ.Health.Perspect 106 303 PubMedID: 9618344 Inhibitor(s) related to this paper: Chlorpyrifos Abstract The toxicity, exposure, and risk from chlorpyrifos are briefly discussed in juxtaposition with two recent articles in Environmental Health Perspectives concerning potential exposures to children. In studies conducted according to EPA guidelines, chlorpyrifos has been shown not to be mutagenic, carcinogenic, or teratogenic, nor does it adversely affect reproduction. Chlorpyrifos toxicity does not occur in the absence of significant cholinesterase inhibition. If exposures are less than those that cause significant cholinesterase depression, then no signs or symptoms related to chlorpyrifos exposure occur. The weight of empirical evidence indicates that the risk of adults or children experiencing an adverse health effect from exposure to chlorpyrifos through both nondietary and dietary sources is negligible. Both the research supporting the registration of these products and their long history of widespread use suggest that unless these products are seriously misused, their margins of safety are wide enough to protect everyone with the potential to be exposed. A weight-of-evidence review of the entire scientific knowledge base relating to chlorpyrifos products supports these conclusions. Title: The dietary intake of chemical residues in Brisbane adults Harvey PW, Marks GC, Heywood PF Ref: Aust N Z J Public Health, 22:266, 1998 : PubMed ESTHER: Harvey_1998_Aust.N.Z.J.Public.Health_22_266 PubMedSearch: Harvey 1998 Aust.N.Z.J.Public.Health 22 266 PubMedID: 9744190 Inhibitor(s) related to this paper: Chlorpyrifos, Fenitrothion Abstract The purpose of this work was to integrate existing chemical residue and food consumption data for individuals to improve estimates of the dietary intake of chemical residues in the population of Brisbane. Previous estimates of intakes from the Australian Market Basket Survey (AMBS) have been based on energy-adjusted 'hypothetical national diets' and so allow no assessment of variation in intakes between individuals or groups. Data on concentration of fenitrothion, chlorpyrifos-methyl, pirimiphos-methyl, heptachlor and dieldrin in selected foods were taken from reports of the AMBS. Food consumption data were based upon the National Dietary Survey of Adults (NDSA) 1983; the same data from which the hypothetical diets are derived. The distribution of estimated 24-hour intakes was adjusted to represent usual intakes. Mean intakes of all residues were about one third those reported previously. None of the observed diets contained levels of residues that were greater than the Acceptable Daily Intakes. These findings support reassurances to the public that residues of agricultural chemicals monitored in the AMBS do not pose a health risk. Title: Early biochemical detection of delayed neurotoxicity resulting from developmental exposure to chloropyrifos Johnson DE, Seidler FJ, Slotkin TA Ref: Brain Research Bulletin, 45:143, 1998 : PubMed ESTHER: Johnson_1998_Brain.Res.Bull_45_143 PubMedSearch: Johnson 1998 Brain.Res.Bull 45 143 PubMedID: 9443830 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Developing animals are more sensitive than adults to the delayed neurotoxicity caused by chlorpyrifos exposure. In developing rat brain, chlorpyrifos doses that cause no discernible systemic toxicity and only a minor degree of cholinesterase inhibition, nevertheless evoke alterations in cell function and number that appear after several days' delay. In the current study, neonatal rats were exposed to subtoxic doses of chlorpyrifos (no weight loss or mortality) on either postnatal days 1-4, or postnatal days 11-14, and the effects on cellular RNA levels were determined in two brain regions that are targeted for delayed neurotoxicity-the brainstem and forebrain. In both regions, chlorpyrifos exposure evoked significant alterations in RNA concentration and content, variables that are ordinarily very tightly controlled in the developing brain. The effects on RNA appeared well before the deficits in cell function and number and showed a regional selectivity similar to that of subsequent, delayed neurotoxicity. Deficits in RNA were more prominent in the brainstem, an early-developing brain region, than in the forebrain, which develops later. These results suggest that chlorpyrifos can elicit delayed developmental neurotoxicity by targeting the pivotal macromolecules that control cell differentiation in a critical postmitotic period. The lower threshold for these cellular effects compared to that for systemic toxicity indicates that the developing brain is a selective target for chlorpyrifos, effects that should be considered in assessing safety thresholds. Title: Comparative presynaptic neurochemical changes in rat striatum following exposure to chlorpyrifos or parathion Liu J, Pope CN Ref: J Toxicol Environ Health, 53:531, 1998 : PubMed ESTHER: Liu_1998_J.Toxicol.Environ.Health_53_531 PubMedSearch: Liu 1998 J.Toxicol.Environ.Health 53 531 PubMedID: 9561967 Inhibitor(s) related to this paper: Chlorpyrifos, Parathion Abstract Organophosphorus pesticides (OPs) exert acute toxicity through inhibition of acetylcholinesterase (AChE) in target tissues. Previous studies in our laboratory have demonstrated, however, that dosages of the OPs chlorpyrifos (CPF) or parathion (PS), which cause similar degrees of brain AChE inhibition in adult male rats, can produce marked differences in toxicity. While compensatory changes in postsynaptic receptors can modulate the clinical expression of AChE inhibition and lead to tolerance to these toxicants, we propose that OP-selective changes in presynaptic cholinergic processes can also regulate the ultimate consequences of AChE inhibition. The relative effects of either vehicle (peanut oil, 2 ml/kg, sc), CPF (280 mg/kg), or PS (6.6 mg/kg) on clinical signs of toxicity and AChE activity, high-affinity choline uptake (HACU), and potassium-evoked acetylcholine (ACh) release in striatum were examined for a 7-d period after exposure in adult female Sprague-Dawley rats. In vitro effects of CPF-oxon or paraoxon, the active oxidative metabolites of CPF and PS, on HACU were also examined in comparison with the prototype inhibitor hemicholinium-3 (HC-3). Similar to our previous findings in male rats, female rats treated with dosages of CPF or PS causing similar maximal degrees of AChE inhibition (82-96%) exhibited marked differences in response; that is, PS produced more extensive signs of acute toxicity (salivation, lacrimation, urination and/or defecation, i.e., SLUD signs and involuntary movements). CPF reduced striatal synaptosomal HACU at 1, 2, and 7 d after exposure, whereas PS only decreased HACU at 2 d posttreatment. While CPF-oxon was a weak inhibitor of HACU (IC50 > 200 microM), paraoxon had no effect on this process in vitro. Potassium-evoked ACh release in the presence of physostigmine (20 microM) was not affected by either OP at 1 d but was increased 2 d after either CPF or PS treatment and remained elevated at 7 d after exposure in CPF-treated rats only. ACh release in the presence of both physostigmine and the muscarinic antagonist atropine (1 microM) was decreased by both OPs as early as 1 d after exposure and remained lower at 2 d posttreatment. By 7 d, however, ACh release in response to atropine was decreased in CPF-treated animals only, suggesting that both CPF and PS affected muscarinic autoreceptor function but with somewhat different time courses. These results suggest that different OPs may selectively modify presynaptic cholinergic processes and that early, OP-selective changes in HACU/ACh synthesis may contribute to the differential toxicity noted following extensive AChE inhibition by either CPF or PS. Title: Comparative Toxicity of Chlordane, Chlorpyrifos, and Aldicarb to Four Aquatic Testing Organisms Moore MT, Huggett DB, Gillespie WB, Jr., Rodgers JH, Jr., Cooper CM Ref: Archives of Environmental Contamination & Toxicology, 34:152, 1998 : PubMed ESTHER: Moore_1998_Arch.Environ.Contam.Toxicol_34_152 PubMedSearch: Moore 1998 Arch.Environ.Contam.Toxicol 34 152 PubMedID: 9469857 Inhibitor(s) related to this paper: Aldicarb, Chlorpyrifos Abstract Laboratory toxicity data contrasting responses of aquatic organisms to insecticides are important for focusing on sensitive species (steepest exposure-response slope) exposed to aqueous concentrations of these insecticides in field studies. These data also allow prediction of expected responses of aquatic species to a range of insecticide concentrations in situ. Aqueous 48-h toxicity tests were performed to contrast responses of Daphnia magna Straus, Hyalella azteca Saussure, Chironomus tentans Fabricius, and Pimephales promelas Rafinesque to acetylcholinesterase-inhibiting insecticides: chlorpyrifos, aldicarb, and chlordane. As expected, invertebrates tested (H. azteca, C. tentans, and D. magna) were >/= 200 times more sensitive than the vertebrate P. promelas to chlorpyrifos exposures. H. azteca was approximately 3.5 times more sensitive to chlorpyrifos (453% mortality/&mgr;g/L) than D. magna (128% mortality/&mgr;g/L). For both aldicarb and chlordane, C. tentans was the most sensitive species tested (2.44 and 2.54% mortality/&mgr;g/L, respectively). Differences in chlordane potency for test species varied only by a factor of approximately 2-3 (0.88% mortality/&mgr;g/L for H. azteca to 2.54% mortality/&mgr;g/L for C. tentans). Although point estimates of population responses such as LC50s, NOECs, and LOECs are of some utility for predicting effects of pesticides in aquatic systems, exposure-response slopes are also useful for extrapolation of laboratory data to diverse field situations, especially where sediment sorption may regulate insecticide exposure or bioavailability. Title: Comparison of the in vitro sensitivity of rat acetylcholinesterase to chlorpyrifos-oxon: what do tissue IC50 values represent? Mortensen SR, Brimijoin S, Hooper MJ, Padilla S Ref: Toxicol Appl Pharmacol, 148:46, 1998 : PubMed ESTHER: Mortensen_1998_Toxicol.Appl.Pharmacol_148_46 PubMedSearch: Mortensen 1998 Toxicol.Appl.Pharmacol 148 46 PubMedID: 9465262 Inhibitor(s) related to this paper: Chlorpyrifos Abstract The toxicological literature is replete with studies which have attempted to correlate differences in in vivo sensitivity to anticholinesterases with a common in vitro measure: acetylcholinesterase (AChE) IC50 values. Generally, it is assumed that these IC50 values reflect the intrinsic sensitivity of the AChE molecule to the inhibitor. Our goal was to ascertain whether differences in AChe sensitivity to an organophosphate (i.e., IC50 values) are due to varying properties of the enzyme molecule (i.e., present assumption) or to extrinsic factors. Tissue samples were obtained from immature and adult Long-Evans rats. AChE IC50 values were determined by incubating tissue homogenates with chlorpyrifos-oxon (active metabolite of chlorpyrifos, a common organophosphate insecticide) for 30 min at 26 degrees C, and then measuring residual AChE activity. The following IC50 values were noted for postnatal day 4 and adult animals, respectively: brain, 10 nM for both ages; liver, 96 and 527 nM; plasma, 18 and 326 nm. Thus, the "apparent" sensitivity of AChe was prone to vary dramatically with age and tissue type. In contrast, when AChE was isolated from the same tissues by immunoprecipitation, there were no age- or tissue- related differences (IC50 approximately equal to 3 nM in every case). These data show clearly that IC50 values from a crude homogenate do not measure the true sensitivity of AChE to the inhibitor. Presumably, for chlorpyrifos-oxon, at least, the tissue IC50 values depend greatly on a tissue's propensity to sequester or hydrolyze chlorpyrifos-oxon. Title: Age- and gender-related differences in the time course of behavioral and biochemical effects produced by oral chlorpyrifos in rats Moser VC, Padilla S Ref: Toxicol Appl Pharmacol, 149:107, 1998 : PubMed ESTHER: Moser_1998_Toxicol.Appl.Pharmacol_149_107 PubMedSearch: Moser 1998 Toxicol.Appl.Pharmacol 149 107 PubMedID: 9512733 Inhibitor(s) related to this paper: Chlorpyrifos Abstract It is well known that young animals are generally more sensitive to lethal effects of cholinesterase-inhibiting pesticides, but there are sparse data comparing less-than-lethal effects. We compared the behavioral and biochemical toxicity of chlorpyrifos in young (postnatal Day 17; PND17) and adult (about 70 days old) rats. First, we established that the magnitude of the age-related differences decreased as the rat matures. Next, we evaluated the time course of a single oral dose of chlorpyrifos in adult and PND17 male and female rats. Behavioral changes were assessed using a functional observational battery (with age-appropriate modifications for pre-weanling rats) and an evaluation of motor activity. Cholinesterase (ChE) activity was measured in brain and peripheral tissues and muscarinic receptor binding assays were conducted on selected tissues. Rats received either vehicle (corn oil) or chlorpyrifos (adult dose: 80 mg/kg; PND17 dose: 15 mg/kg); these doses were equally effective in inhibiting ChE. The rats were tested, and tissues were then taken at 1, 2, 3.5, 6.5, 24, 72, 168, or 336 h after dosing. In adult rats, peak behavioral changes and ChE inhibition occurred in males at 3.5 h after dosing, while in females the onset of functional changes was sooner, the time course was more protracted and recovery was slower. In PND17 rats, maximal behavioral effects and ChE inhibition occurred at 6.5 h after dosing, and there were no gender-related differences. Behavioral changes showed partial to full recovery at 24 to 72 h, whereas ChE inhibition recovered markedly slower. Blood and brain ChE activity in young rats had nearly recovered by 1 week after dosing, whereas brain ChE in adults had not recovered at 2 weeks. Muscarinic-receptor binding assays revealed apparent down-regulation in some brain areas, mostly at 24 and 72 h. PND17 rats generally showed more receptor down-regulation than adults, whereas only adult female rats showed receptor changes in striatal tissue that persisted for 2 weeks. Thus, compared to adults (1) PND17 rats show similar behavioral changes and ChE inhibition although at a five-fold lower dose; (2) the onset of maximal effects is somewhat delayed in the young rats; (3) ChE activity tended to recover more quickly in the young rats; (4) young rats appear to have more extensive muscarinic receptor down-regulation, and (5) young rats show no gender-related differences. Title: Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG and Lusis AJ <1 more author(s)> Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ (- 1) Ref: Nature, 394:284, 1998 : PubMed ESTHER: Shih_1998_Nature_394_284 PubMedSearch: Shih 1998 Nature 394 284 PubMedID: 9685159 Inhibitor(s) related to this paper: Chlorpyrifos, Parathion Abstract Serum paraoxonase (PON1) is an esterase that is associated with high-density lipoproteins (HDLs) in the plasma; it is involved in the detoxification of organophosphate insecticides such as parathion and chlorpyrifos. PON1 may also confer protection against coronary artery disease by destroying pro-inflammatory oxidized lipids present in oxidized low-density lipoproteins (LDLs). To study the role of PON1 in vivo, we created PON1-knockout mice by gene targeting. Compared with their wild-type littermates, PON1-deficient mice were extremely sensitive to the toxic effects of chlorpyrifos oxon, the activated form of chlorpyrifos, and were more sensitive to chlorpyrifos itself. HDLs isolated from PON1-deficient mice were unable to prevent LDL oxidation in a co-cultured cell model of the artery wall, and both HDLs and LDLs isolated from PON1-knockout mice were more susceptible to oxidation by co-cultured cells than the lipoproteins from wild-type littermates. When fed on a high-fat, high-cholesterol diet, PON1-null mice were more susceptible to atherosclerosis than their wild-type littermates. Title: Modeling the developmental neurotoxicity of chlorpyrifos in vitro: macromolecule synthesis in PC12 cells Song X, Violin JD, Seidler FJ, Slotkin TA Ref: Toxicol Appl Pharmacol, 151:182, 1998 : PubMed ESTHER: Song_1998_Toxicol.Appl.Pharmacol_151_182 PubMedSearch: Song 1998 Toxicol.Appl.Pharmacol 151 182 PubMedID: 9705902 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Exposure to apparently subtoxic doses of chlorpyrifos during late stages of brain development affects cell acquisition through a mixture of cholinergic and noncholinergic mechanisms. In the current study, we modeled these effects in vitro using rat pheochromocytoma (PC12), a cell line that, upon nerve-growth factor (NGF)-induced differentiation, develops the appearance and function of cholinergic target neurons, including the expression of cholinergic receptors. In the undifferentiated state (no NGF), chlorpyrifos evoked an immediate (1 h), robust, concentration-dependent inhibition of DNA synthesis as evaluated by [3H]thymidine incorporation, with a threshold of 0.5-1.5 microg/ml. Continuous exposure for up to 24 h maintained the same degree of inhibition. The effects were selective for DNA synthesis, as much smaller inhibitions were found for synthesis of RNA or protein. In contrast, direct cholinergic stimulation of the cells by 100 microM nicotine had much smaller effects on DNA synthesis. Moreover, the effects of chlorpyrifos on DNA synthesis could not be blocked by nicotinic or muscarinic antagonists, confirming that the effects were not mediated primarily through cholinergic hyperstimulation consequent to cholinesterase inhibition or to direct receptor-mediated effects. When PC12 cells underwent NGF-induced differentiation, the rate of cell replication fell dramatically and neurite extension was evident both from morphological examination and from biochemical markers (increased protein:DNA ratio). After introduction of NGF, chlorpyrifos maintained its ability to inhibit DNA synthesis acutely. However, the ability to inhibit RNA and protein synthesis initially intensified and then disappeared, indicating a shift in macromolecular targets as differentiation proceeded. We also tested the effects of long-term exposure to chlorpyrifos during the process of NGF-induced differentiation. Continuous chlorpyrifos exposure resulted in severe reductions in macromolecule synthesis and a deficit in the total number of cells, effects similar to those seen with chlorpyrifos treatment in vivo. At the highest concentrations, neurite extension was also inhibited. Our results suggest that chlorpyrifos can interact directly with developing neural cells to inhibit replication and neuritic outgrowth. Title: Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450- mediated metabolism Atterberry TT, Burnett WT, Chambers JE Ref: Toxicol Appl Pharmacol, 147:411, 1997 : PubMed ESTHER: Atterberry_1997_Toxicol.Appl.Pharmacol_147_411 PubMedSearch: Atterberry 1997 Toxicol.Appl.Pharmacol 147 411 PubMedID: 9439736 Inhibitor(s) related to this paper: Chlorpyrifos, Parathion Abstract Juvenile rats are more susceptible to the acute toxicity of the phosphorothionate insecticides parathion and chlorpyrifos than are adult rats. Developmental changes in brain acetylcholinesterase and hepatic aliesterase (carboxylesterase), cytochrome P450, and the P450-mediated metabolism of these two phosphorothionate insecticides were investigated in male Sprague-Dawley rats. Specific activities of acetylcholinesterase in cerebral cortex, but not medulla oblongata, and of liver aliesterases increased with age, indicating the presence of both more target esterases and more protective esterases, respectively, in the adult compared to the juvenile animal. Sensitivity of the brain acetylcholinesterase to inhibition by paraoxon and chlorpyrifosoxon, as measured by IC50 values, did not change significantly with age, whereas the hepatic aliesterase sensitivity to inhibition decreased with age. Progressive increases in activities of P450-mediated activation (desulfuration) (6- to 14-fold) and detoxication (dearylation) (2- to 4-fold), as well as concentrations of P450 (7-fold) and protein (2-fold), were observed between neonate and adult hepatic microsomes. Microsomal pentoxyresorufin O-dealkylase activity followed a developmental pattern similar to desulfuration and dearylation, displaying a 16-fold increase between neonates and adults. However, microsomal ethoxyresorufin O-deethylase activity increased until 21 days of age, displaying a 16-fold increase, then decreased in adulthood to a level 10-fold higher than neonates. These results indicate that target enzyme sensitivity is not responsible for age-related toxicity differences, nor is the potential for hepatic bioactivation, whereas lower levels of hepatic aliesterase-mediated protection and P450-mediated dearylation probably contribute significantly to the greater sensitivity of juveniles to phosphorothionate toxicity. Title: Distribution of organophosphate and carbamate resistance in Culex pipiens quinquefasciatus (Diptera: Culicidae) in West Africa Chandre F, Darriet F, Doannio JM, Riviere F, Pasteur N, Guillet P Ref: Journal of Medical Entomology, 34:664, 1997 : PubMed ESTHER: Chandre_1997_J.Med.Entomol_34_664 PubMedSearch: Chandre 1997 J.Med.Entomol 34 664 PubMedID: 9439121 Inhibitor(s) related to this paper: Carbosulfan, Chlorpyrifos, Propoxur, Temephos Abstract The distribution of organophosphate and carbamate resistance was investigated in 33 samples of Culex pipiens quinquefasciatus Say from 25 cities in Cte d'Ivoire and Burkina Faso. Organophosphate resistance levels were higher in Cte d'Ivoire than in Burkina Faso. Chlorpyrifos resistance ratios at LC95 ranged from 4 to 30 times in Cte d'Ivoire and from 3 to 6 times in Burkina Faso. For temephos, ratios ranged from 3 to 18 and from 1 to 2, respectively. Of 27 samples from Cte d'Ivoire, 25 also displayed cross resistance to carbamates as shown by a mortality plateau in bioassays with propoxur and carbosulfan (similar to chlorpyrifos). Cross resistance to organophosphates and carbamates was caused by an insensitive acetylcholinesterase allele (AceR). This gene was absent from Burkina Faso, except in Niangoloko near the Cte d'Ivoire border. Organophosphate resistance also was associated with the presence of A2-B2 overproduced esterases which had higher frequencies in Cte d'Ivoire (75-100%) than in Burkina Faso (40-50%). Two other esterases with the same electrophoretic mobility as C2 from Puerto Rico and B1 from California were identified for the 1st time in West Africa. "C2" was widespread, whereas "B1" was present in only a few mosquitoes from Cte d'Ivoire. These differences in resistance patterns should be taken into consideration in planning urban mosquito control strategies within 2 countries. Title: Hypothermia and delayed fever in the male and female rat exposed to chlorpyrifos Gordon CJ, Grantham TA, Yang Y Ref: Toxicology, 118:149, 1997 : PubMed ESTHER: Gordon_1997_Toxicology_118_149 PubMedSearch: Gordon 1997 Toxicology 118 149 PubMedID: 9129169 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Chlorpyrifos (CHL) is a commonly used organophosphate (OP) pesticide which irreversibly inhibits acetylcholinesterase activity in the CNS. Little is known regarding the thermoregulatory effects of CHL when administered orally and whether the sensitivity to CHL is affected by sex. To address these issues, male and female rats of the Long-Evans strain were administered 0, 10, 50, or 80 mg/kg CHL by gavage while core temperature (T(c)) and motor activity (MA) were monitored continuously by telemetry. Females were generally more sensitive than males to CHL. Significant hypothermic responses to CHL were observed in males administered 80 mg/kg and in females administered 10-80 mg/kg. Following recovery from hypothermia T(c) of both males and females underwent a significant elevation during the light phase 1-2 days after CHL exposure. CHL-induced hyperthermia was blocked in male and female rats by administration of 200 mg/kg sodium salicylate (SS), an antipyretic agent. Male castrated rats were markedly more sensitive to the hypothermic and hyperthermic effects of CHL compared to sham operated controls. On the other hand, ovariectomized female rats responded to CHL in a similar fashion as the sham operated controls. Thus, testicular function may be important in determining greater resistance to CHL in male rats. It appears that exposure to CHL leads to a delayed fever which involves activation of CNS pathways normally involved in fever. This mechanism could be responsible for the febrile response to OP pesticides commonly observed in humans exposed to OPs. Title: Oxidative liver DNA damage in rats treated with pesticide mixtures Lodovici M, Casalini C, Briani C, Dolara P Ref: Toxicology, 117:55, 1997 : PubMed ESTHER: Lodovici_1997_Toxicology_117_55 PubMedSearch: Lodovici 1997 Toxicology 117 55 PubMedID: 9020199 Inhibitor(s) related to this paper: Benomyl, Chlorfenvinphos, Chlorpyrifos, Methylparathion, Parathion, Pirimiphos-methyl Abstract Oxidative damage was quantified in the liver of rats by measuring the levels of 8-OH-2-deoxyguanosine (8-OH-2DG) relative to 2-deoxyguanosine in DNA after treating rats for 10 days at a total dose of 1 mg/kg/day with a mixture of the 15 pesticides most commonly found in Italian foods (comprised of dithiocarbamate, benomyl, procymidone, methidathion, chlorpyrifos-ethyl, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos ethyl, thiabendazole, fenarimol, diphenylamine and chlorothalonil). We fractionated this pesticide mixture into subgroups in order to determine which molecules, if any, induced DNA oxidative damage. The administration of diphenylamine (0.09-1.4 mg/kg/day) and chlorothalonil (0.13-1 mg/kg/day) induced a dose-dependent increase in 8-OH-2DG levels in liver DNA. The other 13 pesticides of the mixture on the contrary, did not produce oxidative liver DNA damage. These results indicate that the toxicity of low doses of pesticide mixtures present in food might be further reduced by eliminating diphenylamine and chlorothalonil. Title: [Determination of insecticide resistance and its biochemical mechanisms in 2 strains of Culex quinquefasciatus from Santiago de Cuba] Rodriguez MM, Bisset J, Rodriguez I, Diaz C Ref: Rev Cubana Med Trop, 49:209, 1997 : PubMed ESTHER: Rodriguez_1997_Rev.Cubana.Med.Trop_49_209 PubMedSearch: Rodriguez 1997 Rev.Cubana.Med.Trop 49 209 PubMedID: 9685989 Inhibitor(s) related to this paper: Chlorpyrifos, Malathion, Propoxur Abstract It was analyzed the behavior of the resistance of 3 organophosphated insecticides (malathion, clorpirifos and methyl-pyrimifos), 3 pyrethroids (deltamethrin, lambda-cyhalothrin and cypermethrin), and 1 carbamate (propuxur) in populations of Culex quinquefasciatus from 2 municipalities of the province of Santiago de Cuba. The values of the resistance factor proved that there is resistance to malathion and clorpirifos. However, in spite of the existence of a high frequency of the mechanisms of elevated esterases and altered acetylcholinesterase no resistance to methylpymirifos, was observed which demonstrated that this insecticide is not affected by these mechanisms selected in our populations of Culex quinquefasciatus. There was resistence to deltamethrin, and lambda-cyhalothrin in Santiago de Cuba, whereas it was moderate to cypermethrin in Santiago and San Luis. Resistance to deltamethrin was also found in San Luis, but it was mild to lambda-cyhalothrin. The results obtained from the use of the synergists S,S,S tributyl phosphotritiade (DBF) and piperonyl butoxide (PB) indicated that the mechanisms of resistance of unspecific esterases and oxidases of multiple function are involved in the resistance to pyrethroids in both strains from Santiago de Cuba and San Luis. It was determined by the biochemical tests that there existed a high frequency of the mechanisms of esterases and altered acetylcholinesterase. The results of the polyacrylamide gel electrophoresis (PAGE) showed that esterase B1 appears more frequently associated with esterases A6 and B6. It was inferred that this association could be connected with the resistance to pyrethroids. Title: Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade Song X, Seidler FJ, Saleh JL, Zhang J, Padilla S, Slotkin TA Ref: Toxicol Appl Pharmacol, 145:158, 1997 : PubMed ESTHER: Song_1997_Toxicol.Appl.Pharmacol_145_158 PubMedSearch: Song 1997 Toxicol.Appl.Pharmacol 145 158 PubMedID: 9221834 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Developmental neurotoxicity caused by chlorpyrifos exposure is generally thought to target cholinesterase but chlorpyrifos may also act on cellular intermediates, such as adenylyl cyclase, that serve global functions in the coordination of cell development. In the current study, neonatal rats were exposed to apparently subtoxic doses of chlorpyrifos (no weight loss, no mortality) either on Postnatal Days 1-4 or on Postnatal Days 11-14, and the effects on components of the adenylyl cyclase cascade were evaluated in brain regions that are enriched (forebrain) or sparse (cerebellum) in cholinergic innervation, as well as in a nonneural tissue (heart). In all three, chlorpyrifos evoked deficits in multiple components of the adenylyl cyclase cascade: expression and activity of adenylyl cyclase itself, functioning of G-proteins that link neurotransmitter and hormone receptors to cyclase activity, and expression of neurotransmitter receptors that act through this cascade. Disruption of signaling function was not restricted to transduction of cholinergic signals but rather extended to adrenergic signals as well. In most cases, the adverse effects were not evident during the immediate period of chlorpyrifos administration, but appeared after a delay of several days. These results suggest that chlorpyrifos can affect cell development by altering the activity and reactivity of the adenylyl cyclase signaling cascade, a major control point for trophic regulation of cell differentiation. The effects are not restricted to cholinergic targets, nor even to the central nervous system. Hence, disruption of cell development by chlorpyrifos is likely to be more widespread than previously thought. Title: Evaluation of organophosphorus pesticide residues in citrus fruits from the Valencian community (Spain) Torres CM, Pico Y, Marin R, Manes J Ref: Journal of AOAC International, 80:1122, 1997 : PubMed ESTHER: Torres_1997_J.AOAC.Int_80_1122 PubMedSearch: Torres 1997 J.AOAC.Int 80 1122 PubMedID: 9325585 Inhibitor(s) related to this paper: Carbophenothion, Chlorfenvinphos, Chlorpyrifos, Diazinon, Ethion, Fenitrothion, Malathion, Methidathion, Methylparathion, Phosmet, Quinalphos Abstract Approximately 200 citrus samples from markets of the Valencian Community (Spain) were analyzed to establish their residue levels in 12 organophosphorus pesticide residues during the 1994-1995 campaign. The organophosphorus pesticides carbophenothion, chlorpyriphos, chlorfenvinphos, diazinon, ethion, fenitrothion, malathion, methidation, methylparathion, phosmet, quinalphos, and tetradifon were simultaneously extracted by matrix solid-phase dispersion and determined by gas chromatography-mass spectrometry using selected ion monitoring mode. A total of 32.25% contained pesticide residues and 6.9% exceeded the European Union Maximum Residue Levels (MRLs). The pesticides found in the samples with residues above MRLs were carbophenothion, ethion, methidathion, and methyl parathion. Lower level residues of these and the other pesticides studied (except diazinon) were frequently found. The estimated daily intake of the 12 organophosphorus pesticide residues during the studied period was 4.87 x 10(-4) mg/kg body weight/day. This value is lower than the provisional tolerances dairy intakes proposed by the Food and Agriculture Organization and the World Health Organization. Title: Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning Worek F, Backer M, Thiermann H, Szinicz L, Mast U, Klimmek R, Eyer P Ref: Hum Exp Toxicol, 16:466, 1997 : PubMed ESTHER: Worek_1997_Hum.Exp.Toxicol_16_466 PubMedSearch: Worek 1997 Hum.Exp.Toxicol 16 466 PubMedID: 9292287 Inhibitor(s) related to this paper: Chlorfenvinphos, Chlorpyrifos, Diazinon, Parathion Abstract 1 In vitro studies with human erythrocyte acetylcholinesterase (AChE) and the mouse diaphragm model were performed to unravel the various microscopic reaction parameters that contribute to the dynamic equilibrium of AChE inhibition, ageing and reactivation. These data may help to define more precisely the indications and limitations of oxime therapy in organophosphate (OP) poisoning. 2 Diethylphosphoryl-AChE resulting from intoxications with parathion, chlorpyrifos, chlorfenvinphos, diazinon and other OPs is characterized by slow spontaneous reactivation and low propensity for ageing. This kind of phosphorylated enzyme is particularly susceptible to reactivation by oximes. 3 None of the oximes tested (pralidoxime, obidoxime, HI 6 and HLo 7) can be regarded as a universally suitable reactivator. Obidoxime turned out to be the most potent and most efficacious oxime in reactivating AChE inhibited by various classes of OP insecticides and tabun. Obidoxime, however, was inferior to HI 6 against soman, sarin, cyclosarin and VX. Pralidoxime was generally less potent. 4 The kinetic data of reactivation established for diethylphosphoryl-AChE of human red cells indicate that the usually recommended dosage to attain a plasma concentration of 4 micrograms/ml does not permit exploitation of the full therapeutic potential of the oximes, in particular of pralidoxime. However, in suicidal mega-dose poisoning, oximes, even at optimal plasma concentrations, may be unable to cope with the fast re-inhibition of reactivated AChE in the first days following intoxication. 5 It is suggested that oximes be administered by continuous infusion following an initial bolus dose as long as reactivation can be expected and until permanent clinical improvement is achieved. Title: Time course of inhibition of cholinesterase and aliesterase activities, and nonprotein sulfhydryl levels following exposure to organophosphorus insecticides in mosquitofish (Gambusia affinis) Boone JS, Chambers JE Ref: Fundamental & Applied Toxicology, 29:202, 1996 : PubMed ESTHER: Boone_1996_Fundam.Appl.Toxicol_29_202 PubMedSearch: Boone 1996 Fundam.Appl.Toxicol 29 202 PubMedID: 8742317 Inhibitor(s) related to this paper: Chlorpyrifos, Methylparathion, Parathion Abstract Cholinesterase (ChE) in brain and muscle was quickly inhibited during a 48-hr in vivo exposure to chlorpyrifos (0.1 ppm), parathion (0.15 ppm), and methyl parathion (8 ppm) in mosquitofish (Gambusia affinis). ChE remained inhibited during a 96-hr nonexposure period. Brain ChE reached peak inhibition by 12 hr after exposure to parathion and chlorpyrifos and by 4 hr after exposure to methyl parathion. All insecticides caused greater than 70% ChE inhibition by 4 hr in muscle. There was no recovery of ChE after 4 days of nonexposure in either brain or muscle. Hepatic aliesterases (AliE) were quickly and greatly inhibited (> 70% by 4 hr) after exposure to parathion and chlorpyrifos but not after exposure to methyl parathion. Exposure to methyl parathion required 24-36 hr to inhibit hepatic AliE to the same level as that following parathion and chlorpyrifos exposures at 4 hr. Exposure to all insecticides eventually resulted in greater than 80% inhibition of AliE. None of the test groups treated with insecticides showed any signs of significant recovery of AliE during the 4 days of nonexposure. Nonprotein sulfhydryl (NPSH) concentrations were lower than controls after 24 hr of exposure and 96 hr after recovery for all compounds. Exposure to methyl parathion lowered NPSH concentrations greater than the other compounds. Hepatic AliE appear capable of affording some protection of ChE from inhibition following parathion or chlorpyrifos exposures, but considerably less protection against methyl parathion. Title: Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon Carr RL, Chambers JE Ref: Toxicology & Applied Pharmacology, 139:365, 1996 : PubMed ESTHER: Carr_1996_Toxicol.Appl.Pharmacol_139_365 PubMedSearch: Carr 1996 Toxicol.Appl.Pharmacol 139 365 PubMedID: 8806854 Inhibitor(s) related to this paper: Chlorpyrifos, Chlorpyrifos-oxon, Paraoxon, Parathion Abstract In rats, the phosphorothionate insecticide parathion exhibits greater toxicity than chlorpyrifos, while in catfish the toxicities are reversed. The in vitro inhibition of brain acetylcholinesterase (AChE) by the active metabolites of the insecticides and the rates at which these inhibitor-enzyme complexes undergo reactivation/ aging were investigated in both species. Rat AChE was more sensitive to inhibition than catfish AChE as demonstrated by greater bimolecular rate constants (ki) in rats than in catfish. In both species, chlorpyrifos-oxon yielded higher ki's than paraoxon. The higher association constant (KA) of chlorpyrifos-oxon than paraoxon in both species and the lack of significant differences in the phosphorylation constants (kp) suggest that association of the inhibitor with AChE is the principal factor in the different potencies between these two inhibitors. In catfish, the ki of chlorpyrifos-oxon was 22-fold greater than that of paraoxon, while in rats it was 9-fold greater, suggesting that target site sensitivity is an important factor in the higher toxicity of chlorpyrifos to catfish but not in the higher toxicity of parathion to rats. No spontaneous reactivation of phosphorylated catfish AChE occurred and there were no differences in the first oder aging constants (ka) between compounds. For phosphorylated rat AChE, there were no differences in the first order reactivation constants (kr) but the ka for chlorpyrifos-oxon was significantly greater than that for paraoxon. This difference suggests that the steric positioning of the diethyl phosphate in the esteratic site is not the same between the two compounds, leading to differences in aging. Title: Selective, solid-matrix dispersion extraction of organophosphate pesticide residues from milk Di Muccio A, Pelosi P, Camoni I, Attard Barbini D, Dommarco R, Generali T, Ausili A Ref: Journal of Chromatography A, 754:497, 1996 : PubMed ESTHER: Di Muccio_1996_J.Chromatogr.A_754_497 PubMedSearch: Di Muccio 1996 J.Chromatogr.A 754 497 PubMedID: 8997741 Inhibitor(s) related to this paper: Triazophos, Azinphos-Methyl, Chlorfenvinphos, Chlorpyrifos, Diazinon, Ethion, Fenitrothion, Phenthoate, Fonofos, Heptenophos, Isofenphos, Malathion, Methidathion, Methylparathion, Mocap, Omethoate, Phosalone, Pirimiphos-methyl, Pyrazophos, Quinalphos Abstract A rapid procedure has been developed that allows a single-step, selective extraction and cleanup of organophosphate (OP) pesticide residues from milk dispersed on solid-matrix diatomaceous material filled into disposable cartridges by means of light petroleum saturated with acetonitrile and ethanol. Recovery experiments were carried out on homogenized commercial milk (3.6% fat content) spiked with ethanolic solutions of 24 OP pesticides, viz., ethoprophos, diazinon, dimethoate, chlorpyrifos-methyl, parathion-methyl, chlorpyrifos-ethyl, malathion, isofenphos, quinalphos, ethion, pyrazophos, azinphosethyl, heptenophos, omethoate, fonofos, pirimiphos-methyl, fenitrothion, parathion, chlorfenvinphos, phenthoate, methidathion, triazophos, phosalone, azinphos-methyl, at levels ranging for the different OP pesticides from 0.02 mg/kg to 1.11 mg/kg. Average recoveries of four replicates were in the range 72-109% for the different OP pesticides, with relative standard deviations (R.S.D.) from ca. 1 to 19%, while dimethoate and omethoate were not recovered. Coextracted fatty material amounted to an average of about 4.0 mg/ml of milk. The extraction procedure requires about 30 min. The main advantages are that extraction and cleanup are carried out in a single step, emulsions do not occur, several samples can be run in parallel by a single operator, reusable glassware is not needed and simple operations are required. Title: Organohalogen and organophosphorus pesticides in mixed feed rations: findings from FDA's domestic surveillance during fiscal years 1989-1994 Lovell RA, McChesney DG, Price WD Ref: Journal of AOAC International, 79:544, 1996 : PubMed ESTHER: Lovell_1996_J.AOAC.Int_79_544 PubMedSearch: Lovell 1996 J.AOAC.Int 79 544 PubMedID: 8920144 Inhibitor(s) related to this paper: Chlorpyrifos, Diazinon, Malathion, Methylchlorpyrifos, Pirimiphos-methyl Abstract 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. Title: Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae Sanchez-Fortun S, Sanz F, Barahona MV Ref: Archives of Environmental Contamination & Toxicology, 31:391, 1996 : PubMed ESTHER: Sanchez-Fortun_1996_Arch.Environ.Contam.Toxicol_31_391 PubMedSearch: Sanchez-Fortun 1996 Arch.Environ.Contam.Toxicol 31 391 PubMedID: 8854833 Inhibitor(s) related to this paper: Chlorpyrifos, Hexamethonium, Methylchlorpyrifos, Methylparathion, Parathion Abstract 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). Title: Matrix solid-phase dispersion extraction procedure for multiresidue pesticide analysis in oranges Torres CM, Pico Y, Redondo MJ, Manes J Ref: Journal of Chromatography A, 719:95, 1996 : PubMed ESTHER: Torres_1996_J.Chromatogr.A_719_95 PubMedSearch: Torres 1996 J.Chromatogr.A 719 95 PubMedID: 8589838 Inhibitor(s) related to this paper: Azinphos-Methyl, Carbophenothion, Chlorfenvinphos, Chlorpyrifos, Diazinon, Ethion, Fenitrothion, Malathion, Methidathion, Methylparathion, Phosmet Abstract A multiresidue extraction method based on matrix solid-phase dispersion (MSPD) is optimized for the extraction and gas chromatographic screening of eighteen insecticides (aldrin, carbophenothion, captafol, chlorpyriphos, chlorfenvinphos, diazinon, dicofol, alpha-endosulfan, beta-endosulfan, ethion, fenitrothion, folpet, methidathion, malathion, methyl-azinphos, methyl-parathion, phosmet, and tetradifon) from oranges. After optimization of different parameters, such as type of solid phase used and the amount of solid phase or eluent, recoveries ranged from 67 to 102% with relative standard deviations ranging from 2 to 10%. The limits of detection, calculated as 3 times the baseline noise ranged from 2 to 171 micrograms/kg. These limits of detection were about 10 times lower than the maximum residue levels established by the European Community. Compared with classical methods, the described procedure is simple, less labour intensive and does not require preparation and maintenance of equipment. Troublesome emulsions, such as those frequently observed in liquid-liquid partitioning did not occur. Title: Organophosphate resistance in Culex pipiens from Cyprus Wirth MC, Georghiou GP Ref: J Am Mosq Control Assoc, 12:112, 1996 : PubMed ESTHER: Wirth_1996_J.Am.Mosq.Control.Assoc_12_112 PubMedSearch: Wirth 1996 J.Am.Mosq.Control.Assoc 12 112 PubMedID: 8723267 Inhibitor(s) related to this paper: Chlorpyrifos, Dichlorvos, Fenthion, Malathion, Pirimiphos-methyl, Propoxur Abstract Populations of Culex pipiens were sampled from 8 locations in Cyprus between 1987 and 1993. All population samples generally revealed organophosphate resistance to malathion, temephos, chlorpyrifos, fenthion, dichlorvos, and pirimiphos methyl, in decreasing order of magnitude. Of 7 populations assessed with the carbamate propoxur, all proved to be resistant to different degrees. Of the 6 populations tested with permethrin, 2 were resistant to permethrin. Resistance was associated with the presence of 5 different overproduced esterases (esterases A1, A2, A5, B2, and B5) as well as an insensitive form of acetylcholinesterase. These results are discussed in relation to the ongoing mosquito abatement program in Cyprus and to similar programs in other parts of the world. Title: Effects of three organophosphorus insecticides in the reproductive potential of Culex quinquefasciatus Aguilera L, Marquetti MC, Navarro A, Bisset J Ref: Mem Inst Oswaldo Cruz, 90:411, 1995 : PubMed ESTHER: Aguilera_1995_Mem.Inst.Oswaldo.Cruz_90_411 PubMedSearch: Aguilera 1995 Mem.Inst.Oswaldo.Cruz 90 411 PubMedID: 8544743 Inhibitor(s) related to this paper: Chlorpyrifos, Malathion, Pirimiphos-methyl Abstract A Culex quinquefasciatus Say 1823 strain with resistant genes to organophosphates was tested in the laboratory to know the reproductive potential after exposure, as larvae, at the LC30 and LC70 (mg/l) of three organophosphorus insecticides: malathion, chlorpyrifos and methyl-pirimiphos. Data showed that fecundity was decreased significantly by malathion at LC30 = 0.0025 and LC70 = 0.0075, whereas fertility has a no significant decrement by chlorpyrifos and methyl-pirimiphos at the LC70 (0.000016, 0.00043). The sexual index was affected by chlorpyrifos and methyl-pirimiphos showing a greater number of adult females. Title: Inhibition and aging of channel catfish brain acetylcholinesterase following exposure to two phosphorothionate insecticides and their active metabolites Carr RL, Straus DL, Chambers JE Ref: Journal of Toxicology & Environmental Health, 45:325, 1995 : PubMed ESTHER: Carr_1995_J.Toxicol.Env.Health_45_325 PubMedSearch: Carr 1995 J.Toxicol.Env.Health 45 325 PubMedID: 7541841 Inhibitor(s) related to this paper: Chlorpyrifos, Chlorpyrifos-oxon, Paraoxon, Parathion Abstract The inhibition and aging of acetylcholinesterase (AChE) in fingerling channel catfish (lctalurus punctatus) brain tissue was studied after single in vivo exposures to high levels of chlorpyrifos (0.25 mg/L), chlorpyrifos-oxon (7 micrograms/L), parathion (2.5 mg/L), or paraoxon (30 micrograms/L). Exposure to both parent compounds produced identical initial inhibition (95%), but in the later sampling times there was significantly more inhibited AChE in the chlorpyrifos-treated fish than in the parathion-treated fish (47% and 28%, respectively, on d 16). There were higher levels of aged AChE following chlorpyrifos exposure than following parathion exposure, but differences were not significant. Exposure to both oxons produced initial inhibition greater than 90%, and patterns of recovery and aging were statistically similar between both compounds; no significant inhibition was observed after d 11. The similar patterns of inhibition, recovery, and aging between the two oxon treatments, which have similar lipophilicities, suggest that the greater amount of AChE inhibition and aging observed in the chlorpyrifos-treated fish compared with the parathion-treated fish probably results from the higher lipophilicity of chlorpyrifos than of parathion. Overall, the prolonged brain AChE inhibition exhibited in catfish exposed to phosphorothionates is not the result of aging of the inhibited enzyme but is the result of either a slow rate or a lack of spontaneous reactivation. Title: Comparative developmental and maternal neurotoxicity following acute gestational exposure to chlorpyrifos in rats Chanda SM, Harp P, Liu J, Pope CN Ref: Journal of Toxicology & Environmental Health, 44:189, 1995 : PubMed ESTHER: Chanda_1995_J.Toxicol.Env.Health_44_189 PubMedSearch: Chanda 1995 J.Toxicol.Env.Health 44 189 PubMedID: 7531776 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Chlorpyrifos (CPF), an organophosphorus (OP) insecticide, exerts toxicity through inhibition of acetylcholinesterase (AChE). In the present study, pregnant Sprague-Dawley rats were given CPF (200 mg/kg, sc) as a single dose on gestation d 12 (GD12) and then sacrificed on either GD16, GD20, or postnatal d 3 (PND3) for measurement of maternal and developmental indicators of toxicity. While most CPF-treated rats exhibited no overt signs, a subset (4/28) showed moderate to severe signs of "cholinergic" toxicity at 2-3 d after treatment, and these rats were omitted from further studies. Extensive AChE inhibition (82-88%) was noted in maternal brain at all three time points following acute exposures. At GD16 and GD20, fetal brain AChE activity was inhibited 42-44%. While some degree of recovery in AChE activity was noted in pup brain by PND3, AChE activity was still inhibited (30%) in treated pups cross-fostered to control dams. In vitro inhibition of maternal and fetal (GD20) brain AChE activity by the active metabolite, chlorpyrifos oxon, suggested that the prenatal brain AChE activity was somewhat more sensitive (IC50 at 37.0 degrees C, 20 min: dam, 26.6 +/- 1.8 x 10(-9) M; fetus, 6.7 +/- 0.4 x 10(-9) M). Maternal brain muscarinic receptor binding was more extensively reduced (30-32%) at GD20 and PND3 as compared to the developing brain at GD20 (16%) and PND3 (11%). A simple postnatal reflex test (righting reflex) was transiently altered by CPF. The results suggest that CPF exposure to dams during gestation produces more extensive neurotoxicological effects in the dam relative to the developing fetus. Title: Slow accumulation of acetylcholinesterase in rat brain during enzyme inhibition by repeated dosing with chlorpyrifos Chiappa S, Padilla S, Koenigsberger C, Moser V, Brimijoin S Ref: Biochemical Pharmacology, 49:955, 1995 : PubMed ESTHER: Chiappa_1995_Biochem.Pharmacol_49_955 PubMedSearch: Chiappa 1995 Biochem.Pharmacol 49 955 PubMedID: 7537966 Inhibitor(s) related to this paper: Chlorpyrifos Abstract When given to rats, O,O'-diethyl-O-[3,5,6-trichloro-2-pyridyl]- phosphorothionate (chlorpyrifos), a common insecticide, causes an unusually lengthy dose-dependent fall in the activity of brain acetylcholinesterase (AChE; EC 3.1.1.7). To determine whether the slow recovery involves impaired AChE synthesis, experiments were designed to measure AChE activity, immunoreactive AChE protein (AChE-IR) and AChE mRNA. Male, Long-Evans rats, maintained at 350 +/- 5 g, were dosed (s.c.) weekly for 4 weeks with 0, 15, 30, or 60 mg/kg chlorpyrifos in peanut oil. Brain tissue was harvested 1, 3, 5, 7 and 9 weeks after treatment began. AChE activity was measured by Ellman assay, and AChE-IR was estimated by two-site ELISA using monoclonal antibodies to rat brain AChE. While AChE activity fell significantly at all times and doses, AChE-IR increased at 3 and 5 weeks in the two higher dosage groups. Larger increases of AChE-IR were observed after chlorpyrifos was administered for 4 weeks by the oral route. Northern blots quantified with reference to cyclophilin were consistent with stable levels of AChE mRNA. Overall, it appears that chronically reduced brain AChE activity after chlorpyrifos reflects sustained enzyme inhibition, not loss of enzyme protein or suppression of AChE message. Title: Characterization of resistance to organophosphate, carbamate, and pyrethroid insecticides in field populations of Aedes aegypti from Venezuela Mazzarri MB, Georghiou GP Ref: J Am Mosq Control Assoc, 11:315, 1995 : PubMed ESTHER: Mazzarri_1995_J.Am.Mosq.Control.Assoc_11_315 PubMedSearch: Mazzarri 1995 J.Am.Mosq.Control.Assoc 11 315 PubMedID: 8551300 Inhibitor(s) related to this paper: Chlorpyrifos, Pirimiphos-methyl, Propoxur Abstract Resistance to the organophosphates (OP) temephos, malathion, and pirimiphos methyl, and the carbamate propoxur was found to be low (< 5-fold) in 3 Aedes aegypti populations collected from Falcon and Aragua states of Venezuela. Resistance to chlorpyrifos (OP), permethrin, and lambda-cyhalothrin (pyrethroids) was moderate (7-fold) in both populations. Mechanisms of resistance were investigated with the synergists piperonyl butoxide (mixed function oxidase inhibitor) and S, S, S-tributyl phosphorothioate (DEF, an esterase inhibitor). Nonspecific esterase and oxidase enzymes played a significant role in OP and carbamate resistance, respectively. Resistance to pyrethroid insecticides was not affected by DEF or piperonyl butoxide. This suggested the presence of another mechanism such as altered target site sensitivity (kdr). Biochemical tests showed significantly greater amounts of esterase activity in field strains, whereas insensitive acetylcholinesterase was not involved in either OP or carbamate resistance. These results must be considered in future control programs for Ae. aegypti, because OPs and pyrethroids are currently used in vector control in most countries of Central and South America. Title: Resistance to organophosphorous insecticides in Culex pipiens quinquefasciatus (Diptera: Culicidae) from Martinique Yebakima A, Raymond M, Marquine M, Pasteur N Ref: Journal of Medical Entomology, 32:77, 1995 : PubMed ESTHER: Yebakima_1995_J.Med.Entomol_32_77 PubMedSearch: Yebakima 1995 J.Med.Entomol 32 77 PubMedID: 7541837 Inhibitor(s) related to this paper: Chlorpyrifos, Methylchlorpyrifos, Temephos Abstract 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. Title: Cytogenetic effects on human lymphocytes of a mixture of fifteen pesticides commonly used in Italy Dolara P, Torricelli F, Antonelli N Ref: Mutat Res, 325:47, 1994 : PubMed ESTHER: Dolara_1994_Mutat.Res_325_47 PubMedSearch: Dolara 1994 Mutat.Res 325 47 PubMedID: 7521012 Inhibitor(s) related to this paper: Chlorfenvinphos, Chlorpyrifos, Methidathion, Methylparathion, Parathion, Pirimiphos-methyl Abstract Lymphocytes obtained from 5 healthy donors were incubated with a mixture of 15 pesticides commonly found in foods of central Italy (dithiocarbamates (20.7%), benomyl (19.6%), thiabendazole (14.9%), diphenylamine (14.4%), chlorthalonil (13.1%), procymidone (8.0%), methidathion (2.3%), chlorpyrifos-ethyl (2%), fenarimol (1.9%), parathion-methyl (1%), chlorpropham, parathion, vinchlozolin, chlorfenvinphos and pirimiphos-ethyl (< 1%)). The percent of each pesticide in the mixture was proportional to its average concentration in foods. Incubated with the lymphocytes at a concentration of 1-20 micrograms/ml the pesticide mixture did not induce significant variations in the number of hypodiploid, hyperdiploid and polyploid cells or in the number of chromosome and chromatid aberrations. On the contrary, we observed a dose-dependent increase in the number of nonsynchronous centromeric separations which reached the level of 37.9% at 20 micrograms/ml of pesticide mixture in the incubation medium. This effect was not observed when benomyl was excluded from the mixture. These data show that the removal of benomyl could decrease the toxicity of pesticide residues present in human food. Title: Insecticide susceptibility in mosquitoes (Diptera: Culicidae) from French Polynesia Failloux AB, Ung A, Raymond M, Pasteur N Ref: Journal of Medical Entomology, 31:639, 1994 : PubMed ESTHER: Failloux_1994_J.Med.Entomol_31_639 PubMedSearch: Failloux 1994 J.Med.Entomol 31 639 PubMedID: 7966164 Inhibitor(s) related to this paper: Bromophos, Chlorpyrifos, Fenitrothion, Fenthion, Malathion, Permethrin, Temephos Abstract Susceptibility to six organophosphate (OP), two pyrethroid (PY), and one carbamate (C) insecticides was investigated in Culex pipiens quinquefasciatus Say, Aedes aegypti (L.), and Aedes polynesiensis Marks larvae from the island of Tahiti. Cx. p. quinquefasciatus and Ae. aegypti were compared with susceptible reference strains treated simultaneously. A low, but significant, resistance to bromophos (4.6x), chlorpyrifos (5.7x), fenthion (2.4x), fenitrothion (5.0x), temephos (4.3x) and permethrin (2.1x) was found in Cx. p. quinquefasciatus, and to malathion (1.5x), temephos (2.3x), permethrin (1.8x) and propoxur (1.7x) in Ae. aegypti. Cx. p. quinquefasciatus was shown to possess over-produced esterases A2 and B2, which are known to be involved in resistance to OPs in other countries. Ae. polynesiensis was less resistant than the Ae. aegypti reference strain to all insecticides except temephos (1.8x) and permethrin (6.7x). To determine whether Ae. polynesiensis had developed resistance to these insecticides in Tahiti, a geographical survey covering 12 islands of the Society, Tuamotu, Tubuai, Marquesas, and Gambier archipelagoes was undertaken with three insecticides (temephos, deltamethrin, and permethrin). Two- to threefold variations in LC50S were observed among collections. Results are discussed in relationship to the level of insecticide exposure on the different islands. Title: Genetic toxicity of a mixture of fifteen pesticides commonly found in the Italian diet Dolara P, Vezzani A, Caderni G, Coppi C, Torricelli F Ref: Cell Biol Toxicol, 9:333, 1993 : PubMed ESTHER: Dolara_1993_Cell.Biol.Toxicol_9_333 PubMedSearch: Dolara 1993 Cell.Biol.Toxicol 9 333 PubMedID: 8039010 Inhibitor(s) related to this paper: Chlorfenvinphos, Chlorpyrifos, Methidathion, Methylparathion, Parathion, Pirimiphos-methyl Abstract To determine the toxicological effects of complex mixtures of pesticides, we obtained data on 100 pesticide residues in common foods of central Italy. Fifteen pesticides were more regularly detected at higher levels (dithiocarbamates, benomyl/carbendazim, thiabendazole, diphenylamine, chlorthalonil, procymidone, fenarimol, chlorpropham, vinchlozolin, methidathion, chlorpyriphos-ethyl, parathion-methyl, parathion, chlorfenviphos, pirimiphos-ethyl). Using itemized data on daily food consumption in Italy, we calculated that the average exposure for an adult subject was 716 micrograms/day, ranging from 148 micrograms of dithiocarbamates to 1 microgram of pirimiphos-ethyl. We made a mixture of these 15 pesticides at concentrations proportional to the ratio determined in foods and tested it with the Salmonella-microsome assay, with and without metabolic activation with PCB-induced rat liver S9. No mutagenic activity was observed at concentrations up to 500 micrograms/plate. We also tested the same mixture at concentrations ranging from 0.1 to 20 micrograms/ml on human lymphocytes in vitro, and observed a slight but statistically significant increase in sister-chromatid exchanges at 1 microgram/ml. We also administered the mixture in corn oil by gavage to Wistar rats at doses of 1, 10, and 100 micrograms/kg. After 24 hr the ratio between bone marrow polychromatic and normochromatic lymphocytes (a sign of cellular toxicity) was decreased by the exposure, but we did not observe a significant increase in the frequency of micronuclei. We conclude that the pesticide mixture did not have appreciable genotoxic activity in the assays used. Title: Serum paraoxonase status: a major factor in determining resistance to organophosphates Li WF, Costa LG, Furlong CE Ref: Journal of Toxicology & Environmental Health, 40:337, 1993 : PubMed ESTHER: Li_1993_J.Toxicol.Env.Health_40_337 PubMedSearch: Li 1993 J.Toxicol.Env.Health 40 337 PubMedID: 7693961 Inhibitor(s) related to this paper: Chlorpyrifos, Chlorpyrifos-oxon, Paraoxon, Parathion Abstract A number of lines of evidence suggest that serum paraoxonase is protective against poisoning by organophosphorus substrates of this enzyme. Birds that have very low levels of paraoxon hydrolyzing activity in their sera are very susceptible to parathion poisoning. Rabbits, which have a sevenfold higher enzyme level compared with rats, have a fourfold higher resistance to paraoxon poisoning than rats. Rabbit paraoxonase hydrolyzes chlorpyrifos-oxon with a much higher turnover number than does rat paraoxonase, resulting in a very high resistance of rabbits to chlorpyrifos toxicity. Direct tests of paraoxonase protection have been carried out by injecting purified rabbit enzyme into rats. The protection achieved was higher for chlorpyrifos-oxon than for paraoxon, probably due to the high hydrolytic activity of the rabbit enzyme for chlorpyrifos-oxon. In humans, a substrate-dependent polymorphism of serum paraoxonase is observed, where one isoform of paraoxonase has a high turnover number for paraoxon and the other a low turnover number. Both isoforms appear to hydrolyze chlorpyrifos-oxon and phenylacetate at the same rate. Cloning and sequencing of the human paraoxonase cDNAs has elucidated the molecular basis of the polymorphism. Arginine at position 192 determines high paraoxonase activity, and glutamine at this position, low paraoxonase activity. In addition to the polymorphism, a 13-fold variation in serum enzyme levels within a given genetic class is seen. The experiments reported here demonstrate that rabbit paraoxonase injected into mice provides protection against the parent insecticide chlorpyrifos as well as the toxic oxon. These results suggest that serum paraoxonase status may serve as a biomarker for insecticide susceptibility in humans. Title: Urinary excretion of diethylphosphorus metabolites in persons poisoned by quinalphos or chlorpyrifos Vasilic Z, Drevenkar V, Rumenjak V, Stengl B, Frobe Z Ref: Archives of Environmental Contamination & Toxicology, 22:351, 1992 : PubMed ESTHER: Vasilic_1992_Arch.Environ.Contam.Toxicol_22_351 PubMedSearch: Vasilic 1992 Arch.Environ.Contam.Toxicol 22 351 PubMedID: 1375016 Inhibitor(s) related to this paper: Chlorpyrifos, Quinalphos Abstract The urinary excretion rates of diethyl phosphate and diethyl phosphorothioate and changes in blood cholinesterase activities were studied in fifteen persons self-poisoned either by the organophosphorus pesticide quinalphos (twelve persons) or by chlorpyrifos (three persons). The organophosphate poisoning was always indicated by a significant depression of serum and/or red blood cell cholinesterase activities. The return of serum cholinesterase activity in the range of referent values took more than 30 days and had a different course in different persons. The most rapid increase in red blood cell acetylcholinesterase activity was noted within 24 h after the first treatment with oximes Pralidoxime and/or HI-6. None of the spot urine samples, collected daily after admission of persons to hospital, contained measurable quantities of the parent pesticide. There was no correlation between the maximum concentration of total urinary diethylphosphorus metabolites normalized to creatinine and the initial inhibition of blood cholinesterase activities measured in samples collected on the day of admission to hospital. The excretion of metabolites followed the kinetics of a biphasic reaction. The half-time of urinary metabolites concentration decrease in the fast excretion phase in quinalphos poisoned persons was 5.5-14.2 h (eight persons) and 26.8-53.6 h (four persons) and in chlorpyrifos poisoned persons 3.5-5.5 h. The half-time for the slow excretion phase ranged from 66.5 to 127.9 h in all persons and for both compounds. For a given person, the rates of excretion of diethyl phosphate and diethyl phosphorothioate were about the same. However, in quinalphos poisoned persons the proportions of single metabolites in total diethylphosphorus metabolites varied with the initial maximum concentration of total metabolites. Title: Recent advances in cleanup of fats by sweep co-distillation. Part 2. Organophosphorus residues Luke BG, Richards JC Ref: J Assoc Off Analytical Chemistry, 67:902, 1984 : PubMed ESTHER: Luke_1984_J.Assoc.Off.Anal.Chem_67_902 PubMedSearch: Luke 1984 J.Assoc.Off.Anal.Chem 67 902 PubMedID: 6501152 Inhibitor(s) related to this paper: Bromophos, Chlorpyrifos, Ethion Abstract This paper describes the isolation of 5 organophosphorus residues in beef fat by a commercial sweep co-distillation unit (Unitrex). The operating conditions specified 223 degrees C and nitrogen flow at 230 mL/min. Recoveries of chlorpyriphos, monodechlorchlorpyriphos, bromophos-ethyl, debromobromophos-ethyl, and ethion ranged from 84 to 99%, with coefficients of variation between 3 and 5%. Title: [Effect of temephos on acetylcholinesterase activity in the brain of Tilapia guineensis. 3: Comparative effect of temephos and 3 substitute insecticides] Pellissier C, Leung Tack D, Gras G Ref: Toxicol Eur Res, 5:63, 1983 : PubMed ESTHER: Pellissier_1983_Toxicol.Eur.Res_5_63 PubMedSearch: Pellissier 1983 Toxicol.Eur.Res 5 63 PubMedID: 6193610 Inhibitor(s) related to this paper: Chlorphoxim, Chlorpyrifos, Pirimiphos-methyl, Temephos Abstract The Onchocerciasis Control Programme (OCP) is realized in the major part of the treated area by weekly applications of temephos in biotopes of simulles larvae. This insecticide is very effective and its impact on the aquatic fauna is evaluated by means of periodic samplings of the fauna. Therefore, the most sensitive way of tracking down fish poisoning is by studying the brain acetylcholinesterase depression. Evaluated on Tilapia guineensis this lowering is moderate when operational doses are used by OCP. The discovery of resistence to temephos incited researchers of OCP to try remplacement insecticides. Among these, chlorphoxim, chlorpyrifos-methyl and pirimiphos-methyl proved to be the most effect of these three organophosphorus compounds to that of temephos on the acetylcholinesterasic activity of the brain of Tilapia but using a much higher dosage (0,05 mg/l during 24 hrs that is 144 times more than for temephos). The results demonstrate that the three remplacement insecticides have on inhibitive effect plainly more important than that of temephos and that the retour to normal activity requires a much longer time. Title: Dislodgable insecticide residues on cotton foliage: fenvalarate, permethrin, sulprofos, chlorpyrifos, methyl parathion, EPN, oxamyl, and profenofos Buck NA, Estesen BJ, Ware GW Ref: Bulletin of Environmental Contamination & Toxicology, 24:283, 1980 : PubMed ESTHER: Buck_1980_Bull.Environ.Contam.Toxicol_24_283 PubMedSearch: Buck 1980 Bull.Environ.Contam.Toxicol 24 283 PubMedID: 6153915 Inhibitor(s) related to this paper: Chlorpyrifos, EPN, Isofenphos, Methylparathion, Oxamyl, Profenofos, Sulprofos Title: Residual toxicity of wall-sprayed organophosphates, carbamates and pyrethroids to mosquito Culex pipiens molestus Forskal Rettich F Ref: J Hyg Epidemiol Microbiol Immunol, 24:110, 1980 : PubMed ESTHER: Rettich_1980_J.Hyg.Epidemiol.Microbiol.Immunol_24_110 PubMedSearch: Rettich 1980 J.Hyg.Epidemiol.Microbiol.Immunol 24 110 PubMedID: 7190586 Inhibitor(s) related to this paper: Bendiocarb, Chlorpyrifos, Diazinon, Dioxacarb, Fenitrothion, Malathion, Pirimiphos-methyl, Promecarb, Propetamphos, Propoxur Abstract Common house mosquito Culex pipiens molestus Forskal was used to test biologically the residual toxicity of 15 organophosphorus, 5 carbamate and 5 pyrethroid insecticide preparations sprayed on whitewashed or limewashed wall surfaces. The doses of 0.1 g and 1.0 g of active ingredient per 1 m2 of wall surface were used in this experiment. At the dose of 1 g/m2, organophosphates chlorpyriphos, diazinon, fenitrothion, malathion, pirimiphos-methyl and propetamphos, cambamates bendiocarb, dioxacarb, propoxur and promecarb, and pyrothroids bioresmethrin, decamethrin-permethrin and tetramethrin produced on whitewashed wall surfaces the residual toxicity persisting for at least four months. At the dose of 0.1 g/m2, a long-lasting residual toxicity persisting on whitewashed wall surfaces for at least two months was observed after bendiocarb, decamethrin, fenitrothion, permethrin, pirimiphos-methyl and propoxur application. The residual toxicity of organophosphates, carbamates except for bendiocarb and pyrethroids except for permethrin sprayed on limewashed wall surfaces was considerably shorter than on whitewashed surface. Title: Isolation and concentration of organophosphorus pesticides from drinking water at the ng/L level, using macroreticular resin LeBel GL, Williams DT, Griffith G, Benoit FM Ref: J Assoc Off Analytical Chemistry, 62:241, 1979 : PubMed ESTHER: LeBel_1979_J.Assoc.Off.Anal.Chem_62_241 PubMedSearch: LeBel 1979 J.Assoc.Off.Anal.Chem 62 241 PubMedID: 447594 Inhibitor(s) related to this paper: Chlorpyrifos, Cruformate, Diazinon, Diazinon-oxon, Dimethoate, Ethion, Fenchlorphos, Fenitrothion, Isofenphos, Malathion, Methidathion, Parathion, Phosalone, Phosmet, Phosphamidon Abstract A screening method has been developed for determining organophosphorus pesticides at ng/L levels in drinking water. Sixteen organophosphorus pesticides, diazinon, diazinon-oxon, dimethoate, ronnel, beta-phosphamidon, methyl parathion, ethyl parathion, malathion, chlorpyrifos, fenitrothion, ruelene, methidathion, ethion, EPN, phosalone, and phosmet, were extracted by Amberlite XAD-2 resin from 100 and 200 L drinking water previously spiked with these pesticides. The pesticides were eluted from the XAD-2 resin with acetone-hexane (15+85). The concentrated extract was analyzed by gas chromatography using a nitrogen-phosphorus selective detector and by gas chromatography-mass spectrometry using selected ion monitoring. Recoveries at the 10 and 100 ng/L spiking levels were greater than 90%, except recoveries for dimethoate and phosphamidon were 37 and 42%, respectively. The analysis of 300 L Ottawa tap water showed no detectable amounts (less than 1 ng/L) of any of the 16 organophosphorus pesticides. Title: Trials with chlorpyrifos (Dursban) as a systemic insecticide against the cattle louse Loomis EC, Lobb PG, Webster AN Ref: Vet Rec, 98:168, 1976 : PubMed ESTHER: Loomis_1976_Vet.Rec_98_168 PubMedSearch: Loomis 1976 Vet.Rec 98 168 PubMedID: 56801 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Data for louse control are presented chiefly on chlorpyrifos (Dursban) 0, 0-diethyl 0-(3, 5, 6-trichloro-2-pyridyl) phosphorothioate and fenchlorphos in one trial and chlorpyrifos and famphur in three trials. These animal systemics were tested on 168 dairy calves in four herds located in three regions of the North Island, New Zealand. Louse control, following single backline, dermal applications, showed 80%, 87% and 100% with dosages of chlorpyrifos at 5 mg, 13 mg and 20 to 200 mg per kg, respectively, and 100% and 93% with dosages of famphur at 20 mg per kg, respectively. Poor louse control (24 to 58%) with fenchlorphos was expected since this compound requires two applications 14 days apart. Ovicidal effect was demonstrated with chlorpyrifos and famphur. Minor scurfing and hair loss occurred on some calves with all compounds, but hair coats were normal 28 days after treatment. Calves given 100 mg to 200 mg per kg chlorpyrifos showed signs of organophosphate toxicity from 5 mins to 90 mins post-treatment but were normal thereafter. Title: Detection of O,O-diethyl-O-(2,5-dichlorophenyl) phosphorothioate and O,O-diethyl-O-(3,6-dichloro-2-pyridyl) phosphorothioate in meat fat Luke BG, Dahl CJ Ref: J Assoc Off Analytical Chemistry, 59:1081, 1976 : PubMed ESTHER: Luke_1976_J.Assoc.Off.Anal.Chem_59_1081 PubMedSearch: Luke 1976 J.Assoc.Off.Anal.Chem 59 1081 PubMedID: 61199 Inhibitor(s) related to this paper: Chlorpyrifos, Ethyl-bromophos Abstract Two previously unreported organophosphorus residues have been detected in meat fat. The first, O,O-diethyl-O-(2,5-dichlorophenyl) phosphorothioate, apparently results from the debromination of bromophos-ethyl, while the other, O,O-diethy-O-(3,6-dichloro-2-pyridyl) phosphorothioate, presumably arises by the monodechlorination of chlorpyriphos. Mass spectral evidence is presented in support of the assigned structures and gas-liquid chromatographic retention data for the residues and their oxygen analogs are provided. | ||||||||
|
