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Mutagenesis Mar 2008There is considerable concern regarding the biological plausibility of the response of certain chemicals in the in vitro photoclastogenicity assay, suggesting that this... (Comparative Study)
Comparative Study
There is considerable concern regarding the biological plausibility of the response of certain chemicals in the in vitro photoclastogenicity assay, suggesting that this assay is oversensitive and lacks specificity. To explore this further, four coded compounds (aminotriazole, propantheline bromide, cycloheximide and disulfoton) were evaluated for their potential response in a photoclastogenicity assay in cultured Chinese hamster ovary (CHO) cells. None of the four compounds were shown to absorb ultraviolet radiation (UVR) or visible light in the 290- to 700-nm region of the electromagnetic spectrum. A fifth coded compound, tetracycline, which absorbs UVR, was also tested as this has previously been shown to be phototoxic in vitro (3T3-NRU assay) and is cytotoxic, but not genotoxic, at high concentrations in standard 'dark' genotoxicity assays in mammalian cells. The results showed that cycloheximide, disulfoton and tetracycline were clastogenic in CHO cells following UVR exposure (solar-simulated light at 700 mJ/cm(2)) but not in the absence of UVR. Aminotriazole and propantheline were negative in the presence and absence of UVR exposure. Follow-up testing showed that neither cycloheximide nor disulfoton was positive in the 3T3-NRU assay, the standard in vitro regulatory test for phototoxicity, a result consistent with their inability to absorb UVR. These data suggest that both cycloheximide and disulfoton are pseudophotoclastogens, like zinc oxide. Together, these data question the specificity of the in vitro photoclastogencity assay in CHO cells and raises further concern regarding its use for the assessment of chemical photosafety for regulatory purposes. At the very least, a review of the current guidance documents for the photosafety evaluation of pharmaceuticals and cosmetics should be undertaken urgently.
Topics: Amitrole; Animals; CHO Cells; Chromosome Aberrations; Cricetinae; Cricetulus; Cycloheximide; DNA Damage; Disulfoton; Mutagenicity Tests; Mutagens; Propantheline; Tetracycline; Ultraviolet Rays
PubMed: 18227081
DOI: 10.1093/mutage/gem053 -
Environmental Science and Pollution... Dec 2023Pesticide deposits post-treatment and before diffusing inside the plants are exposed to sunlight. Many of them degrade into a variety of photoproducts that may be...
Pesticide deposits post-treatment and before diffusing inside the plants are exposed to sunlight. Many of them degrade into a variety of photoproducts that may be harmful to living beings through accidental ingestion. The addition of ultraviolet light absorbers to the pesticide formulations is an attractive strategy to prevent photodegradation of the pesticides. Water-soluble quaternary ammonium ultraviolet light absorbers (QAUVAs) were synthesized from 2,4-dihydroxy benzophenones (BP-1) and their structures were confirmed by H NMR, C NMR, UV, and FTIR. A cost-saving approach for the photoprotection of disulfoton insecticide using these QAUVAs is presented. All the four QAUVAs exhibit excellent UV screening effect. The insecticide disulfoton was recovered in much higher amounts (22.27 ~ 25.64% higher than control) when it was irradiated in the presence of QAUVAs in comparison with the amount of recovery of pesticide exposed in absence of them.
Topics: Photolysis; Disulfoton; Insecticides; Ultraviolet Rays; Pesticides; Benzophenones
PubMed: 35687284
DOI: 10.1007/s11356-022-21247-1 -
Journal of Toxicology and Environmental... 1981The induction of anticholinesterase tolerance has, in the past, been achieved by using multiple doses of organophosphorus ester insecticides that initially caused...
The induction of anticholinesterase tolerance has, in the past, been achieved by using multiple doses of organophosphorus ester insecticides that initially caused cholinergic signs. The purpose of this study was to ascertain whether anticholinesterase tolerance could be induced with doses of an anticholinesterase that produced no overt cholinergic signs. Rats were fed diets containing 0, 7.5, or 20 ppm disulfoton. Animals fed at the 7.5 ppm level were without cholinergic signs throughout the period of feeding. Rats from this group were significantly more resistant to the lethal effect of carbachol than rats given the control diet after 58 and 62 d on the diet. Animals fed 20 ppm disulfoton in the diet initially showed signs that gradually disappeared with time on the diet. Rats fed at this level were more resistant to the lethal effect of carbachol than controls on all challenge dates (30, 45, 58, and 62 d on the diets) and more resistant than animals fed 7.5 ppm only on d 38 and 45. Thus the organophosphorus ester insecticide disulfoton, fed to rats in a dietary concentration that depressed acetylcholinesterase but was insufficient to cause cholinergic signs, induced tolerance to the lethal effects of carbachol. The length of time on an experimental diet before resistance to carbachol could be demonstrated was greater for the experimental group given 7.5 ppm disulfoton than the group given 20 ppm disulfoton in the diet.
Topics: Animals; Carbachol; Cholinesterase Inhibitors; Disulfoton; Drug Tolerance; Female; Insecticides; Rats; Time Factors
PubMed: 7328703
DOI: 10.1080/15287398109530063 -
Journal of Environmental Science and... 1979The residues of disulfoton and permethrin in an organic soil and in vegetables grown in soil treated with a granular formulation of the pesticides were determined by gas...
The residues of disulfoton and permethrin in an organic soil and in vegetables grown in soil treated with a granular formulation of the pesticides were determined by gas chromatography. The residues were removed from soil or plant samples by successive extractions with acetone and hexane. Permethrin persisted in the soil for the initial 28 days and declined slowly during the rest of the season but disulfoton after persisting for one week at the applied concentration was degraded in the next two weeks. The insecticides did not translocate into the edible parts of the vegetables but were present in the root system of onion and lettuce. Carrot and lettuce yields were not singificantly different from those of the controls but onion yields were substantially decreased by the use of permethrin.
Topics: Chromatography, Gas; Disulfoton; Insecticides; Methods; Pesticide Residues; Pyrethrins; Soil; Vegetables
PubMed: 438462
DOI: 10.1080/03601237909372123 -
Journal of Toxicology. Clinical... 1995A 75-year-old woman attempted suicide by ingesting a large quantity of granular Di-Syston which is an organophosphate insecticide containing 5% disulfoton...
A 75-year-old woman attempted suicide by ingesting a large quantity of granular Di-Syston which is an organophosphate insecticide containing 5% disulfoton (ethylthiometon). On admission, the total plasma phosphorodithioate sulfone concentration (disulfoton and its metabolites, phosphorodithioate sulfoxide and its sulfone) determined by gas chromatography was 1095 ng/mL. After gastric lavage, the concentration gradually decreased to 505 ng/mL. However, it began to increase again 20 h after admission and reached the peak concentration (1322 ng/mL) at 56 h. It was concluded that the secondary elevation of the plasma concentration was due to the prolonged absorption of the organophosphate from the residual granules in the stomach, despite the early gastric lavage. Pralidoxime iodide administration temporarily restored erythrocyte cholinesterase activity to almost normal and inhibited the excessive, delayed reduction of cholinesterase activity. It is recommended that poisoning with the granular form of disulfoton should be treated with repetitive or prolonged gastric and intestinal lavage, charcoal, and a continuous intravenous infusion of pralidoxime iodide in addition to atropine sulfate.
Topics: Aged; Cholinesterase Reactivators; Cholinesterases; Disulfoton; Erythrocytes; Female; Humans; Pralidoxime Compounds; Suicide, Attempted; Time Factors
PubMed: 7897754
DOI: 10.3109/15563659509000465 -
Biochemical Pharmacology Sep 2004Phorate and disulfoton are organophosphate insecticides containing three oxidizable sulfurs, including a thioether. Previous studies have shown that only the thioether...
Phorate and disulfoton are organophosphate insecticides containing three oxidizable sulfurs, including a thioether. Previous studies have shown that only the thioether is oxygenated by flavin-containing monooxygenase (FMO) and the sole product is the sulfoxide with no oxygenation to the sulfone. The major FMO in lung of most mammals, including non-human primates, is FMO2. The FMO2*2 allele, found in all Caucasians and Asians genotyped to date, codes for a truncated, non-functional, protein (FMO2.2A). Twenty-six percent of individuals of African descent and 5% of Hispanics have the FMO2*1 allele, coding for full-length, functional protein (FMO2.1). We have here demonstrated that the thioether-containing organophosphate insecticides, phorate and disulfoton, are substrates for expressed human FMO2.1 with Km of 57 and 32 microM, respectively. LC/MS confirmed the addition of oxygen and formation of a single polar metabolite for each chemical. MS/MS analysis confirmed the metabolites to be the respective sulfoxides. Co-incubations with glutathione did not reduce yield, suggesting they are not highly electrophilic. As the sulfoxide of phorate is a markedly less effective acetylcholinesterase inhibitor than the cytochrome P450 metabolites (oxon, oxon sulfoxide or oxon sulfone), humans possessing the FMO2*1 allele may be more resistant to organophosphate-mediated toxicity when pulmonary metabolism is an important route of exposure or disposition.
Topics: Animals; Disulfoton; Humans; Insecticides; Lung; Mice; Microsomes; Oxidation-Reduction; Oxygenases; Phorate; Rabbits
PubMed: 15294458
DOI: 10.1016/j.bcp.2004.05.051 -
Neurotoxicology Dec 1981Tolerance to the toxic effects of exposure to the organophosphate acetylcholinesterase inhibitor, disulfoton, was induced by giving multiple, sublethal doses of the...
Tolerance to the toxic effects of exposure to the organophosphate acetylcholinesterase inhibitor, disulfoton, was induced by giving multiple, sublethal doses of the compound to male rats. Tolerance was judged to have been induced when toxic signs of exposure, including weight loss, were reversed or diminished. Binding of the specific muscarinic radioligand, [3H] quinuclidinyl benzilate ([3H] QNB) to ileal muscle, forebrain, and hindbrain from treated animals was significantly less than the amount bound to tissue from the control animals. Binding of [3H] QNB to heart tissue from tolerant animals was not different from control values. After a typical tolerance-inducing regimen of 7 doses of 2 mg/kg/day disulfoton followed by 4 doses of 3 mg/kg/day, [3H] QNB binding to heart from treated animals was 104% of controls, while binding to ileal muscle, forebrain, and hindbrain was 67, 69, and 77% of control values (p less than .001, .001 and .01), respectively. [3H] QNB binding was not decreased due to competition for binding sites with excess acetylcholine. Neither were decreases due to displacement by disulfoton, as an acute dose of disulfoton (which caused marked inhibition of acetylcholinesterase) did not result in decreased binding. The maximal binding (Bmax) to forebrain of tolerant animals was 56% of control (1.06 vs 1.88 pmol [3H] QNB mg protein-1, p less than 0.01), but no statistically significant change could be seen in equilibrium dissociation constants (Kd, 0.35 vs 0.36 nM). No changes in [3H] QNB binding constants occurred in hearts form tolerant animals. Differences between tolerant and control groups could be seen in [3H] QNB binding to striatum, but no alterations occurred in this brain area in the binding of dopaminergic or gabaergic radiolabels. The data presented in consistent with the hypothesis that cholinergic receptors are involved in organophosphate tolerance.
Topics: Animals; Body Weight; Brain; Disulfoton; Drug Tolerance; Insecticides; Male; Myocardium; Quinuclidinyl Benzilate; Rats; Rats, Inbred Strains; Receptors, Cholinergic; Receptors, Muscarinic
PubMed: 7200580
DOI: No ID Found -
Psychopharmacologia 1971
Topics: Analysis of Variance; Animals; Chronic Disease; Exploratory Behavior; Female; Male; Mice; Phosphoric Acids; Sex Factors
PubMed: 5090536
DOI: 10.1007/BF00404370 -
Journal of Environmental Science and... May 1994Potatoes were grown during 1992 in 2 m2 plots of loam which had received 1, 2 or 3 annual treatments of Di-Syston 15G, equivalent to 3.36 kg AI/ha, in furrow at...
Potatoes were grown during 1992 in 2 m2 plots of loam which had received 1, 2 or 3 annual treatments of Di-Syston 15G, equivalent to 3.36 kg AI/ha, in furrow at planting. The presence of enhanced degradative activity to the sulfoxide and sulfone metabolites of disulfoton in the soil treated in the previous two years was confirmed by laboratory tests prior to the 1992 treatments. Soil, seed potato and foliage from the three treatments were analyzed for disulfoton and its sulfoxide and sulfone metabolites for 12 wk following planting/treatment. Disulfoton was the major insecticidal component of the soil, a minor component of the seed piece and was not detected (< 0.02 ppm) in potato foliage. Disulfoton concentrations in each of the three substrates sampled were similar for the three treatments. Disulfoton sulfoxide and sulfone were the major insecticidal components of the seed piece and foliage. Their maximum concentrations in 1st year soil, seed pieces and foliage were ca. 2x, 2x and 6x, respectively, those measured in the 2nd and 3rd year treatments. The results demonstrate that enhanced microbial degradation of relatively minor insecticidal compounds in the soil can profoundly affect insecticide levels in the plant when these compounds are the major insecticidal components accumulated. The broader implications for crop protection using soil-applied systemic insecticides are discussed.
Topics: Biodegradation, Environmental; Disulfoton; Food Contamination; Soil Microbiology; Soil Pollutants; Solanum tuberosum
PubMed: 8201175
DOI: 10.1080/03601239409372892 -
Journal of the Science of Food and... Feb 1967
Topics: Insecticides; Soil
PubMed: 6040855
DOI: 10.1002/jsfa.2740180208