Oxamyl studies

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

Figure 1 was taken from an unpublished report, DuPont Study No. AMR 4392-97, Dissipation of Dislodgeable Foliar and Soil Residues of Oxamyl Following Application of Vydate L Insecticide to Tomatoes in the USA - Season 1997-1998 . This study has been submitted to the EPA and the data were used to establish and verify re-entry intervals. Data from this study will be used to provide an example of the topics discussed throughout this article. 

In the oxamyl tomato study, the DFR samples were obtained using a 5-cm Birkestrand sampler (10-cm disk size using the upper and lower surfaces). The sample consisted of 40 leaf disks or 400 cm from each subplot. The samples were collected impartially or in a nondirected approach from the middle two rows. The plot was four rows wide and the tractor came into contact with the first and fourth rows as the application was made. The middle two rows should be undisturbed by this movement and should therefore provide a more representative sample. 

Field recovery samples are an important part of the quality control in DFR studies. Field fortifications allow the experimental data to be corrected for losses at all phases of the study from collection through sample transport and storage. Fresh laboratory fortifications monitor losses due to the analytical phase. This section details how the field recovery process was handled in the oxamyl tomato DFR study. 

Fresh oxamyl standards were prepared for each fortification event. Concentrations of 50 and 400 qg mL analytical-grade oxamyl were prepared in a 20% acetonitrile-80% FIPLC-grade water solution. The solutions were tranferred in 1-mL aliquots into uniquely identified vials so that each vial contained the correct volume of oxamyl standard to fortify one quality control sample. The vials were shipped as needed during the course of the study to each field site. 

A reproducibility study of two series of 10 solutions containing 1000 and 2500pg of Oxamyl, respectively, gave an arithmetic mean, standard deviation and coefficient of variation of 997pg, 8.0pg and 0.80%, respectively, for the first series and 2489pg, 13.3pg and 0.53%, respectively, for the second. The average recovery varied from 85.5-100.8%. 

Kennedy, G.D., Jr. Acute toxicity studies with oxamyl, Fundam. Appl. Toxicol., 6(3) 423-429, 1986. 

The first objective has been accomplished by the development of an HPLC procedure as reported by Spalik et al. ( 5) and GC/NPD procedures developed by Lemley and Zhong ( ). The second and third objectives are being accomplished by fundamental solution studies and reactive ion exchange experiments conducted in parallel. Lemley and Zhong (7) determined recently the solution kinetics data for base hydrolysis of aldicarb and its oxidative metabolites at ppm concentrations and for acid hydrolysis of aldicarb sulfone. They have since ( ) reported similar results for ppb solutions of aldicarb and its metabolites. In addition, the effect on base hydrolysis of temperature and chlorination was studied and the effect of using actual well water as compared to distilled water was determined. Similar base hydrolysis data for carbofuran, methomyl and oxamyl will be presented in this work. 

Materials. Aldicarb standards were obtained from the United States Environmental Protection Agency (USEPA), Quality Assurance Section and from Union Carbide Corporation. Crystalline samples of carbofuran and 3-hydroxycarbofuran were supplied by the Agricultural Chemical Group of FMC Corporation. Reference standards of methomyl (99% pure) and oxamyl (99% pure) were obtained from USEPA. HPLC grade methanol was purchased from Burdick and Jackson, Inc. Methylene chloride used for bulk extractions of the carbamate pesticides in solution was recovered, distilled and reused. Analytical reagent grade chemicals and solvents were used in all experiments. Doubly distilled deionized water was used for solution rate studies. Deionized distilled water (DDW) was used for dilutions in reactive ion exchange experim ts., , ... 

Another lab study (102) using a loamy sand (pH 6.8) and a fine sand (pH 6.4) showed oxamyl half-lives of 11 and 15 days under aerobic conditions, respectively. There were no extract-able degradation products. However, under anaerobic conditions, a half-life of 6 days was found and extractable degradation products persisted (102). 

Edgington and Peterson (4) have subdivided apoplastic xeno-biotics into two classes. Euapoplastic (only transported in the apoplast) and pseudoapoplastic (transport occurs mainly in the xylem but entry into the symplast occurs). Most traditional "apoplastic" chemicals are now known to really be pseudoapoplastic chemicals, e.g., atrazine, diuron, oxamyl, etc. The unresolved question is why don t these pseudoapoplastic chemicals which cross the cell membranes and enter the symplast remain in the symplasm of the phloem There have been numerous studies focusing on the molecular requirements for phloem mobility (1-5), In general, there is not a good correlation between phloem mobility and water solubility, metabolism of the xenobiotic, or the presence of various substitution groups in a molecule. 

Caibamate pesticides are used as insecticide, acaricide, and herbicide. Various subclasses can be distinguished. Aryl V-methyl carbamates (1), such as caibaiyl, carbofuran, propoxur, and oxime V-methyl carbamates(2), such as aldicaib, methomyl, oxamyl, have most widely been studied. LC-MS is the method-of-choice for carbamates, since their thermal lability prohibits GC analysis. 

The World Health Organization (WHO) (15), in 1981, set a temporary ADI for oxamyl based on a no-effect level from a 2-year dog study. The Committee expressed concern, however, that the dog is somewhat less sensitive to oxamyl than the rat and that a clear no-effect level had not been established in the rat. Additional concern was expressed over the lack of identification of 50% of the tissue residues of oxamyl. The WHO was requiring that by 1983 tissue residues be identified and that the no-effect level in the rat be clarified. Based on the WHO temporary ADI, a drinking water guideline of 70 ug/1 can be calculated. 

The results of a study of carbofuran treatment intensity on the cross enhancement factors for carbaryl, cloethocarb and oxamyl are... 

Soil The sulfoxide group is oxidized to the sulfone and oxidative and hydrolytic cleavage of the side chain gives dimethylphosphoric and phosphoric acids (Hartley and Kidd, 1987). Oxamyl was degraded by the microorganism Pseudomonas putida in a laboratory study using cultured bacteria (Zeigler, 1980). 

Newsome et al. [974] studied the chromatography of 11 carbamate pesticides (e.g., aldicaib, aldicarb sulfoxide and sulfone, oxamyl, cathofiiran, 3-hydroxy- and 3-ketocaiboiuran) on a Cg column. A postcolumn o-phthalaldehyde derivatization technique (A = 336 run, ex 440 nm, em) was compared with an atmospheric pressure ionization MS detector. A 20-min 12/78 -> 70/30 acetonitrile/water gradient generated good resolution and peak shapes. Detection limits forall compounds were tabulated and were 0.1 ng for fluorescence and 1 ng for APCl/MS. 

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