Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Sarin metabolites

Sarin and its corresponding nontoxic hydrolysis products (IMPA, and additional methyl phosphonic acids) are predominantly eliminated via the kidneys which are thus more important for detoxification than the liver (Little et al, 1986 Waser and Streichenberg, 1988). Urinary excretion happens quite rapidly as demonstrated for single dose s.c. application of sarin, cyclosarin, and soman to rats (Shih et al, 1994). The terminal elimination half-life was found to be 3.7 =E 0.1 h for sarin and 9.9 0.8 h for cyclosarin. In contrast soman showed a biphasic elimination with terminal half-fives of about 18.5 h and 3.6 h (Shih et al, 1994). Maximum peak levels of sarin metabolites in urine were detected 10-18 h after exposure (Minami et al, 1997) and after 2 days hydrolyzed sarin metabolites had been excreted nearly quantitatively (Shih et al, 1994). In contrast, even at 5 days post-exposure soman metabolite recovery was only 62% (Shih et al, 1994). Excretion of soman from blood, fiver, and kidney compartments following cfiemical and enzymatic hydrolysis is considered a first-order elimination process (Sweeney et al, 2006). [Pg.771]

Shih and colleagues (1994) injected rats subcutaneously with a single dose of sarin (75 ftg/kg) and measured excretion of the hydrolyzed metabolites, the alkylmethylphos-phonic acids, including IMPA and other methylphosphonic acids. Urinary elimination was found to be quite rapid and the terminal elimination half-life of sarin metabolites in urine was 3.7 h. Most of the administered dose of sarin was retrieved from the urine in metabolite form after 2 days. [Pg.800]

Distribution, metabolism, and elimination of sarin in humans appear to resemble findings in animals. Minami and colleagues (1997, 1998) detected the sarin metabolite IMPA in urine of humans after the terrorist attack in Tokyo in 1995. They found peak levels of IMPA or methylphosphonic acid in urine 10-18 h after exposure. The levels of IMPA in urine correlated with the clinical symptoms. They also found evidence of distribution of sarin to the human brain in four of the 12 people who died after exposure. IMPA and MPA were detected in patients from the Matsumoto sarin exposure (Nakajima et al, 1998). [Pg.800]

Although the police investigation collected enough evidence to prove that sarin was used by AUM Shinrikyo terrorists in Tokyo, the final scientific proof came this summer, when two laboratories independently determined sarin metabolites in blood and urine samples drawn from Tokyo subway attack victims. The Holland group of investigators liberated them from plasma butyrylcholineste-rases [14], while the Japanese group used urine instead [30],... [Pg.110]

Shih et al. (1994) injected rats subcutaneously with a single dose of 75]Hg/kg of sarin, cyclosarin, and soman, and measured excretion of the hydrolyzed metabolites and the alkylmethylphosphonic acids, including IMPA and corresponding MPAs. MPA was a major and common metabolite of the three compounds. Urinary excretion over the first 24 h accounted for approximately 90% of the administered doses of sarin and cyclosarin. Almost total recoveries of the given doses for sarin and cyclosarin in metabolite form were obtained from the urine. Urinary elimination was found to be rapid and the terminal elimination half-life of sarin metabolites in urine was 3.7h. Most of the administered dose of sarin was retrieved from the urine in a metabolite form after 2 days. The terminal elimination half-life of cyclosarin in urine was 9.9 h. Soman metabolite showed a biphasic elimination curve with terminal half-lives of 18.5 and 3.6 h. Soman was excreted at a slower rate, with a recovery of only 62%. The first phase of elimination of soman results from enzymatic hydrolysis of the inactive P( + ) isomers, and the slower phase is from the active P( - ) isomers (Benschop and De Jong, 1991). The elimination study in rats determined IMPA in blood up to 14 h after exposure, CHMPA up to 2 days, and PMPA up to at least 3 days. [Pg.885]

IMPA, the major metabolite of diisopropyl methylphosphonate, has been suggested as a possible biomarker of exposure for diisopropyl methylphosphonate. The excretion of IMPA is not unique to diisopropyl methylphosphonate exposure IMPA is also a major metabolite of GB (Sarin) (Little et al. [Pg.98]

Diisopropyl methylphosphonate is an organophosphate compound that was first produced in the United States as a by-product of the manufacture of the nerve gas isopropyl methylphosphonofluoridate (GB, or Sarin) (ATSDR 1996 EPA 1989 Robson 1977, 1981). It is not a nerve gas and is not a metabolite or degradation product (Roberts et al. 1995). Diisopropyl methylphosphonate constitutes approximately 2-3% of the crude GB product, but it is neither a metabolite nor a degradation product of GB (EPA 1989 Rosenblatt et al. 1975b). Diisopropyl methylphosphonate is not normally produced except for its use in research. One method of producing diisopropyl methylphosphonate is to combine triisopropyl phosphite and methyl iodide. The mixture is then boiled, refluxed, and distilled, yielding diisopropyl methylphosphonate and isopropyl iodide (Ford-Moore and Perry 1951). Diisopropyl methylphosphonate may also be prepared from sodium isopropyl methylphosphonate by a reaction at 270° C, but a portion of the resulting diisopropyl methylphosphonate is converted to trimethylphosphine oxide at this temperature (EPA 1989). [Pg.114]

Exposure. No biomarkers of exposure were identified that were specific to diisopropyl methylphosphonate. Although standard procedures exist for identifying diisopropyl methylphosphonate s primary metabolite (IMP A) in plasma, urine, and feces (Weiss et al. 1994), the detection of IMP A is not unique to diisopropyl methylphosphonate exposure. IMPA is also a major metabolite of GB (Sarin) (Little et al. 1986). In addition, IMPA is cleared from the body rapidly, making it a useful indicator for recent exposure only. [Pg.139]

Little PJ, Reynolds ML, Bowman ER, et al. 1986. Tissue disposition of (3H)sarin and its metabolites in mice. Toxicol Appl Pharmacol 83(3) 412-419. [Pg.151]

Little PJ, Scimeca JA, Martin BR. 1988. Distribution of (3H)diisopropyl flourophosphate, (3H)soman, (3H)sarin, and their metabolites in mouse brain. Drug Metab Dispos 16(4) 515-520. [Pg.151]

Heavy metals, arsenic speciation, mercury speciation, organophosphates, organochlo-rine pesticides, VOCs, dichloroethane, trichloroethylene cotinine, nitrates and nitrites, creosote, PAHs (wood smoke), radionuclides, cyanide, dioxin-furan, disinfection byproducts, perchlorates, phthalate metabolites, thiodiglycol (mustard gas), sarin... [Pg.62]

Minami, D.M. Hui, M. Kasumata, H. Inagaki and C.A. Boulet, Method for the analysis of the methylphosphonic acid metabolites of sarin and its ethanol-substituted analoque in urine as applied... [Pg.196]

VX appears to follow a similar pathway, the major metabolite being ethyl MPA (EMPA). An additional metabolite, derived from the diisopropy-laminoethyl substituent, was identified in human plasma following an assassination with VX (45). The sulfide (17), derived from enzymatic S-methylation of the hydrolysis product HSCH2CH2N(i-Pr)2, was identified in human serum by GC/MS after simple extraction. Experiments in rats confirmed the rapid metabolic formation of (17) from HSCH2CH2N(i-Pr)2 (46). Identification of this metabolite distinguishes VX from the O-ethyl analogue of sarin. [Pg.419]

T. Nakajima, K. Sasaki, H. Ozawa, Y. Sekijima, H. Morita, Y. Fukushima and N. Yanagisawa, Urinary metabolites of sarin in a patient of the Matsumoto sarin incident, Arch. Toxicol., 72, 601-603 (1998). [Pg.429]

Shih, M.L., McMonagle, J.D., Dolzine, T.W., Gresham, V.C. (1994). Metabolite pharmacokinetics of soman, sarin and GF in rats and biological monitoring of exposure to toxic OP agents. J. Appl Toxicol. 14 195-9. [Pg.788]

In addition, due to the reversibility of the binding reaction of sarin and soman to CarbE, it appears that CarbEs are involved in metabolic detoxification of these agents to their corresponding nontoxic metabolites isopropyl methylphosphonic acid (IMPA) and pinacolyl methylphosphonic acid (PMPA) (Jokanovic et al, 1996). [Pg.799]

FIGURE 52.1. Metabolic detoxification of warfare nerve agents tabun, sarin, soman, and VX in mammals in vivo. Chemical names of metabolites are EDMPA - ethyl dimethylaminophosphoric acid, IMPA - isopropyl methylphosphonic acid, PMPA - pinacolyl methyl-phosphonic acid, EMPA - ethyl methylphosphonic acid, and MPA - methylphosphonic acid. [Pg.800]

Barr, J.R., Driskell, W.J., Aston, L.S., Martinez, R.A. (2004). Quantitation of metabolites of the nerve agents sarin, soman, cyclohexylsarin, VX and Russian VX in human urine using isotope-dilution gas chromatography-mass spectrometry. J. Anal. Toxicol. 28 372-8. [Pg.833]

Evans, R.A., Jakubowski, E.M., Muse, W.T., Matson, K., Hulet, S.W., Mioduszewski, R.J., Thomson, S.A., Totura, A.L., Retmer, J.A., Crouse, C.L. (2008). Quantification of sarin and cyclosarin metabolites isopropyl methylphosphonic acid and cyclohexyl methylphosphonic acid in minipig plasma using isotope-dilution and liquid chromatography-time-of-flight mass spectrometry. J. Anal. Toxicol. 32(1) 78-85. [Pg.834]


See other pages where Sarin metabolites is mentioned: [Pg.800]    [Pg.800]    [Pg.300]    [Pg.118]    [Pg.276]    [Pg.291]    [Pg.404]    [Pg.418]    [Pg.426]    [Pg.677]    [Pg.736]    [Pg.761]    [Pg.765]    [Pg.787]    [Pg.805]    [Pg.806]    [Pg.809]    [Pg.809]    [Pg.880]    [Pg.1023]    [Pg.1039]    [Pg.25]    [Pg.154]    [Pg.91]    [Pg.501]   
See also in sourсe #XX -- [ Pg.139 ]




SEARCH



Sarin

© 2024 chempedia.info