Toxicity carbamates

Edmiston, C.E., Jr., Goheen, M., Malaney, G.W., and Mills, W.E. Evaluation of carbamate toxicity acute toxicity in a culture of Paramecium multlmlcronucleatum upon exposure to aldicarb, carbaryl, and mexacarbate as measured by a Warburg respirometry and acute plate assay. Environ. Res., 36(2) 338-350, 1985. 

Wolfe. M.F., Villalobos. S.A., Seiber, J.N., and Hinton, D.E. A comparison of carbamate toxicity to medaka (Oryzias latiped) embryos and larvae. Toxicologist, 13(1) 268, 1993. 

In contrast to the beneficial effects of treatment with oximes in cases of OP intoxication, reports in the literatnre suggest that treatment of poisoning with certain anticholinesterase carbamates with some oximes should be avoided because they may actually potentiate carbamate action. Other oximes decrease carbamate toxicity. The effects observed are, in general, correlated with changes in the rates of carbamylation and decarbamylation in the presence of the various oximes . ... 

Gupta RC and Dettbarn WD (1993) Role of carboxylest-erases in the prevention and potentiation of N-methyl-carbamate toxicity. Chemico-Biological Interactions 87 295-303. 

Sharma R, Komatsu S, Noda H. Proteomic analysis of brown planthopper Application to the study of carbamate toxicity. Insect Biochem Mol Biol 2004 34(5) 425-32. 

Loewenstein, Y., Dcnarie, M., Zakut, H., and Soreq, H. (1993). Molecular dissection of cholinesterase domains responsible for carbamate toxicity. Chem.-Biol. Interact. 87, 209-216. 

Gupta, R. C,. Dettbam, W-D., Sanecki, R. K., and Goad, J. T, (1999). Biochenticai and microscopic changes in diaphragm muscle by acute carbamate toxicity. Toxicol. Sci. 48, 188, [Abstract]... 

In both mouse (n = 14) and chicken (n = 8) oral toxicities, the only discernible factor is a strong positive dependence on H-bonding groups (1.01 HB, 0.98 HB). None of the mechanistic factors were significant for these small sets. Active site binding is the principal mechanistic step in carbamate toxicity. 

The effect of administration route on drug action is discussed in some detail by Benet (19) and by Rowland (20). Oral administration forces a first-pass route through the liver, subjecting the toxicant to enhanced metabolism. Other routes are weaker metabolically, though in some cases, skin can display up to 80% or more of liver metabolite activity. In the rat, for example, skin is more efficient than liver in degrading aryl carbamates. Our results support this thesis in terms of mean Log MW/LD50 values for phenol toxicity but not for carbamate toxicity. 

Hoffman RS, Manini AF, Russell-Haders AL, Felberbaum M, Mercurio-Zappala M. Use of prahdoxime without atropine in rivastigmine (carbamate) toxicity. Hum Exp Toxicol 2009 28 599-602. 

Use of oximes is well accepted for OP exposures, but their role in carbamate poisoning is controversial. Animal studies have shown oxime use can increase toxicity when treating carbaryl exposure (Lifshitz et al., 1994). Therefore, there is a general guideline that oximes should be avoided if a carbamate exposure is suspected. One case series reported the routine use of oxime therapy for carbamate exposures in children (Lifshitz et al., 1994). Marked clinical improvement was observed in all patients, regardless of whether they were exposed to an OP or a carbamate. In addition to the retrospective review of cases, the authors completed an in vitro study of oxime use with carbamate toxicity and discovered that oximes play a minor role in direct reactivation of human carbamylated AChE. Due to this finding, the authors concluded that the current guideline to avoid oxime use in a carbamate exposure is valid. 

Fortunately, in most cases of OP or carbamate toxicity, pediatric patients recovered fully if they were diagnosed rapidly and appropriate treatments were administered in a timely fashion. 

Environmental. The A/-methylcarbamates generally are biodegradable and of low soil persistence with half-Hves for carbaryl and aldicarb of 1—2 weeks and of carbofuran of 1—4 months. Certain carbamates are highly toxic to birds with oral LD qS for mallard, eg, pheasant, in mg/kg carbofuran, 0.40, 4.2 mexacarbate, 3.0, 4.5 and methomyl, 16, 15 compared to carbaryl >2000. Fish toxicity of carbamates is generally low, but these compounds are extremely toxic to bees. In cases of human poisoning, atropine is a specific antidote. 

The extremely toxic and flammable gas phosphine is safely and conveniently generated for the fumigation of grain in sacks or bins from 3-g tablets containing aluminum phosphide and ammonium carbamate which produce 1 g of phosphine in the presence of moisture. 

Naphthol is mainly used in the manufacture of the insecticide carbaryl (59), l-naphthyl A/-methyicarbamate/ iJ-2j5 - (Sevin) (22), which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate is usually prepared by treating methylamine with phosgene. Methyl isocyanate is a very toxic Hquid, boiling at 38°C, and should not be stored for long periods of time (Bhopal accident, India). India has developed a process for the preparation of aryl esters of A/-alkyl carbamic acids. Thus l-naphthyl methylcarbamate is prepared by refluxing 1-naphthol with ethyl methylcarbamate and POCl in toluene (60). In 1992, carbaryl production totaled > 11.4 x 10 t(35). Rhc ne-Poulenc, at its Institute, W. Va., facihty is the only carbaryl producer in United States. 

The mechanism of this reaction has been studied by several groups [133,174-177]. The consensus is that interaction of ester with the phenolic resole leads to a quinone methide at relatively low temperature. The quinone methide then reacts rapidly leading to cure. Scheme 11 shows the mechanism that we believe is operative. This mechanism is also supported by the work of Lemon, Murray, and Conner. It is challenged by Pizzi et al. Murray has made the most complete study available in the literature [133]. Ester accelerators include cyclic esters (such as y-butyrolactone and propylene carbonate), aliphatic esters (especially methyl formate and triacetin), aromatic esters (phthalates) and phenolic-resin esters [178]. Carbamates give analogous results but may raise toxicity concerns not usually seen with esters. 

CARBAMATE PESTICIDES, FLAMMABLE, LIQUID, TOXIC, n.O.S., CARBAMATE PESTICIDES, FLAMMABLE, LIQUID, TOXIC, n.O.S.,... 

The insecticide carbaryl can be produced by several routes, some of which do not use methyl isocyanate, or which generate only small quantities of this toxic material as an in-process intermediate (Kletz, 1991b). One company has developed a proprietary process for manufacture of carbamate insecticides which generates methyl isocyanate as an in-situ intermediate. Total methyl isocyanate inventory in the process is no more than 10 kilograms (Kharbanda and Stallworthy, 1988 Manzer, 1994). 

Cable GG, Doherty S. 1999. Acute carbamate and organochlorine toxicity causing convulsions in an agricultural pilot A case report. Aviat Space Environ Med 70(l) 68-72. 

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