Oximes toxicity

Novichok agents Agents produce HF, HCl, or HCN when hydrolyzed. They may also produce highly toxic oximes. 

There are no obvious differences in sensitivity among small laboratory animals. Figure 7 compares the LD50 data of various oximes after IM administration to various animals. It is clear that, on a molar basis, methoxime has the lowest LD 50 while HI 6 is probably the least toxic oxime. 

Ivermectin is the catalytic reduction product of avermectin, a macroHde containing a spiroketal ring system. Two other related antibiotics having significantly different stmctural features and biological properties, moxidectin and milbemycin oxime, were more recentiy introduced into the market. Although these compounds have no antimicrobial activity, they are sometimes referred to as antibiotics because they are derived from fermentation products and have very selective toxicities. They have potent activity against worms or helminths and certain ectoparasites such as mites and ticks. 

Oxime carbamates are generally applied either directly to the tilled soil or sprayed on crops. One of the advantages of oxime carbamates is their short persistence on plants. They are readily degraded into their metabolites shortly after application. However, some of these metabolites have insecticidal properties even more potent than those of the parent compound. For example, the oxidative product of aldicarb is aldicarb sulfoxide, which is observed to be 10-20 times more active as a cholinesterase inhibitor than aldicarb. Other oxime carbamates (e.g., methomyl) have degradates which show no insecticidal activity, have low to negligible ecotoxicity and mammalian toxicity relative to the parent, and are normally nondetectable in crops. Therefore, the residue definition may include the parent oxime carbamate (e.g., methomyl) or parent and metabolites (e.g., aldicarb and its sulfoxide and sulfone metabolites). The tolerance or maximum residue limit (MRL) of pesticides on any food commodity is based on the highest residue concentration detected on mature crops at harvest or the LOQ of the method submitted for enforcement purposes if no detectable residues are found. For example, the tolerances of methomyl in US food commodities range from 0.1 to 6 mg kg for food items and up to 40 mg kg for feed items. ... 

The agents in this class are halogenated oximes. This class of agents is not specifically covered by the Chemical Weapons Convention. Because of the toxicity of the agents and lack of commercial application outside of limited scientific research, urticants would be prohibited based on the Guidelines for Schedules of Chemicals. 

Human toxicity values have not been established or have not been published. However, this material is a much less powerful irritant than Phosgene oxime (C05-A001). 

Agency for Toxic Substances and Disease Registry. "Phosgene Oxime ToxFAQs." April 2002. 

Lieske CN, Clark JH, Maxwell DM, et al Studies of the amplification of carbaryl toxicity by various oximes. Toxicol Lett 62 127-137, 1992... 

Tin-based reagents are not always snitable owing to the toxicity of organotin derivatives and the difficulties often encountered in removing tin residues from the final product. Therefore, the same authors have carried out additional experiments with 17d and several different alkyl halides under tin-free conditions. The treatment of 16d with tert-butyldiphenylsilyl chloride (TBDPSCl) and triethylamine in the presence of silver triflate in CH2CI2 affords the bis(silyloxy)enamine 17d in 92% yield (Scheme 17). When the radical reaction was carried out with ethyl iodoacetate in the presence of 2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as the initiator in CH2CI2, the oxime ether 19 was obtained in 83% yield (Scheme 17). 

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 . ... 

Toxicity studies with noncharged oximes, such as methyl ethyl ketoxime, showed that 300-900 mgkg produced reversible neurobehavioral changes that were attributed to CNS depression ". Significant depression of locomotor activity was reported already with 30 mgkg of indole-3-aldoxime, and increasing the dose to 120 mgkg produced... 

It is important to note that the computed potential energy surface reveals a facile reactivation via Scheme 7, with low energy barriers both in the gas phase and in aqueous solution" . This accords with experimental findings on oximates as reactivators following poisoning by organophosphorus toxics. 

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