Methoxychlor dealkylation

Methoxychlor is degraded in vivo by 0-dealkylation and excreted as mono-and bis-phenols. It is much less environmentally persistent also much less toxic to rats (oral LD q> 6000 mg/Kg compared with LD q 118 mg/Kg for DDT Metcalf, ref. 16). However, methoxychlor toxicity in fish approaches that of DDT, and in cold water fish, e.g., Atlantic salmon, it can accumulate to excessive levels. Although much less toxic in mammals than DDT it is similar in its estrogenic action. Methylchlor is less toxic to fish than methoxychlor, but also rather ineffectual as an insecticide. Comparison of the persistence characteristics of the methyl and methoxy analogs of DDT shows the microsomal side chain oxidation of the alkyl group to be more efficient than microsomal 0-dealkylation. 

Many xenobiotics contain alkyl groups, such as the methyl (-CH3) group, attached to atoms of O, N, and S. An important step in the metabolism of many of these compounds is replacement of alkyl groups by H, as shown in Figure 7.6. These reactions are carried out by mixed-function oxidase enzyme systems. Examples of these kinds of reactions with xenobiotics include O-dealky-lation of methoxychlor insecticides, N-dealkylation of carbary 1 insecticide, and S-dealkylation of dimethyl mercaptan. Organophosphate esters (see Chapter 18) also undergo hydrolysis, as shown in Reaction 7.3.12 for the plant systemic insecticide demeton ... 

O-Dealkylation O-Dealkylation of alkyl groups of the ester or ether structures of insecticides occurs frequently, but it also involves an unstable a-hydroxy intermediate as found in N-dealkylation. For example, methoxychlor is O-demethylated by the system (Figure 8.6). O-Dealkylation is known to occur with a wide variety of organophosphates, including certain dimethyl triesters. O-Dealkylation results in detoxification. 

The dealkylation of methoxychlor, which is an example of O-dealkylation, has also been observed in anaerobic soils (Equation 3.47)... 

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