Metabolism 6-Halogen substitution

Hughes DE (1965) The metabolism of halogen-substituted benzoic acids by Pseudomonas fluorescens. Biochem J 96 181-188. 

Ahlborg, U. G. Thurnberg, T. M. (1980). Chlorinated phenols occurrence, toxicity, metabolism, and environmental impact. Critical Reviews in Toxicology, 7, 1-35. Allard, A-S., Remberger, M. Neilson, A. H. (1987). Bacterial O-methylation of halogen substituted phenols. Applied and Environmental Microbiology, 53, 839—45. 

A comprehensive review of the metabolism of PCBs was published in 1976 by Sundstrom et al. (ref. 139a) confirming the importance of degree of substitution and location of halogens on toxicity. The lesser chlorinated biphenyls are more readily metabolized. The presence of at least two adjacent hydrogens—preferably in positions 3. 4, 5 or 3, 4, 5 —is required for the rapid metabolism of PCBs. This requirement is satisfied by all mono-, di- and trichlorobiphenyls, and by the tetrachlorobiphenyls with the exception of the 3. 3. 5. 5 -chlorinated PCB. This compound was reported particularly toxic to monkeys, and the intermediate formation of chlorinated dibenzofuran was postulated to account for this toxicity (ref. 139c). 

Some of the substitution reactions, mainly at the indole-nitrogen as well as halogenation at C-2 have already been discussed in Volume VIII. Oxidation of 2,3-dihydrolysergic acid derivatives with Fremy s salt leads to derivatives of 12-hydroxylysergic acid (41) which have recently been shown to be significant in metabolic studies (41a). 

Because NAC is a natural compound that contains no halogen atoms or substitutions, it would be expected to be easily metabolized by microorganisms in the environment and thus not present a risk from the standpoint of persistence or bioaccumulation. 

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