Endocrine Toxicity of Drinking Water Disinfectants. II. Inhibition of Hepatic 5'-Thyroxine Deiodinase by Halogenated Nutrients

Abstract

Administration of drinking water treated with chlorine-based disinfectants was shown in prior studies to interfere with thyroid function of laboratory animals. One possible mechanism is that intraalimentary redox interactions between chlorine oxides and organic and inorganic contents of the gastrointestinal tract cause formation of iodinated and chlorinated nutrients. Several halogenated organic molecules generated by this route were shown to vary in their in vivo dehalogenation and clearance. In seeking clues to the etiology of the thyroid effect, the influence of several iodinated and chlorinated amino and fatty acid isomers on 5-deiodination of thyroxine (T₄) to triiodothyronine (T₃) was studied using rat liver homogenates in this study. Several of the compounds tested inhibited conversion of T₄ to T₃, with effective concentration comparable to the known inhibitor of the type I 5'-thyroxine deiodinase (5'-TDI). Unexpectedly, iodinated isomers of histidine, and chlorotyrosine appeared to activate rather than decrease T₃ formation. Effective molar concentrations indicated that even if all of the chlorine dose ingested via drinking water would be converted into such halogenated analogs, their levels in body fluids would be too small to cause clinically detectable thyroid changes.

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