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.

Toxicology of drinking water disinfection byproducts from nutrients. Rate studies of destruction of polyunsaturated fatty acids in vitro by chlorine-based disinfectants

“…Halogenated nutrients including chlorinated fatty acids have been demonstrated in vitro to affect hepatic 5'-thyroxine deiodinase activity (9).…”

“…The presence of cigarette smoke in the lung also causes increased concentrations of neutrophils, suggesting that emphysematous lesions may result from the destruction of lung tissue by these cells (6). Both PAM and neutrophils are capable of producing and releasing nitric oxide (NO) and Of (7)(8)(9), which could react to form peroxynitrite2 ****(0=NOO~), a powerful oxidant (10,11).…”

The Effects of Chlorine Intake on Some Morphometric Parameters of the Thyroid Gland in Lambs

“…The disinfection of potable water with chlorine-based disinfectants represents the most dominant class of inorganic xenobiotics ingested continuously (Bercz and Garner 1991). The chlorine-based disinfectants have been reported occasionally to affect the endocrine homeostasis and thyroid hormone levels in blood in animals.…”