Mechanistic aspects of ingested chlorine dioxide on thyroid function: impact of oxidants on iodide metabolism.

Abstract

Toxicological studies dealing with recent findings of health effects of drinking water disinfectants are reviewed. Experiments with monkeys and rodents indicate that the biological activity of ingested disinfectants is expressed via their chemical interaction with the mucosal epithelia, secretory products, and nutritional contents of the alimentary tract. Evidence exists that a principal partner of this redox interaction is the iodide of nutritional origin that is ubiquitous in the gastrointestinal tract. Thus the observation that subchronic exposure to chlorine dioxide (ClO2) in drinking water decreases serum thyroxine levels in mammalian species can be best explained with changes produced in the chemical form of the bioavailable iodide. Ongoing and previously reported mechanistic studies indicate that oxidizing agents such as chlorine-based disinfectants oxidize the basal iodide content of the gastrointestinal tract. The resulting reactive iodine species readily attaches to organic matter by covalent bonding. Evidence suggests that the extent to which such iodinated organics are formed is proportional to the magnitude of the electromotive force and stoichiometry of the redox couple between iodide and the disinfectant. Because the extent of thyroid uptake of the bioavailable iodide does not decrease during ClO2 ingestion, it seems that ClO2 does not cause iodide deficiency of sufficient magnitude to account for the decrease in hormonogenesis. Absorption of one or more of iodinated molecules, e.g., nutrients, hormones, or cellular constituents of the alimentary tract having thyromimetic or thyroid inhibitory properties, is a better hypothesis for the effects seen.ImagesFIGURE 1. aFIGURE 1. bFIGURE 1. c

Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action

“…Fig. 2 provides a comparison of the rat and human hormonal maintenance of the In vivo positive studies In vivo negative studies MOA data in rats, possibility through oxidation of dietary iodide in the GI tract, resulting in reactive species that iodinate organic matter to form potentially thyroid inhibitory compounds (Bercz et al, 1986;Orme et al, 1985) Chlorite SD rat, DW, GD7-14, also maternal toxicity (body weight loss and hemolysis) and greatly decreased water and food intake; only 5 rats/ group (Couri et al, 1982) SD rat, DW, fertility not affected (Gill et al, 2000) Generally, toxicity is considered due to oxidative properties (U.S. EPA, 2000b) Suggestive data:…”

“…Chlorine dioxide-disinfected DW Suggestive data: Human, DW, epi (Kallen and Robert, 2000) ---Human, DW, epi (Cedergren et al, 2002) Chlorine dioxide Rat, DW, but only 6-8 dams/ dose (Suh et al, 1983) --Generally, toxicity is considered due to oxidative properties (U.S. EPA, 2000b). Decreased the levels of circulating thyroxine in monkeys and rats, and in developmental study in rats, possibly though oxidation of dietary iodide in the GI tract, resulting in reactive species that iodinate organic matter to form potentially thyroid inhibitory compounds (Bercz et al, 1986;Orme et al, 1985). Chlorite -SD rat, DW, but only 6-8 dams/ dose, MTD not achieved (Suh et al, 1983) --Generally, toxicity is considered due to oxidative properties (U.S. EPA, 2000b).…”

“…Rat, DW, but examined external malformations during lactational period (Carlton et al, 1991) Decreased the levels of circulating thyroxine in monkeys and rats, and in developmental study in rats, possibly though oxidation of dietary iodide in the gastrointestinal tract, resulting in reactive species that iodinate organic matter to form potentially thyroid inhibitory compounds (Bercz et al, 1986;Orme et al, 1985) (continued on next page) (Suh et al, 1983) --Generally, toxicity is considered due to oxidative properties (U.S. EPA, 2000b). Rabbit, DW, MTD may not have been achieved (Harrington et al, 1995).…”

Subchronic Sodium Chlorate Exposure in Drinking Water Results in a Concentration-Dependent Increase in Rat Thyroid Follicular Cell Hyperplasia

“…In a subsequent study, Harrington, Shertzer, and Bercz (17) noted a decrease in T 4 levels in both rats and monkeys exposed to drinking water containing 0.1 g/L ClO 2 . Decreased T 4 levels are associated with increased binding of dietary iodide to gastrointestinal tissue and contents (5,10,16). These observations led to the hypothesis that ClO 2 oxidizes iodine in food to a reactive species that binds to tissues of the digestive tract preventing absorption of dietary iodide.…”

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

“…l -1 were associated with a significant increase in follicular epithelial cell height and a significant frequency distribution shift to the higher height categories. These results suggest antithyroidal effects of chlorine or chlorinated products formed when chlorine reacts with organic matter in the upper gastrointestinal tract as it is presumed in pigeons (Revis et al 1986) or the effects of some iodinated molecule forming in trace quantities in the alimentary tract responsible for the thyroid inhibition during chlorine dioxide exposure (Bercz et al 1986). It has also been shown (Bercz et al 1982;Orme et al 1985) that decreased serum thyroxin levels occur in monkeys and neonatal rats during subchronic exposure to chlorine dioxide in drinking water.…”