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The Iodine Group | |
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THRALL
Evidence of thyroxine formation following iodine administration in Sprague-Dawley rats.Thrall KD, Sauer RL, Bull RJ. J Toxicol Environ Health. 1992 Dec;37(4):535-48. [abstract only]
"Iodine (I2) has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of I2 to Sprague-Dawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4/T3) levels. This is not observed with iodide (I-) treatment. The present study addresses the possibility that I2 reacts with deiodinated T4 metabolites in the gastrointestinal tract to resynthesize T4. Incubation of diiodothyronine (T2), T3, or reverse T3 with I2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with I2 to produce T4. Single oral doses of I2 to rats produced significant dose-related increases in serum T4 and decreases in T3 concentrations after 2 h. Administration of an equivalent dose of I- did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-specific antibody are present in plasma of animals treated with 125I2 compared to 125I-. These data support the hypothesis that I2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4 and elevate its levels in blood."
Distribution of iodine into blood components of the Sprague-Dawley rat differs with the chemical form administered.Thrall KD, Bull RJ, Sauer RL. J Toxicol Environ Health. 1992 Nov;37(3):443-9. [abstract only]
"It has been reported
previously that radioactivity derived from iodine distributes
differently in the Sprague-Dawley rat depending on the chemical form
administered (Thrall and Bull, 1990). In the present communication we
report the differential distribution of radioactivity derived from
iodine (I2) and iodide (I-) into blood components. Twice as much
radioiodine is in the form of I- in the plasma of animals treated with
125I- compared to 125I2-treated rats. No I2 could be detected in the
plasma. With an increase in dose, increasing amounts of radioactivity
derived from 125I2-treated animals distribute to whole blood compared
to equivalent doses of 125I-, reaching a maxima at a dose of 15.8
mumol I/kg body weight. Most of the radioactivity derived from I2
associates with serum proteins and lipids, in particular with albumin
and cholesteryl iodide. These data indicate a differential
distribution of radioactivity depending on whether it is administered
as iodide or iodine. This is inconsistent with the commonly held view
that iodine (I2) is reduced to iodide (I-) before it is absorbed
systemically from the gastrointestinal tract."
Comparison of toxicity induced by iodine and iodide in male and female rats.Sherer TT, Thrall KD, Bull RJ. J Toxicol Environ Health. 1991 Jan;32(1):89-101. [abstract only]
"In risk assessments the
various forms of iodine have been treated as if they were
toxicologically equivalent. While iodide (I-) and iodate (IO3-) have
been studied, no studies concerned with the subchronic toxicity of
iodine (I2) have been conducted in experimental animals. This study
examined toxicities associated with iodine. Rats were treated with 0,
1, 3, 10, and 100 mg/l of either iodine or iodide (as Nal) in the
drinking water for 100 d. Treatment had no effect on body, brain, or
heart weights in either sex, or on testes weights in male rats.
Although differences in kidney and liver weights were noted, they did
not appear to be treatment related. Thyroid weight in male rats was
significantly increased with an increasing concentration of iodide in
the water, but not iodine. In contrast, thyroid weight decreased at
the highest dose of iodide in female rats. Hematocrit, hemoglobin, and
blood urea nitrogen (BUN) values were relatively constant and did not
vary with treatment. There were no significant differences in AST,
ALT, cholesterol, and triglyceride values. After 10 d on treatment a
dose-related trend in increased plasma T4 concentrations was observed
in both sexes treated with iodine. Statistically significant increases
in the T4/T3 ratio in both sexes was also noted with iodine treatment.
This increase was maintained for 100 d of treatment. Iodide did not
produce this effect at 10 d. Although there was a significant increase
in T4/T3 ratios in female rats after 100 d of treatment with iodide,
the magnitude of the changes was smaller than that observed with
iodine treatments. The results of this study indicate that iodine and
iodide affect thyroid hormone status in substantially different ways."
Differences in the distribution of iodine and iodide in the Sprague-Dawley rat.Thrall KD, Bull RJ. Fundam Appl Toxicol. 1990 Jul;15(1):75-81. [abstract only]
"Use of iodine as a
drinking water disinfectant for extended space flight raises concerns
about potential chronic effects on health. A key question is whether
the chemical form of iodine might play a role. To address this
question the influence chemical form has on the uptake and
distribution of radioiodine was studied in fed and fasted rats.
Following oral administration of 125I2 or 125I-, blood 125I levels
were maximal at 2 hr and reached similar concentrations in fed animals
receiving 125I- and fasted animals receiving either 125I2 or 125I-.
However, when 125I2 was administered to fed animals the initial levels
of 125I into blood were significantly lower than after the other
treatments. The half-life of elimination of 125I from the blood
appeared independent of the form of iodine administered. The initial
distribution of 125I to the thyroid depended sharply on chemical form,
being greater when iodide rather than iodine was administered, whether
animals were fed or fasted. In fed animals administered I2, this may
largely be explained by the increased retention of 125I in the stomach
contents. In fasted animals, both stomach content and blood levels of
125I were similar whether I2 or I- was administered. Since thyroid
uptake of iodine is specific for I-, this suggests that the form of
iodine in the blood was different in animals administered I2. This
notion was further supported by the finding that pretreatment of
animals with varying concentrations of I- in drinking water was four
times as effective in suppressing the uptake of a test dose of 125I-
than pretreatment with equivalent concentrations of I2."
Formation of Organic By-Products Following Consumption of Iodine Disinfected Drinking WaterThrall KD Ph.D. Dissertation, Washington State University, Pharmacology & Toxicology, 1990.
“Not only is the distribution of radioiodine in the Sprague-Dawley rat different depending on chemical form administered, but iodinated by-products are formed in the gastrointestinal tract following oral administration of I2. Thyroxine (T4), the precursor to the active thyroid hormone, triiodothyronine (T3), is among these by-products.
“Iodine behaves differently than I- pharmacokinetically…. I2 is not quantitatively converted to I- following ingestion, as suggested in classical texts.
“There is evidence of by-product formation in the gastrointestinal tract with I2 treatment…. More specifically, I2 was shown to produce a by-product which co-migrated with cholesteryl iodide on thin layer chromatography….
“I2 treatment results in the iodination of T4 metabolites in the gastrointestinal tract to resynthesize T4….
“In subchronic studies, significant increases in thyroid size were seen in male rats treated with I-. This was not observed in animals receiving I2, where the trend was toward decreased thyroid size…. The differential effects of I2 and I- on thyroid size in the subchronic study is consistent with the present data, where I2 treatment produced an increased T4/T3 ratio and I- treatment produced a slight decrease….
“Following oral administration of radioactive I2, approximately 14% of the radioactivity in whole blood is identified as free I- by HPLC analysis. Twenty percent of the radioactivity in whole blood associates with lipids primarily in the form of a product co-migrating with cholesteryl iodide. Of the remaining 66%, a large portion (an estimated 40% of the radioactivity in whole blood) is incorporated into T4 metabolites to produce T4…. This would indicate that if I2 reacts with other materials, these reaction products are in low concentrations….
“The major criticism of iodinated drinking water is the potential for development of iodide-induced goiter in sensitive individuals. The data in the present study… indicate that I2 actually produces the reverse effect expected of I-. Therefore, prior arguments that I2 may not be a safe drinking water disinfectant appear to be unfounded. If this is true, there is a clear need to be certain that I2 is not significantly reduced to I- in finished water.”
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