Subchronic toxicity of chlorine dioxide and related compounds in drinking water in the nonhuman primate.

Abstract

Subchronic toxicities of C1O2, NaCIO2, NaCIO3 and NH2CI were studied in the African Green monkeys (Cercopithecus aethiops). The chemicals were administered in drinking water during 30-60 days subchronic rising dose protocols. The only unexpected and significant toxic effect was elicited by C102; this chemical inhibited thyroid metabolism in the animals at a dose of ca. 9.0 mg/kg/day. A statistically significant decrease of serum thyroxine occurred after the fourth week of exposure to 100 mg/l.concentration. The extent of thyroid suppression was dose dependent in each individual monkey, and was reversible after cessation of exposure. NaCIO2 and NaCIO3 failed to elicit similar effects in doses up to ca. 60 mg/kg/day. Also, NaCIO4 or NH2CI did not cause TA suppression in doses of 10 mg/kg/day. The selective thyroid effect of C102 was unexplained and it appeared to be paradoxical since C102 was rapidly reduced by the oral and gastric secretions to nonoxidizing species (presumably Cl-). No evidence of thyroid effects were detected in the serum of human volunteers who ingested -1 mg/I. of C102 in drinking water as a result of routine use in the community water treatment process.Sodium chlorite induced dose-dependent oxidative stress on hematopoesis, causing decreased hemoglobin and red cell count and increased methemoglobin content. At the same time, serum transaminase (SGPT) levels showed significant subclinical elevation. The hematologic effects of NaCl02 rebounded during exposure indicating compensatory hemopoietic activity taking effect during oxidative stress. Sodium chlorate and chloramine did not induce detectable hematologic changes in the animals.

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

“…Bercz et al (4) reported that exposure of monkeys to ClO 2 , but not ClO 3 , resulted in decreased serum T 4 levels. 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 .…”

“…In addition, some data suggest that perchlorate causes a release of accumulated iodide from the gland (3,41). Similarities in thyroid histopathology between perchlorate and chlorate exposure suggest that chlorate may interfere with iodide uptake as well, resulting in stimulation of thyroid follicular cell proliferation mediated by TSH secondary to decreases in T 3 and T 4 . This hypothesis needs to be investigated to determine if the mechanism of chlorate-induced thyroid follicular cell hyperplasia is indeed the same as perchlorate.…”

“…Other subchronic toxicity tests have identi ed the rat thyroid as the primary target organ. Bercz et al (4) reported a concentration-dependent decrease in thyroxine (T 4 ) levels in African green monkeys exposed to ClO 2 in drinking water. A statistically signi cant decrease in T 4 levels occurred after 4 weeks of exposure to 0.1 g/L (9 mg/kg/day) ClO 2 , but changes in T 4 levels did not occur when the animals were exposed to 0.4 g/L (60 mg/kg/day) of NaClO 3 .…”

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

“…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. A significant frequency distribution shift to the smaller follicle categories suggests an increase in the activity of the thyroid gland and/or multiplication of smaller and probably more active follicles.…”

Excessive iodine intake, water chemicals and endemic goitre in a Sudanese coastal area

“…It has been reported that chlorine and some other chemicals can form different products when they react with organic matter in the upper gastrointestinal tract. These products exert significant antithyroidal effects (11,12) . Several environmental chemicals have structural similarities to the thyroid hormones thyroxine (T 4 ) and triiodothyronine (T 3 ).…”