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.

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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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Male and female Sprague-Dawley rats were administered 2,2,2-trichloroethanol (TCE) by gavage for 14 or 90 consecutive days. The gavage solution consisted of TCE dissolved in distilled water, containing 10% Emulphor. Doses of 37.5, 75, 150, and 300 mg/kg/day in the 14-day study and 40, 80, 160, and 320 mg/kg/day for the 90-day study were employed. Evaluation of clinical symptoms, clinical chemistry, and pathology examinations did not reveal a specific toxic effect or identify a target organ. In male rats an increase of red blood cells (RBCs) and hematocrit (Hct) in both 14- and 90-day studies, as well as increased hemoglobin (Hgb) in the 90-day study was observed at the highest dose level. In the high-dose females only increase of Hgb was seen in the 14-day study. These hematopoietic indices were not accompanied by commensurate changes in reticulocytes, mean corpuscular volumes or spleen weights. Serum lactic dehydrogenase (LDH) levels were increased in males at the two highest dose levels of both studies. Other changes in chemistries were sporadic in nature and did not appear to be dose related. Collectively, there was no basis to identify a target organ. The RBC and LDH levels did not correlate with other biochemical or pathology results and did not support the hypothesis that they represent a specific toxic effect. Based on the lack of detectable toxicity of TCE at the highest doses tested in rats, the following lowest observed adverse effect levels (LOAEL) were assigned for this chemical: in the 14-day exposure, 300 mg/kg/day for both sexes; in the 90-day protocol, 320 mg/kg/day for female; and 160 mg/kg/day for male rats.