Clinical Evaluations
Article
J R Lubbers, S Chauan, and J R Bianchine
To assess the relative safety of
chronically administered chlorine water disinfectants in man, a controlled
study was undertaken. The clinical evaluation was conducted in the three
phases common to investigational drug studies. Phase I, a rising dose
tolerance investigation, examined the acute effects of progressively
increasing single doses of chlorine disinfectants to normal healthy adult
male volunteers. Phase II considered the impact on normal subjects of
daily ingestion of the disinfectants at a concentration of 5 mg/l. for
twelve consecutive weeks.
Persons with a low level of glucose-6-phosphate dehydrogenase may be expected to be especially susceptible to oxidative stress; therefore, in Phase III, chlorite at a concentration of 5 mg/l. was administered daily for twelve consecutive weeks to a small group of potentially at-risk glucose-6-phosphate dehydrogenase-deficient subjects. Physiological impact was assessed by evaluation of a battery of qualitative and quantitative tests.
The three phases of this controlled double-blind clinical evaluation of chlorine dioxide and its potential metabolites in human male volunteer subjects were completed uneventfully. There were no obvious undesirable clinical sequellae noted by any of the participating subjects or by the observing medical team. In several cases, statistically significant trends in certain biochemical or physiological parameters were associated with treatment; however, none of these trends was judged to have physiological consequence. One cannot rule out the possibility that, over a longer treatment period, these trends might indeed achieve proportions of clinical importance. However, by the absence of detrimental physiological responses within the limits of the study, the relative safety of oral ingestion of chlorine dioxide and its metabolites, chlorite and chlorate, was demonstrated.
Abdel-Rahman MS, Couri D, Bull RJ.
Article
Since chlorination of drinking water
produces organochlorinated substances (some possibly carcinogenic), the
use of chlorine dioxide disinfectant would avoid halogenation. There is
scarcely any data published on the effects of ClO2 in drinking water on
human or animal health. The kinetics of 36ClO2 was studied in rats.
Radioactivity was rapidly absorbed from the gastrointestinal tract
following the administration of (0.07 microCi) 36ClO2 orally. 36Cl in
plasma reached at peak at 1 hr. The half life for the elimination of 36Cl
from the rat was 44 hr, corresponding to a rate constant of 0.016 hr-1.
After 72 hr radioactivity was highest in plasma, followed by kidney, lung,
stomach, duodenum, ileum, liver, spleen, thymus, and bone marrow. 36Cl
excretion was greatest at 24 and 48 hrs after the administration of 36
ClO2. Forty-three percent of the total initial dose was excreted at 72 hr
in the urine and feces. No 36 Cl was detected in expired air throughout
the 72 hr studied. ClO2, ClO2-, and ClO3- (1, 10, 100, 1000 ppm) given
daily in drinking water decreased blood glutathione, decreased osmotic
fragility, and changed the morphology of erythrocytes in both chicken and
rat after two months. Methemoglobin was not detected throughout these
studies.
PMID: 547024 [PubMed - indexed for
MEDLINE]
Article
Heffernan WP, Guion C, Bull RJ.
Sodium chlorite in drinking water was
found to produce a slight but compensated anemia in rats after exposure to
up to 500 ppm for 90 days. Decreases in hemoglobin, red cell count, and
packed cell volume seen after 30 days exposure had substantially recovered
by 90 days of treatment. Signs of adaptation remained in that
2,3-diphosphoglyceric acid concentrations in the red cell remained
elevated after 90 days exposure to 50 and 100 ppm CIO2-. However,
dose-related decreases in erythrocyte glutathione levels, detected at
chlorite levels as low as 50 ppm, remained decreased after 90 days
exposure. While no other signs of overt toxicity were observed, the fact
that hemolytic anemia was involved was confirmed by an increased turnover
of red cells in cats exposed to CIO2-. Chlorite-induced decreases in
glutathione in vivo were demonstrated to enhance formation of hydrogen
peroxide when treated further with chlorite in vitro. Consequently, before
a comprehensive determination of the hazards of chlorite in water can b:
made, particular attention must be paid to individuals sensitive to
hemolytic anemia.
PMID: 528853 [PubMed - indexed for
MEDLINE]