“... oral ingestion by monkeys, chlorine dioxide was rapidly converted into chloride ion and, to a lesser extent, chlorite and chlorate.. In rats, excretion of chloride and, to a lesser extent, chlorite ion is mainly via the urine, smaller amounts being excreted in faeces... At typical low drinking-water levels, chlorine dioxide would be decomposed by oxidation–reduction reactions with saliva and stomach contents...” “Drinking-water containing chlorine dioxide at a concentration of 0, 10 or 100 mg/L (equivalent to approximately 0, 1.5 and 15 mg/kg bw per day) was administered to mice... with no apparent effects on blood parameters... “ “study with Sprague-Dawley rats at drinking-water concentrations ranging from 0 to 200 mg/L...enzymatic changes suggested liver toxicity; the principal effect was histopathology of nasal turbinates from inhalation of the gas. Although chlorine dioxide is water soluble, it is a gas at room temperature, so there can be difficulty in interpreting toxicity findings.” “In a 2-year study in rats at drinking-water concentrations up to 100 mg/L, the NOAEL was 10 mg/L (1.3 mg/kg bw per day)” "Currently, there is no readily available and low-cost treatment available to remove chlorate ion once it has been formed in drinking-water. "

{Provides extensive details} "Chlorine dioxide irritates the nose, throat, trachea and bronchi at very low concentrations (less than 5 ppm) resulting in breathlessness, wheezing and coughing. Higher concentrations can cause inflammation in the upper respiratory tract, bronchial spasms and difficulty in breathing. A potentially fatal accumulation of fluid in the lungs (pulmonary edema) could occur. Symptoms of pulmonary edema (chest pain and shortness of breath) can be delayed for up to 24 or 48 hours after exposure. Long-term respiratory effects (e.g. sensitivity to respiratory irritants, chronic nasal inflammation, asthma, pulmonary emphysema and spastic bronchitis) have been noted in workers accidentally exposed to unspecified concentrations for a short time"

****!!!!*** "Devices, compositions, systems and methods for the non-cytotoxic delivery of chlorine dioxide to a tissue." "Cytotoxicity of chlorine dioxide-containing compositions results predominantly from the presence of oxy-chlorine anions, and not from the presence of chlorine, which can be a product of chlorine dioxide decomposition." " mucosal tissue, epidermal tissue, dermal tissue, and subcutaneous tissue (also called hypodermis tissue). Mucosal tissue includes buccal mucosa, other oral cavity mucosa (e.g., soft palate mucosa, floor of mouth mucosa and mucosa under the tongue), vaginal mucosa and anal mucosa... Biological tissue may be intact or may have one or more incisions, lacerations or other tissue-penetrating opening.” "tooth enamel, dentin, fingernails, toe nails, hard keratinized tissues and the like, found in animals" "In some embodiments, the method is practiced on a chronic wound of soft tissue"

"This study was carried out in order to assess the effects of disinfectant-treatment on antioxidant response of Cyprinus carpio L. Therefore, enzymatic activities of glutathione S-transferases, glyoxalase I, glyoxalase II, glutathione peroxidases, glutathione reductase, catalase and total glutathione content of carp liver, exposed to surface water treated with three disinfectants for potabilization, sodium hypochlorite, chlorine dioxide and peracetic acid were investigated. " "[Need to verify whether this included effects of chlorine dioxide] chlorine compounds induced marked biochemical variations of carp liver"

"A single-dose oral toxicity study in rats... LD50 was calculated to be 290mg/kg" ".LD50 for intravenous administration was calculated to be 33.3 mg/kg" "LD50 for intraperitoneal administration was calculated to be 87.7 mg/kg" "A single dose acute dermal toxicity study in rats was conducted by exposing shaved skin...none of the animals showed any signs of systemic toxic effect or local irritation. The author concluded that the LD50 for dermal application is higher than 50 mg/kg."

****!!!****!!!!!*** 2001 {Tests on rats} "The acute toxicity and build-up toxicity of mice were tested by Horn's method and accumulation coefficient method, and the acute toxicity and accumulation toxicity of mice were studied through 90-day feeding tests on rats Subchronic toxicity of ClO2 and its by-products ClO-2 and ClO-3 mixed aqueous solutions, including weight gain, food utilization, hematological indicators, serum biochemical indicators, statistical analysis of liver (kidney) /weight ratio variance, and pathological histology microscopy of liver (kidney). The results showed that the ClO2 aqueous solution of 2 76.5mg/l, the NaClO2 and NaClO3 aqueous solution of 2 0 mg/l and the mixed aqueous solution with a total concentration of 553mg/lClO2 were all actual non-toxic aqueous solutions. 2 76.5mg/l ClO2, 2 0 0mg/l NaClO2 and NaClO3 aqueous solutions are also aqueous solutions without significant build-up; ClO2 mixture had no significant effect on weight gain and food utilization in rats (p 0 .0 5); There was no effect on rat hematological indicators such as white blood cell count (WBC) and hemoglobin (Hb) (p 0 .0 5); Tests of glutat-propylene transaminase (ALT), total protein (TP), albumin (ALB) and globulin (GLO) showed no significant difference between the control group and the high-dose group (p 0 .0 5); The liver-to-body ratio (%) and renal ratio (%) of rats in each test group and control group were analyzed by variance, and there was no significant difference between the groups (p 0 .0 5); Pathological histological examination results showed that no lesions were seen in the liver and kidney tissues of the test groups and control groups."

**** "These observations are of much clinical significance in view of the retention of these products' active agent, i.e. 90 %) may effectively exert its essential microbicidal, anti-periodontal and oral malodour-neutralising actions."

(Citing separate studies...) "This neutralizing property of ClO2, combined with its ability to completely disinfect, makes DIOXIDERM and DIOXIGUARD ideal wound medications. Unlike iodine compounds, healing is not impeded. Veterinarians have been treating deep wounds and abscesses on tigers and elephants as well as dogs and cats with outstanding success. DIOXIDERM GEL had similar striking results on human (otherwise non-healing) diabetic ulcers." "Rats and honeybees were fed ClO2 in high doses over a two year period. No ill effects were noted" " With prolonged feeding toxicity is produced mainly in the red blood cell. Rats fed up to 1000 mg/l chronically for 6 months showed no significant hematological changes. After 9 months, however, red blood cell counts, hematacrit and hemoglobin were decreased in all treatment groups. " "At high ClO2 ppm, the method of rapid bacterial and viral kill appears to be the softening and destroying of the cell wall or viral envelope.53 Human cells do not have cell walls and are apparently unaffected. Our skin and bodies are likely protected from the general oxidative effects of ClO2 by the many reducing agents in our cells and blood such as catalase, glutathione, superoxide dismutase, vitamins E, C, A, B complex, uric acid, zinc and selenium. " "100 ppm 70,71,72, about the concentration of Frontier's DioxiDerm gel for topical us"

{Includes references to CD exams by various agencies} Following a request from the European Commission, the risks to human health related to the presence of chlorate in food were assessed by the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel...

1978. {Note: Sodium chlorate is one small byproduct of chlorine dioxide water treatment, in various quantities depending on conditions} "...associated with a high mortality rate, death occurring from massive intravascular haemolysis and acute renal failure. We report the outcome in 14 patients poisoned by socium chlorate, with special regard to the amount ingested."

{includes safety limits for Chlorine Dioxide}

***** 1998. "Despite the advantages of chlorine dioxide as an adjunct to free or combined chlorine, water suppliers, consultants, and academic and regulatory professionals continue to express concern about its potential health effects. This article discusses the major health effects of chlorine dioxide and offers practical ways to reduce the potential risks associated with its use."

"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"

"Chlorine dioxide treatment even at 400 ppm for 6 h did not kill any T. castaneum. However, the combined treatment of chlorine dioxide with the heat treatment for 6 h resulted in 95% mortality. These results indicated that heat treatment suppressed the evasive behavior of T. castaneum and synergized the control efficacy of the chlorine dioxide fumigant. "

2002

**"SKIN: 12% sodium chloritewas applied to intact or abraded guinea pig skin as a 5% or 10% aqueous solution." "AIR: Vapors from the 6% solution were lethal to 1 rabbit and to 1 of 2 rats exposed for 1 hour. The rabbit's **eyes** showed superficial corneal damage. Death was due to pulmonary congestionand edema. The 3% solution did not cause anydeaths, butpr ducedthe same clinical signs and pathology as the 6% solution... The concentrations of chlorine dioxide in the chamber were not measured. In the second acute inhalation study, chlorine dioxide was generated by adding a sodium chlorite (CAS#7758-19-2) solution drop wise at a constant rate into a heated flask containing 85% phosphoric acid..." "Exposureto an average concentration of 54 ppm for I hour or 38 ppm for 4.5 to 6 hours was lethal in all cases to exposed rats (highly toxic). The clinicalsigns were cyanosis, dyspnea, salivation, lacrimation and chromodacryorrhea. Death was due to pulmonary congestionand edema. An average concentration of 26ppm for 6 hours was not lethal. No pathology was found in the rats sacrificed at 24 hours or 10 days after exposure"

[Old - 1984?] Isopropyl alcohol is manufactured in the United States by an indirect hydration technique in which a fraction containing 40-60% propylene that is isolated from refinery exhaust gases reacts with sulfuric acid (Lowenheim and Moran, 1975). In an older (strong-acid) process, 88-93% sulfuric acid reacted with propylene gas at 25-60°C for a long time. In a newer (weak-acid) process, which has replaced the strong-acid process, propylene gas is absorbed in 60% sulfuric acid at 85°C for a short reaction time (NIOSH, 1976). Estimated annual production capacity for 1981 was 2.8 million pounds (SRI, I...

"Subchronic toxicity of the mixture of ClO2, ClO2- and ClO3- in water on rat was studied through feeding test for 90 days. Statistical analyses of variance on weight gained, food utilization efficiency, indexes of blood and serum, liver/bodyweight and kidney/bodyweight ratios, and histopathological examination on liver and kidney were carried out. The results showed that solution of ClO2 and its by-products ClO2- and ClO3- at a concentration of 553 mg/L was not toxic."

***"Since ClO2 disproportionates to form ClO2- and ClO3- in alkaline solutions and decomposes to yield ClO3- in acidic solutions with exposure to sunlight..." "Toxicological effects... were first associated with the hematopoietic system. .. ClO2- produced anemia at lower exposure levels than those required to produce significant increases in methemoglobin. The anemia was associated with oxidative damage to the red blood cell membrane." "Hematological effects were observed in monkeys with ClO2- and ClO3- but not with ClO2. Monkeys exposed to ClO2 displayed dose-related decreases in serum thyroxine levels. The hypothyroid effect was unique to ClO2..." "CI02 exposure to developing rats delayed brain development and behavior" "Recent experimental findings sugest that ClO2 but not ClO2- might increase cardiovascular disease risk by increasing plasma cholesterol levels and increasing the size of plaques in blood vessels of pigeons that had received a diet high in lipid and marginal in calcium..." ""In evaluating the health impacts of ClO2, the potential of in vivo ***formation of iodinated organics from iodine present in body fluids (saliva and gastric juices) should be of concern."

"Chlorination products measured at the clinic after this purification and prior to preparation of the dialysate consisted only of chlorite at the 0.02-0.08 mg/L level. No evidence of CIO2-induced anemia was found, nor were any other biologically significant responses observed. Study limitations include several potentially important hematologic parameters which were not measured"

"In a previous study from this laboratory, chlorine dioxide (ClO 2 ) treated drinking water depressed thyroxine (T 4 ) levels in the African green monkey. The present study again demonstrated a decrease in T 4 levels in the same species after 4 wk of oral exposure. However, after 8 wk of treatment T 4 levels rebounded to above pretreatment levels, coinciding with an increase in thyroid radioiodide uptake. This T 4 rebound phenomenon and increased iodide uptake may be due to a compensatory endocrinological mechanism. In rats, T 4 levels dropped during the 8‐wk ClO 2 treatment period in a dose‐dependent manner, and no rebound effect was observed. Iodide uptake values in the rat were not affected. It appears that ClO 2 may have an effect on thyroid function in both species."

*****Toxicity Category I. 0.5 gram of sodium chlorite powder applied 4 hours --Beginning 5 hours post-dose, rabbits had severe dermal irritation and eschar formation, irreversible 14 days post-dose.

****Results: Deaths and severe skin damage