Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles in processes that are different from pathogen killing, as signal transduction, differentiation, ...

****!!!!**** " Hemolysis and renal dysfunction have been reported at concentrations of 40 ppm. The patients,came to control their eye problems, but the findings differed significantly from those found before the intake of chlorine dioxide." "slowly absorbed through shaved skin with a half absorption time of 22 h." " more likely that its derivatives can be absorbed [3]. Chlorine dioxide is metabolized to chlorite (ClO2), chlorate (ClO3), and mostly chloride (Cl). Most administered chlorine dioxide and its metabolites remain in plasma followed by kidneys, lungs, stomach, intestine, liver, and spleen. About 43% of orally administered chlorine dioxide is eliminated in the urine and feces within 72 h. It is not excreted via the lungs."

**** (2021) "The man presented to the hospital with complaints of generalised bruising on the extremities, chest and back with no external bleeding. Additionally, he had back and thigh pain, anorexia and asthenia. It was reported that he had been drinking chlorine dioxide (20−30 ppm) solution daily for a month for the prevention of COVID-19"

"Chlorine dioxide concentration =or 0.44% w/w" "Environmental hazards: Not currently regulated by OSHA, refer to Section 12 for additional information." "OSHA defined hazards: While this material is not considered hazardous by the OSHA Hazard Communication Standard (29 CFR 1910.1200), the SDS contains valuable information critical to the safe handling and proper use of the product. The SDS should be retained and available for employees and other users of this product. " "There are no additional ingredients present which, within the current knowledge of the supplier and in the concentrations applicable, are classified as hazardous to health and hence require reporting in this section. "

We present a case report of a 41-year-old woman of Malay ethnicity who presented with an 11-day history of fever and left-sided lymphadenopathy after consuming ‘Miracle Mineral Solution’ (sodium chlorite solution) for the first time.

"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."

*****

"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. "

*****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

{Data resources on chemical safety, including from EPA}

Read chapter Appendix 1 Chlorine Dioxide Acute Exposure Guideline Levels (AEGLs): Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume ...

Data on Acute Exposure Guideline Levels (AEGLs). Chlorine Dioxide Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 5, 2007.

The use of electrophysiological and molecular biology techniques has shed light on reactive oxygen species (ROS)-induced impairment of surface and internal membranes that control cellular signaling...

****!!!!*** "Previous investigators have reported cardiovascular abnormalities in experimental animals exposed to chlorinated water. Plasma thyroxine (T4) levels were significantly decreased in pigeons fed a normal or high-cholesterol diet and drinking water containing these drinking water disinfectants at a concentration of 15 ppm for 3 months" "The factor(s) associated with the effect of these disinfectants on plasma T4 and cholesterol is not known. We suggest however that these effects are probably mediated by products formed when these disinfectants react with organic matter in the upper gastrointestinal tract."

****!!!**** 1982 "The primary products resulting from ClO2 disinfection of waters are chlorites (ClO2-) and chlorates (ClO3-). Studies in rats revealed that ClO2 is converted to chloride (Cl-), ClO2- and ClO3-. ClO2- and ClO3- are excreted as Cl-, ClO2- and Cl-, ClO2-, ClO3-, respectively. Radioactivity was rapidly absorbed from the gastrointestinal tract following the administration of 36ClO2 orally, and the half-life for the elimination of 36Cl from the rat was 44 hr, corresponding to a rate constant of 0.016/hr. After 72 hr, radioactivity was highest in plasma, followed by kidney, lung, and stomach. 36Cl in plasma reached a peak at 2 hr and 1 hr after oral administration of 36ClO2- and 36ClO3-, respectively. 36Cl excretion was greatest 24 hr after the administration of 36ClO3-, but in the case of 36ClO2-, the excretion probably represented saturation of the biotransformation and excretion pathway. A low activity in packed cells compared to plasma was detected in chlorate ingestion, rather than an even distribution in chlorite treatment. Chloroform determinations in rat blood after one year indicated that chloroform was significantly higher than control in the 100 and 1000 mg/l. ClO2 groups. However, no significant values were observed in the 1 or 10 mg/l. ClO2 and ClO2 metabolites groups. ClO2 and its metabolites are eliminated from the body more rapidly than chlorine, and they do not appear to increase trihalomethane concentrations at low dosages."

*****!!!**** 1979. "Studies in the rat indicated that the metabolites of ClO2 were Cl-, ClO-2, and ClO-b. At maximum absorption the percentage of ClO; formed in plasma from an initial oral dose of 10 mg/l 36ClO, was higher than from a 100 mg/l dose. The 36Cl concentration in washed packed cells indicated that 36Cl readily exchanges with chloride of saline."

1982. *******!!!!!!!!****** "In drinking water has demonstrated alterations in hematologic parameters in all species tested. The effects were usually dose related and marked changes occurred only at the higher dosages (up to 1000 mg/l.)." "Treatment groups receiving ClO2, ClO2- or ClO3- showed alterations in erythrocyte morphology and osmotic fragility; at higher dosages mild hemolytic anemia occurred. An examination of blood glutathione content and RBC enzymes involving glutathione formation showed a dose-related diminution of glutathione in chlorine compound treated groups. The higher oxidative capacity of the chlorine compounds resulting in the decreased erythrocytic glutathione might well be the principal biochemical event leading to the other hematological alterations. More recent data show that ClO2, ClO2- and ClO3- alter the incorporation of 3H-thymidine into the nuclei of various organs of the rat. These data suggest the possibility of increased turnover cells of the gastrointestinal mucosa and inhibited DNA synthesis in several organs. In the latter category, most concern revolves around whether or not the apparent depression of DNA synthesis in the testes is associated with depressed spermatogenesis and reproductive toxicity in the male rat."

****!!!** "Sodium hypochlorite and sodium chlorite are commonly used as disinfectants, and understanding the mechanisms of microbial resistance to these compounds is of considerable importance. In this study, the role of oxidative stress and antioxidant enzymes in the sensitivity of the yeast Saccharomyces cerevisiae to hypochlorite and chlorite was studied. Yeast mutants lacking Cu-Zn superoxide dismutase, but not mutants deficient in cytoplasmic and peroxisomal catalase, were hypersensitive to the action of both hypochlorite and chlorite. Both compounds depleted cellular glutathione, induced the production of reactive oxygen species and decreased the viability of the cells. The toxicity of hypochlorite and chlorite was abolished by hypoxic and anoxic conditions and ameliorated by thiol antioxidants and ascorbate. The results demonstrated that the action of hypochlorite and chlorite involves the formation of superoxide and peroxide and that SOD1 is protective, probably by limiting the formation of hydroxyl radicals and damage to proteins. "

Oxoferin, a preparation approved for wound treatment, has been subjected to an in vitro analysis. 1. Oxoferin produces methaemoglobin even if diluted 500 fold, and leads to additional alterations if added in high concentrations to red cells. Sodium chlorite (NaClO2, 15 mM) is equivalent to undiluted …

Chlorine dioxide oxidation of cysteine (CSH) is investigated under pseudo-first-order conditions (with excess CSH) in buffered aqueous solutions, p[H+] 2.7−9.5 at 25.0 °C. The rates of chlorine dioxide decay are first order in both ClO2 and CSH concentrations and increase rapidly as the pH increases. The proposed mechanism is an electron transfer from CS- to ClO2 (1.03 × 108 M-1 s-1) with a subsequent rapid reaction of the CS• radical and a second ClO2 to form a cysteinyl−ClO2 adduct (CSOClO). This highly reactive adduct decays via two pathways. In acidic solutions, it hydrolyzes to give CS...

**********{Repeated Dose Oral Toxicity study on mice}

*****{Many evaluations of effects on body} "It is assumed that chlorine dioxide as such is not absorbed by oral since it rapidly reacts with saliva and gastric juices. Furthermore, the total recovered in urine after dermal administration indicates that dermal absorption is poor. These findings were consistent regarding the reactive properties of the dioxide chlorine. ClO2 was reduced rapidly after an oral administration in Chloride (Cl-), Chlorite (ClO2-) and Chlorate (ClO3-) ions. Seventy-two hours after a single gavage dose of 100 mg/L 36ClO2, most of the 36Cl label in the plasma was in the form of chloride ion (Cl-) and chlorite; the ratio of chloride to chlorite was 4 to 1. Chloride ion is the ultimate metabolite of chlorine dioxide. Seventy-two hours after 36ClO2 oral dosing, 31% and 10% of the radioactivity were measured in the urine and the faeces, respectively while radioactivity was not detected in the expired air. The parent compound was not detected in the urine; most of the radioactivity was in the form of chloride, with smaller amounts as chlorite. Chlorine dioxide skin contact resulted in a reduction of ClO2 to chlorite followed by reduction to chloride. Therefore, it is assumed that chlorine dioxide is not absorbed at significant rate after skin contact.

LD50 labels for Categories 1-5

2008. The bactericidal, fungicidal and virucidal activity of chlorine dioxide (CIO2) against 79 bacteria, 31 yeasts and 4 viruses were evaluated under clean and dirty conditions. The safety of CIO2 to chickens given by drinking water or skin spraying was also evaluated. In clean diluent condition, the median lethal concentration (MLC50) of CIO2 against bacteria and yeast was 9.4 and 8.4 ppm, respectively. In dirty diluent condition, the MLC50 of CIO2 against bacteria and yeasts was 39.9 and 24.3 ppm, respectively. The virucidal activity of CIO2 against 100 median embryo lethal dose (100 ELD50) of Newcastle disease virus, avian influenza virus, infectious bronchitis virus and infectious bursal disease virus was 1.2, 1.2, 2.5 and 1.2 ppm, respectively. All the leghorn chickens continuously given with 10 mL of 500, 250, 125, 62.5 or 0 ppm of CIO2 in drinking water or on skin spraying for 7 days were not found showing any abnormality at 14 days post medication. Chlorine dioxide provides high bactericidal and virucidal activity without resulting any toxicity to the chickens.