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Description of key information

Short description of key information on bioaccumulation potential result:

A weight of evidence approach was used to assess the toxicokinetic behaviour of Chlorine dioxide.

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.

Short description of key information on absorption rate:

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.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

It is assumed that chlorine dioxide as such is not absorbed after oral administration 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 Chlorine dioxide. In fact, ClO2 was rapidly reduced after an oral administration in Chloride (Cl-), Chlorite (ClO2-) and Chlorate (ClO3-) ions.

In the same way, skin contact resulted in a reduction of ClO2 to chlorite followed by a reduction to chloride.

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 and chlorite; the ratio of chloride to chlorite was 4 to 1. Chloride ion is the ultimate metabolite of chlorine dioxide.

In the same experiment, 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.

Discussion on bioaccumulation potential result:

In a series of experiments considered as weight of evidence, radiolabelled Chlorine Dioxide (36ClO2) or Chlorite (36ClO2-) were administered to rats by oral or dermal route resulting to the following discussion:

Absorption: After ingestion, chlorine dioxide is rapidly absorbed from the gastrointestinal tract. Levels of 36Cl in plasma peaked 1 hour after Sprague-Dawley rats were administered a single gavage dose of 100 mg/L 36ClO2 (approximately 1.4 mg/kg) (Abdel-Rahman, 1980b). Peak plasma levels were achieved 2 hours after Sprague-Dawley rats received a gavage dose of 300 mg/L 36ClO2 after a 15-day exposure to 100 mg/L chlorine dioxide in drinking water (Abdel-Rahman, 1980b). Approximately 30% of the 100 mg/L single gavage dose was excreted in the urine after 72 hours, indicating that at least 30% of the dose was absorbed (Abdel-Rahman, 1980b); the absorption rate constant and half time were 3.77/hour and 0.18 hours, respectively (Abdel-Rahman, 1982).

There are good reasons to assume that chlorine dioxide as such is not absorbed since it rapidly reacts with saliva and gastric juices (Bercz, 1982). Furthermore, the total recovered in urine after dermal administration indicates that dermal absorption is poor (Scatina, 1984).

Distribution: Following a single 100 mg/L gavage dose of 36ClO2, the 36Cl was slowly cleared from the blood; the rate constant and half-time for elimination from blood were 0.0156/hour and 43.9 hours, respectively (Abdel-Rahman, 1982). Elimination from blood was shortened in Sprague-Dawley rats exposed to chlorine dioxide in drinking water for 2 weeks prior to receiving the 300 mg/L gavage dose of 36ClO2; the rate constant and half time were 0.022/hour and 31.0 hours, respectively (Abdel-Rahman, 1980b). After removal from the blood, the radiolabel appeared to be widely distributed throughout the body, although the highest concentrations were found in the blood, stomach, and small intestines. The lung, kidney, liver, testes (assessed only in the 300 mg/L group), spleen, thymus, and bone marrow also had high concentrations of radiolabel 72 hours after dosing with 100 mg/L (single dose) or 300 mg/L (with 2-week drinking water exposure to 100 mg/L) (Abdel-Rahman, 1980b). 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 (Abdel-Rahman et al., 1980a).

Metabolism: ClO2 was reduced rapidly after an oral administration in Chloride (Cl-), Chlorite (ClO2-) and Chlorate (ClO3-) ions (Abdel-Rahman 1980a and 1982). Chloride ion is the ultimate metabolite of chlorine dioxide.

Chloride was the major metabolite: 72 hours after the administration of 100 mg/L ClO2, approximately 27% of Cl- was found in the urine, whereas this percentage was approximately 3,5% for ClO2- and lower than 1% for ClO3- (Abdel-Rahman, 1982). At 72 hours following administration, chloride ion accounted for approximately 87% of the radioactivity that had been collected in the urine and 80% of the radioactivity in a plasma sample. Chlorite was the other major metabolite, accounting for approximately 11 and 21% of the radioactivity in the urine and plasma samples, respectively. Chlorate was a minor component of the radioactivity in the urine (Abdel-Rhaman, 1980a).

In conclusion, very little chlorine dioxide is converted to chlorate, so that the major pathway of breakdown is reduction to chlorite and chloride and the pathway forming chloride from chlorite is saturable.

Excretion: The radioactive chlorine label was primarily excreted in the urine of rats administered a single gavage dose of 100 mg/L 36ClO2 (Abdel-Rahman et al., 1980b). During the first 24 hours after dosing, 18% of the label was excreted in the urine and 4.5% in the faeces. Seventy-two hours after dosing, 31% and 10% of the label were excreted in the urine and faeces, respectively; the label was not detected in expired air. The parent compound was not detected in the urine; most of the label was in the form of chloride, with smaller amounts as chlorite. The ratio of 36Cl-

to 36ClO2 was 5 to 1 during the first 24 hours and 4 to 1 during the first 72 hours (Abdel-Rahman, 1980a). 

Discussion on absorption rate:

Female Sprague-Dawley rats were exposed dermally to Alcide gel, which is a preparation composed of sodium chlorite and lactic acid in equivalent proportion. Chlorine dioxide (ClO2) is formed immediately after mixing. Authors (Scatina et al., 1984; see § 7.1.1) considered that animals are immediately exposed to chlorine dioxide when the gel is applied on the back of the animal. Animals were exposed for 10 days at the dose of 2000 mg/kg of chlorine dioxide. On the 11th day the animals which had been fasted for 24 hours received 36Cl-labelled Alcide gel. To prevent oral ingestion of the radioactive compound, animals' backs were covered with a plastic wrap securely taped to the rat. Following several times after the application of the gel, blood samples, tissues, urine, faeces and expired air were collected for analysis and quantification of 36Cl compounds.

Topical application of Alcide gel resulted in a slow rate of absorption of 36Cl labelled compounds with a half-life of 22.1 h. Both ClO2 and ClO2- are water soluble and slightly lipophilic, which could account for the decreased rate of absorption compared to the rate of absorption after an oral administration. The half-life for elimination from plasma was 64 h. This half-life was longer than that of ClO2 alone (43.9 hr) administered orally (see § 7.1.1). It is possible that contact of Alcide gel with skin resulted in a reduction of ClO2 and ClO2- to Cl-. The 36Cl labelled compounds were excreted in the urine, with chloride and chlorite as the metabolites.