Chlorine dioxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Only few information on the results.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1982

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In vitro method (saliva):
Chlorine dioxide solutions were mixed with monkeys dilute saliva in a quartz cuvet and absorbance was read.
Pooled saliva was collected by buccal scraping from anaesthetized animals. The specimen was diluted 1:5 with distilled water and the resultant solution was used for the subsequent experiment. Various ratios of chlorine dioxide solutions were mixed with the dilute saliva in a quartz cuvet. The absorbance of the cuvet was read in a Perkin-Elmer u.v. spectrophotometer at 360 nm against a distilled water blank. At the same time another aliquot of the mixture was prepared and titrated according to the Palin. Recovered concentrations were calculated using the molar extinction coefficient of chlorine dioxide of 1.1E05 mole-1cm-1 and by titer equivalent.

In vivo method (gastric):
A monkey’s stomach was intubated via the oropharyngeal route and chlorine dioxide solution (60 mg/L) was instilled into the gastric space with a glass syringe. Immediately after discharging, an aliquot of the solution was withdrawn and its total oxidising capacity was determined by iodometry at pH 1.0.
A 5.7 kg male animal was lightly sedated after an overnight fast and immobilized in a monkey chair. The animal’s stomach was intubated via the oropharyngeal route and an aliquot of 30 mL chlorine dioxide solution (60 mg/L) was instilled into the gastric space with a glass syringe. Immediately after discharging, a 15 mL aliquot of the solution was withdrawn and its total oxidising capacity was determined (within five minutes) by iodometry at pH 1.0.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Chlorine dioxide

EC Number:

233-162-8

EC Name:

Chlorine dioxide

Cas Number:

10049-04-4

Molecular formula:

ClO2

IUPAC Name:

Chlorine Dioxide

Details on test material:

A stock ClO2 solution of 400-500 mg/L was prepared by purging ClO2 from an acidified NaClO2 generator through an absorbent NaClO2 solid column into 1 gallon quantities of distilled deionized water.
Description: water-soluble yellow oxidant gas
Purity: Not specified (although determined before administration and at time of refilling)

Radiolabelling:

no

Test animals

Species:

monkey

Strain:

other: African Green Monkeys (Ceropithicus aethiops)

Sex:

male

Details on test animals or test system and environmental conditions:

Age/weight at study initiation:
Age: adult
Weight: 3.0 – 5.7 kg

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration and frequency of treatment / exposure:

single administration

Doses / concentrations

Remarks:

Doses / Concentrations:
In vitro (saliva): 30 and 300 mg/L
In vivo (gastric): 60 mg/L

No. of animals per sex per dose / concentration:

1 male monkey in the in vivo study

Control animals:

other: For purposes of statistics and evaluation, each animal served as its own control.

Details on study design:

Pooled saliva was collected by buccal scraping from anaesthetized animals. The specimen was diluted 1:5 with distilled water and the resultant solution was used for the subsequent experiment. Various ratios of chlorine dioxide solutions were mixed with the dilute saliva in a quartz cuvet. The absorbance of the cuvet was read in a Perkin-Elmer u.v. spectrophotometer at 360 nm against a distilled water blank. At the same time another aliquot of the mixture was prepared and titrated according to the Palin. Recovered concentrations were calculated using the molar extinction coefficient of chlorine dioxide of 1.1E05 mole-1cm-1 and by titer equivalent.
A 5.7 kg male animal was lightly sedated after an overnight fast and immobilized in a monkey chair. The animal’s stomach was intubated via the oropharyngeal route and an aliquot of 30 mL chlorine dioxide solution (60 mg/L) was instilled into the gastric space with a glass syringe. Immediately after discharging, a 15 mL aliquot of the solution was withdrawn and its total oxidising capacity was determined (within five minutes) by iodometry at pH 1.0.

Details on dosing and sampling:

Sampling times in chlorine dioxide fate tests:
In vitro (saliva): 1 minute
In vivo (gastric): 5 minutes

Samples were as follows:
Clinical test samples:
ClO2: red cell GGPD; red cell count and indices; reticulocytes; osmotic fragility; methemoglobin content; haemoglobin content; white cell count and differential; creatine and BUN; total bilirubin; total protein, albumin; alkaline phosphatase, LDH, SGOT, SGPT, total T-4, body weight measurement
ClO2-: red cell count and indices; reticulocytes; osmotic fragility; methemoglobin content; haemoglobin content; white cell count and differential; red cell GHS content; creatine and BUN; total bilirubin; total protein, albumin; alkaline phosphatase, LDH, SGOT, SGPT, total T-4, body weight measurement.
Chlorine dioxide fate tests:
In vitro (saliva): Percentage recovery of chlorine dioxide
In vivo (gastric): Total oxidizing capacity

Results and discussion

Preliminary studies:

Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not applicable

Details on distribution in tissues:

not applicable

Details on excretion:

not applicable

Toxicokinetic parameters

Toxicokinetic parameters:

other: In the in vivo study 8% of the original ClO2 equivalent oxidizing titer was recovered after 5 min of total contact time.

Metabolite characterisation studies

Metabolites identified:

not specified

Any other information on results incl. tables

Table 7.1.1/1: In vitro inactivation of ClO₂ in saliva after 1 min reaction time

 

Ratio Saliva: ClO2	Concentration of ClO2 (mg/L)	Percentage of recovery measured by:
		Spectral	Titration
1:9	300	39	46
		26	28
1:1	30	12	11
		5	4

 

Applicant's summary and conclusion

Conclusions:

Chlorine dioxide is rapidly reduced by saliva and gastric juices to non-oxidizing species (most likely chloride).

Executive summary:

In an in vivo study, the male African Green Monkey's stomach was intubated via the oropharyngeal route and an aliquot of 30 mL chlorine dioxide solution (60 mg/L) was instilled into the gastric space with a glass syringe. Immediately after discharging, a 15 mL aliquot of the solution was withdrawn and its total oxidising capacity was determined (within five minutes) by iodometry at pH 1.0.

Of the original ClO2 equivalent oxidizing titer, 8% was recovered after 5 min of total contact time.

In an in vitro study, pooled saliva was collected by buccal scraping from anaesthetized African Green Monkey. The specimen was diluted 1:5 with distilled water and the resultant solution was used for the subsequent experiment. Various ratios of chlorine dioxide solutions were mixed with the dilute saliva in a quartz cuvet. The absorbance of the cuvet was read in a Perkin-Elmer u.v. spectrophotometer at 360 nm against a distilled water blank. At the same time another aliquot of the mixture was prepared and titrated according to the Palin. Recovered concentrations were calculated using the molar extinction coefficient of chlorine dioxide of 1.1E05 mole-1cm-1 and by titer equivalent.

In conclusion, Chlorine dioxide is rapidly reduced by saliva and gastric juices to non-oxidizing species (most likely chloride).