Administrative data

Purpose flag:
weight of evidence
Study result type:
experimental result
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
The study is performed similarly to the OECD guideline No. 417, but it is not a GLP study, and only the metabolism of chlorine dioxide is studied.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
: only male rats are tested, no information on the toxicity of the treatment
Methods:
in vivo
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
Study performed before GLP establishment
Objective of study
Objective of study:
metabolism

Test materials

Identity of test material same as for substance defined in section 1 (if not read-across):
yes
Test material identityopen allclose all
Details on test material:
- Name of test material (as cited in study report): chlorine Dioxide
- Specific activity (if radiolabelling): 0.7 µCi
- Physical state: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: assumed to be stable during the test (sponsor responsibility)
- Storage condition of test material: no data
- Other: The generation of 36ClO2 from K36ClO3 was accomplished by the following reaction: 2K36ClO3 + (COOH)2 + 2H2SO4  236ClO2 + 2KHSO4 + 2CO2 + 2H2O. The 36ClO2 gas was trapped in ice cold water.
Radiolabelling:
yes
Remarks:
36Cl

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
Weight at study initiation: 180 - 200 g.
Animals were housed in metabolism cages.
no other information

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
no data
Details on exposure:
no details
Duration and frequency of treatment / exposure:
single administration
Doses / concentrations:
10 and 100 mg/L
No. of animals per sex per dose:
4 animals/group
Control animals:
no data
Positive control:
no
Details on study design:
no details
Details on dosing and sampling:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine and plasma
- Time and frequency of sampling: Urine was collected at 12, 24, 48 and 72 h, Blood was collected at 72 h at termination. In another experiment, some animals were killed after ½ hr post dose for plasma analysis
- From how many animals: (samples pooled or not): 4
- Method type(s) for identification: The radioactivity was determined in a packard Model 3255 liquid-Scintillation spectrometer. Sample quench effects were corrected by using the method of channel ratios
- Limits of detection and quantification: no data
- Other:
Statistics:
no data

Results and discussion

Preliminary studies:
Not applicable

Pharmacokinetic studies

Details on absorption:
Not applicable
Details on distribution in tissues:
Not applicable
Details on excretion:
Not applicable

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Metabolites of chlorine dioxide were identified as chloride (Cl-), chlorite (ClO2-) and chlorate (ClO3-) ions. Chloride was the major metabolite: 72 hrs 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-metabolites (Abdel-Rahman, 1982). In proportion of all the metabolites of chlorine dioxide, chloride ions at 72 hours accounted for approximately 87% of the radioactivity that had been collected in the urine and 79% of the radioactivity in a plasma sample, whereas chlorite accounted for approximately 11 and 21 % of the radioactivity in the urine and plasma samples, respectively and to a lesser extent chlorate accounted for approximately 2.3%.

Bioaccessibility

Any other information on results incl. tables:
Quantitation of 36Cl Compounds in biological fluids:
When ClO2- in H2O was tested, 7.1%, 21.46% and 53.87 % ClO3-, Cl- and ClO2-were recovered respectively.
Metabolism of ClO2 in rat:
Rat urine was collected at 12, 24, 48 and 72 h after an oral administration of 100 mg /36ClO2.  Percentages of 6.09 ± 4.7, 8.06 ± 1.82, 12.33 ± 7.99, 0.46 ± 0.13 were detected as the Cl-form at 12, 24, 48 and 72 h respectively.  For the same time periods ClO2- values were 1.22 ± 0.82, 1.63 ± 0.64, 0.48 ± 0.48, 0.13 ± 001, while ClO3-was 0.73 ± 0.73 at 24 h only.  At 72 h, Cl- and ClO2- in plasma were 0.82 ± 0.11, 0.22 ± 0.07, respectively as percentage the initial dose in 1 mL. 
Table 7.1.1/1: Metabolism of ClO2 in rat
Sample analysed
Collection period (hrs)
% of Analyte
Cl-
ClO2-
ClO3-
Urine
0-12
6.09 ± 4.70
1.22 ± 0.82
- *
12-24
8.06 ± 1.82
1.63 ± 0.64
0.73 ± 0.73
24-48
12.33 ± 7.99
0.48 ± 0.48
- *
48-72
0.46 ± 0.13
0.13 ± 0.01
- *
Plasma
72 hrs
0.82 ± 0.11
0.22 ± 0.07
- *
*: not detected
Concentration of chlorine compounds in rat blood:
Rats were sacrificed 1/2 hr after the administration of 10 or 100 mg/lL of 36ClO2. Plasma and packed cells, with and without saline wash were analysed for chlorine compounds.
The total chlorine compounds as percentage of the initial dose in 1 mL plasma or erythrocyte hemolysates were 1.42 ± 0.05, 0.47 ± 0.02, respectively, were detected after a 10 mg/L dose.  The concentration in washed packed cells was 0.15 ± 0.01 and 0.18 ± 0.00 in 100 and 10 mg/L doses, respectively.  In plasma, 36Cl-was 1.17 ± 0.04, and 0.91 ± 0.24 and 36ClO2-was 0.05 ± 0.04 and 0.92 ± 0.1 as percentage of initial doses for the 100 and 10 mg/L doses.

Table 7.1.1/2:Concentration of Chlorine compounds in rat blood 30 min after a ClO2treatment.

100 mg/L of ClO2
10 mg/L of ClO2
Sample analysed
plasma
Packed cells
Washed cells
plasma
Packed cells
Washed cells
Total36Cl
1.42 ± 0.05
0.47 ± 0.02
0.15 ± 0.01
2.22 ± 0.13
0.86 ± 0.03
0.18 ± 0.00
36Cl-
1.17 ± 0.04
-
-
0.91 ± 0.24
-
-
36ClO2-
0.05 ± 0.04
-
-
0.92 ± 0.10
-
-

Applicant's summary and conclusion

Conclusions:
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.
Executive summary:
In two separate metabolism studies, radiolabelled Chlorine Dioxide (36ClO2), was administered to Wistar rats (4 males/dose) by oral route. In the first experiment urine was collected at 12, 24, 48 and 72 hours after administration of 100 mg/L ClO2. Quality and quantity of chlorine compounds were measured in urine and plasma at 72 hours.
In the second experiment, animals were administered ClO2 at dose levels of 10 and 100 mg/L. Since 36ClO2 reaches a peak at 1/2 hour (Abdel-Rhaman, 1980b), animals were killed after 1/2 hour for analysis. Plasma and packed cells, with and without cold saline wash, were analyzed for chlorine compounds.
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.
The decrease of total 36Cl observed after washing packed cells with cold saline suggested that a high percentage of total 36Cl was exchangeable with the chlorine in saline.