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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
endocrine system modulation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study does not meet standard guidelines. However, the calculation method of T4 levels may be acceptable. Further, the effects on thyroid levels were comparable in both rats and monkeys (see corresponding reference). The authors of the study should also be taken into account (US EPA).
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Effects of chlorine dioxide on thyroid junction in the African green monkey and the rat.
Author:
Harrington RM, Schertzer HG, Bercz JP
Year:
1986
Bibliographic source:
Journal of Toxicology and Environmental Health, 19: 235-242

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
During a preliminary experiment, six female African Green monkeys were exposed to 100 ppm chlorine dioxide in their drinking water for 8 weeks. Before and after treatment, and 3 months after the cessation of treatment, radioactive iodide uptake was performed in each animal by intravenously injecting 1x10E6 cpm/kg body weight of 131 Nal and measuring the 131-I activity of the thyroid gland 24 hours alter. In a second experiment, one year later, the same monkeys were again expsoed to 100 ppm chrlorine dioxide in their drinking water for 8 weeks. Again, radioactive iodine uptake by the thyroid was measured before and after treatment. In addition, blood samples were taken at 0, 4 and 8 weeks of treatment for T4 analysis.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
basic toxicokinetics
repeated dose toxicity: oral

Test material

Constituent 1
Chemical structure
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 generated from sodium chlorate and hydrogen peroxide in the presence of a strong acid
Details on test material:
No data

Test animals

Species:
monkey
Strain:
other: African Green Monkey (Cercopithecus aethiops)
Sex:
female
Details on test animals or test system and environmental conditions:
Source: no data
Age: no data
Weight at study initiation: 3.2 to 5.5 g
Food consumption: fed daily with 15% portion of Purina Moneky chow and fresh fruit.

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
Preliminary experiment: 8 weeks
Second experiment: 8 weeks
Frequency of treatment:
Ad libitum
Post exposure period:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:
100 ppm
Basis:
nominal in water
No. of animals per sex per dose:
6 female monkeys
Control animals:
no
Details on study design:
No data

Examinations

Examinations:
Preliminary experiment: Before and after treatment and 3 months after the cessation of treatment, radioactive iodide uptake was performed in each animal by intravenously injecting 1 x 10E6 cpm/kg body weight of 131-I activity of the thyroid gland 24 hours later.
Second experiment: the same monkeys were again exposed to 100 ppm chlorine dioxide in their drinking water for 8 months. Again, radioactive iodine uptake by the thyroid was measured before and after the treatment. In addition, blood samples were taken at 0, 4 and 8 weeks of treatment for T4 analysis.
Positive control:
No data

Results and discussion

Details on results:
In the preliminary study, radioactive iodide uptake by the thyroid increased approximately 70% after 8 weeks of treatment. Three months after treatment had stopped, the iodine uptake levels had returned to pretreatment levels.
In the second study, one year later, a smaller increase in radioactive iodine uptake was observed. Blood analysis showed T4 levels to decline after 4 weeks of treatment, but then to rebound to significantly above pre-treatment levels by 8 weeks.

Any other information on results incl. tables

The authors noted that the observed T4 rebound phenomenon and increased iodine uptake maybe due to a compensatory endocrinological mechanism.

Applicant's summary and conclusion

Conclusions:
ClO2 had an effect on thyroid parameters (decrease in T4 levels and iodide uptake). However, the T4 levels returned to above normal levels after 8 weeks of dosing. This may be explained by a simple endocrinological compensatory mechanism and suggests a reversible effect of ClO2 on the thyroid.
Executive summary:

In a subchronic toxicity study, Chlorine Dioxide (ClO2) was administered to six female African Green monkeys in drinking water at dose level of 100 ppm for eight weeks. A same preliminary study was performed with the same six female monkeys, and before and after treatment, and three months after the cessation of treatment, radioactive iodide uptake was performed. In the second study, the same monkeys were again exposed to 100 ppm chlorine dioxyde, one year later, in their drinking water for height weeks.

Again, radioactive iodine uptake by the thyroid was measured before and after treatment. In addition, blood samples were taken at 0, 4 and 8 weeks of treatment for T4 analysis.

In the preliminary study, radioactive iodide uptake by the thyroid increased approximately 70% after 8 weeks of treatment. Three months after treatment had stopped, the iodine uptake levels had returned to pre-treatment levels. In the second study, one year later, a smaller increase in radioactive iodine uptake was observed. Blood analysis showed T4 levels to decline after 4 weeks of treatment, but then to rebound to significantly above pre-treatment levels by 8 weeks. It is noted that the observed T4 rebound phenomenon and increased iodine uptake may be due to a compensatory mechanism and suggests a reversible effects of ClO2 on the thyroid.