Freitag, 26. Februar 2016

Repeated dose toxicity: oral.002 to 003

Repeated dose toxicity: oral.002

Administrative data

Study result type:
experimental result
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
Few information on the study design and on the results. No data on concentrations tested. Only gross pathology examined.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Principles of method if other than guideline:
Male and female mice were exposed chlorine dioxide via the drinking water for 30 days at two concentrations. At the end of the exposure period, a necropsy was performed on each animal to examine it for gross pathological changes.
GLP compliance:
no data
Test type:
subacute
Limit test:
no

Test materials

Identity of test material same as for substance defined in section 1 (if not read-across):
yes
Test material identityopen allclose all
Identifier:
CAS number
Identity:
10049-04-4
Identifier:
EC name
Identity:
233-162-8
Identifier:
IUPAC name
Identity:
chlorine dioxide
Details on test material:
- Name of test material (as cited in study report): chlorine Dioxide
- Physical state: liquid
- 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 concentrated drinking water samples to be used for toxicological testing were collected and concentrated at a pilot-scale drinking water treatment plant in Jefferson Parish, LA, USA. The influent stream was split into 5 separate process streams. The process streams were untreated or disinfected etiher with ozone, chlorine dioxide (ClO2), monochloramine, or with chlorine. The stream disinfected with ClO2 contained 0.5 mg/L ClO2 residual after the treatment. Then two methods, reverse osmosis and macroreticular resin process were used to collect and concentrate organic compounds from drinking water before toxicological testing.
For the inititation/promotion assay, the study was performed on disinfected water with ClO2 and concentrated via reverse osmosis.

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
30 days
Frequency of treatment:
no data, but probably daily
Doses / concentrations
Doses / concentrations:
the aqueous samples were administered as drinking water in concentrations equal to the original concentrate (400X) and one-fourth of the original concentrate (100X).
Basis:
nominal in water
No. of animals per sex per dose:
10 animals/sex/dose
Control animals:
yes

Results and discussion

Results of examinations

Any other information on results incl. tables:
Taste aversion to the reverse osmosis concentrate was not seen in the study. In fact, significant increases in fluid consumption was detected in female exposure group. Statistically significant differences in the body weights was found for a male group, but the difference was caused by a difference in initial body weight. Since the data and necropsy reports did not reveal any overt, subschronic toxicity, histopathological examination of major organs was not performed.
Table 7.5.1/1: Results of the oral subacute study
Mice
Sample
Concentration
Fluid consumed
Final body weight
Brain/body weight
Kidney/body weight
Liver/body weight
Lung/body weight
ovaries/body weight
Testes/body weight
spleen/body weight
spleen/brain
Female
Nondisinfected water
100X
-
-
-
-
-
Not applicable
-
No data
400X
-
-
-
-
-
Not applicable
No data
Chlorine dioxide
100X
-
-
-
-
-
Not applicable
-
No data
400X
-
-
-
-
-
-
-
Not applicable
-
No data
Male
Nondisinfected water
100X
-
-
No data
-
-
Not applicable
-
No data
-
400X
-
-
No data
-
-
-
Not applicable
-
No data
-
Chlorine dioxide
100X
-
-
No data
-
-
-
Not applicable
-
No data
-
400X
-
No data
-
-
-
Not applicable
-
No data
-
-: no significant difference
↑: statistically significant increase (P<0.05)
↓: statistically significant decrease (P<0.05)

Applicant's summary and conclusion

Conclusions:
Under the test conditions, repeated exposure to chlorine dioxide treated water by oral route had no effect on mice gross-pathology.
Executive summary:
In a subacute toxicity study, Chlorine Dioxide (ClO2) treated water was administered in drinking water to CD-1 male and female mice (10 animals/sex/dose) at two different concentrations (100 and 400 X), for a period of 30 consecutive days. A control group received nondisinfected water .
At the end of the exposure period, animals were sacrificed and fluid consumtion, the final body weight, and the ratio of organ weight to body weight of many organs (Brain, Kidney, Lung, Ovaries, Spleen, Testes) were examined.
Under the test conditions, repeated exposure to chlorine dioxide treated water by oral route had no effect on mice gross-pathology.

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