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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 5-11-1984 to 6-20-1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions.
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:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
yes
Remarks:
: number of males inferior as what is advocated in guideline No.478, females are housed with treated males for a total of 5 days.
Principles of method if other than guideline:
The potential of Chlorine dioxide to produce germ cell mutations in male mice was evaluated for the mouse dominant lethal assay. Chlorine dioxide was given to male mice as an aqueous solution by intraperitoneal injection, at either 2, 7, or 20 mg/kg. Three days after dosing, the males were sequentially mated to two females per week for 4 weeks.
GLP compliance:
not specified
Type of assay:
rodent dominant lethal assay

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:
- Name of test material (as cited in study report): Chlorine dioxide
- Substance type: no data
- Physical state: Clear yellow aqueous solution
- Analytical purity: no data
- Lot/batch No.: 8892C
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature in the dark (protected from light using opaque containers at all times)

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, New York, USA.
- Age at study initiation: Young adults, 6 weeks of age when received
- Weight at study initiation: male mice weighed 31.5 g (mean) before the dosing
- Assigned to test groups randomly: yes, under following basis: according to Litton Bionetics, Inc. (LBI) Standard Operating Procedures (SOP) No. 303.
- Fasting period before study: no data
- Housing: up to 15 mice per cage
- Diet (e.g. ad libitum): ad libitum(Purina Certified Laboratory Chow) (unless contraindicated by the particular experimental design).
- Water (e.g. ad libitum): ad libitum (unless contraindicated by the particular experimental design).
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs-12 hrs

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Glass-distilled, deionized water
Details on exposure:
Dose applied: 2, 7, 20 mg/kg
Duration of treatment / exposure:
No data
Frequency of treatment:
Number of applications: 1
Post exposure period:
Females were killed 14 days after the midweek of mating.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.290; 1.020 and 2.895 mg/mL
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
2.786; 0.967 and 0.264 mg/mL
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
1.84; 6.76 and 19.46 mg/kg
Basis:
analytical conc.
No. of animals per sex per dose:
12 males /group
Control animals:
yes, concurrent vehicle
Positive control(s):
Triethylenemelamine (TEM) at 0.3 mg/kg as an aqueous solution.

Examinations

Tissues and cell types examined:
Clinical signs: Premature death at 20 mg/kg

Tissue: Germ cells
Number of animals: 12 or 15 animals per dose level
Number of cells: N/A
Time points: 1, 2, 3 and 4 weeks post dosing
Type of cells male germ cells
Parameters: For each pregnant female, the number of living, dead and total implantations counted and recorded.
Details of tissue and slide preparation:
No data
Evaluation criteria:
No data
Statistics:
No data

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
20 mg/kg was a lethal dose, causing death in 47% of the mice
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
Chlorine dioxide at 20 mg/kg was a lethal dose, causing death in 47% of the mice and a significant decrease in male fertility in the surviving mice at mating weeks 1, 2 and 4. It is unknown whether the decrease in male fertility was a direct effect on the male reproductive system or an indirect effect due to systemic toxicity. ClO2 at 2 and 7 mg/kg did not cause any observable signs of toxicity and did not affect male fertility. Compared to the negative control, ClO2 at either 2, 7, or 20 mg/kg did not decrease the number of total implants per female, did not increase the mean number of dead implants per female, did not increase the proportion of females with one or more, or two or more dead implants and did not result in greater mutation index (ratio of dead implants to total implants). Chlorine dioxide was not mutagenic under the conditions tested in the mouse dominant lethal assay.

Any other information on results incl. tables

Table 7.6.2/1: Results of the Mouse dominant lethal assay

Week

Parameter

Negative control

ClO2

(2 mg/kg)

ClO2

(7 mg/kg)

ClO2

(20 mg/kg)

Positive control

 

Total number of males dosed

12

12

12

15

12

Number of males dead

0

0

0

7

0

1

Number of mated females

24

24

24

24

24

Number of pregnant females

21

21

19

3

14

Mean of implants per female

10.76

10.81

11.47

10.67

7.86*

Mean of dead implants

0.24

0.81**

0.47

1.33

6.50*

Proportion of females with 1 or more dead implanta

5

12

6

3

14

2

Number of mated females

24

24

24

18

24

Number of pregnant females

22

23

21

6

7

Mean of implants per female

10.91

12.09

12.29

11.00

3.86*

Mean of dead implants

0.59

0.61

0.52

0.50

2.86*

Proportion of females with 1 or more dead implanta

9

10

8

2

7

3

Number of mated females

24

24

24

18

24

Number of pregnant females

21

22

23

10

18

Mean of implants per female

12.52

12.68

13.22

10.80

11.22

Mean of dead implants

0.62

0.77

0.83

0.80

3.06*

Proportion of females with 1 or more dead implanta

9

14

11

6

15

4

Number of mated females

24

24

24

16

24

Number of pregnant females

22

19

22

9

21

Mean of implants per female

12.27

12.53

12.73

11.89

11.33

Mean of dead implants

0.59

1.16

1.23

0.67

0.76

Proportion of females with 1 or more dead implanta

10

11

13

5

11

a: Total number of females with one or more dead implants for all pregnant females in the study group.

*: Significantly greater (P<0.01) in comparison to the negative control by Dunett’s T-test

**: Significantly greater (P<0.05) in comparison to the negative control by Dunett’s T-test

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Uner the test conditions, the chlorine dioxide was not mutagenic in the mouse dominant lethal assay.
Executive summary:

In an in vivo mouse dominant lethal assay, performed according to the OECD guideline No. 478, male CD-1 mice were exposed to Chlorine Dioxide by a single intraperitoneal injection at doses of 2, 7 and 20 mg/kg bw.

Vehicle was glass-distilled, deionized water. Concurrent vehicle animals were used as a negative control and the positive control was Triethylenemelamine (TEM) at 0.3 mg/kg as an aqueous solution. The controls gaven acceptable results.

Male germ cells were examined at 1, 2, 3 or 4 week post dosing, and for each pregnant female, the number of living, dead and total implantations was counted and recorded.

Genotoxicity results were negative for Chlorine Dioxide to male CD-1 mice whereas toxicity results were positive. Chlorine dioxide at 20 mg/kg was a lethal dose, causing death in 47% of the mice and a significant decrease in male fertility in the surviving mice at mating weeks 1, 2 and 4. It is unknown whether the decrease in male fertility was a direct effect on the male reproductive system or an indirect effect due to systemic toxicity.

ClO2 at 2 and 7 mg/kg did not cause any observable signs of toxicity and did not affect male fertility. Compared to the negative control, ClO2 at either 2, 7, or 20 mg/kg did not decrease the number of total implants per female, did not increase the mean number of dead implants per female, did not increase the proportion of females with one or more, or two or more dead implants and did not result in greater mutation index (ratio of dead implants to total implants).

Under the test conditions, the chlorine dioxide was not mutagenic in the mouse dominant lethal assay.

This study is classified as acceptable as satisfies with the requirements for Test Guideline OECD 478 for Rodent Dominant Lethal Test.