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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo, other
Remarks:
Type of genotoxicity: other: Sperm-head anomalies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Test method was not according to any guideline. No data on GLP.

Data source

Reference
Reference Type:
publication
Title:
Evaluation of Chemicals Used for Drinking Water Disinfection for Production of Chromosomal Damage and Sperm-Head Abnormalities in Mice
Author:
Meier JR, Bull RJ, Stober JA, Cimino MC
Year:
1985
Bibliographic source:
Environmental Mutagenesis 7:201-211.

Materials and methods

Principles of method if other than guideline:
Male B6C3F1 mice (10 per group) were administered total doses of 0.2, 0.5 or 1 mg sodium chlorite by gavage in five equal daily doses. Positive controls received 200 mg ethyl methanesulfonate/kg bw intraperitoneally in five equal doses. Animals were sacrificed 1, 3 and 5 weeks after dosing, and the caudae epididymides were removed and diced in saline. Tissue fragments were filtered out, and 1000 sperm heads were scored per animal for abnormalities.
GLP compliance:
not specified
Type of assay:
other: Sperm-head anomalies

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium chlorite
EC Number:
231-836-6
EC Name:
Sodium chlorite
Cas Number:
7758-19-2
Molecular formula:
ClHO2.Na
IUPAC Name:
sodium chlorite
Details on test material:
- Name of test material (as cited in study report): Sodium chlorite, NaClO2.
- Analytical purity: reagent grade chemical

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River: Harlan Industries, Inc.
- Age at study initiation: 8-11-week-old-
Housing: Animals were group housed, separated by treatment group.
- Diet (e.g. ad libitum): Animals were allowed food (Purina Laboratory Chow) ad libitum.
- Water (e.g. ad libitum): Ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: waterAnimals were dosed with 1 mL of test solution.
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Solutions were prepared gravimetrically in distilled water at concentrations of 1000 mg/L, 500 mg/L, and 200 mg/L.
Duration of treatment / exposure:
5 days.
Frequency of treatment:
Daily (approximately 24 hr apart).
Post exposure period:
Animals were sacrificed 1, 3 and 5 weeks after dosing.
Doses / concentrationsopen allclose all
Dose / conc.:
10 mg/kg bw/day (actual dose received)
Remarks:
0.2 mg/day
Dose / conc.:
25 mg/kg bw/day (actual dose received)
Remarks:
0.5 mg/day
Dose / conc.:
50 mg/kg bw/day (actual dose received)
Remarks:
1 mg/day
No. of animals per sex per dose:
Ten male mice were used for each treatment group (three dose levels of the test solution and controls).
Control animals:
yes, concurrent vehicle
Positive control(s):
Positive controls received 200 mg ethyl methanesulfonate/kg bw intraperitoneally in five equal doses.A positive control was used for each kill time.- The intraperitoneal (IP) route was used for administration of the positive control chemicals since this route was found to be suitable for eliciting consistent and effective responses.

Examinations

Tissues and cell types examined:
Mouse sperm.
Details of tissue and slide preparation:
The caudae epididymides were removed and diced in saline. The suspension was gently pipetted five to six times in and out of a 5- or 10-mL pipette. The suspension was strained through a 80-µm silk mesh to remove tissue fragments, and 0.5 mL of the filtrate was stained in a centrifuge tube with 0.05 mL 1 % Eosin Y. Slides were prepared from this suspension by spreading a drop over the slide with three passes of the edge of another slide.One thousand sperm-heads (500 by each of two readres) were scored per animal, where possible, for sperm-head shape abnormalities using the categories of Wyrobek and Bruce (1975).
Evaluation criteria:
A positive response was based upon a significant increase at any dose level over the concurrent control using a significance levelof 0.05.
Statistics:
Either an analysis of variance procedure or Student's t-test (a = 0.01) was used to analyze the data for differences in the percent sperm-head abnormalities per animal between treated animals and concurrent controls. In the case where reader differences were to be examined, a two-way (dose and reader) analysis of variance was done. Outliers were excluded from the analysis, as recommended by Soares et al (1979), using Dixon's Test for Outliers (1969) on the set of scores for each reader at each dose level. An arcsin transformation of the data was used to stabilize the variance for the analysis of variance.

Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

No treatment-related effects were observed.

Applicant's summary and conclusion

Conclusions:
No treatment-related effects were observed.
Executive summary:

Male B6C3F1 mice (10 per group) were administered total doses of 0.2, 0.5 or 1 mg sodium chlorite by gavage in five equal daily doses. Positive controls received 200 mg ethyl methanesulfonate/kg bw intraperitoneally in five equal doses. Animals were sacrificed 1, 3 and 5 weeks after dosing, and the caudae epididymides were removed and diced in saline. Tissue fragments were filtered out, and 1000 sperm heads were scored per animal for abnormalities.

No treatment-related effects were observed.