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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed in accordance with the OECD guideline 474, and in compliace with GLP standard.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
not specified
Principles of method if other than guideline:
NA
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): 4,4'-oxybis(benzenesulfonyl hydrazide)
- Analytical purity: no data
- Purity test date: 97.6%
- Lot/batch No.: 08929DR

Test animals

Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: 8 weeks
- Weight at study initiation: 28.5 - 36.0 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: MC (methyl cellulose)
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: no data
- Amount of vehicle (if gavage or dermal): 0.5% MC
- Type and concentration of dispersant aid (if powder): no data
- Lot/batch no. (if required): 126H0394
- Purity: no data
Details on exposure:
no data
Duration of treatment / exposure:
two treatments at 24 hour intervals
Frequency of treatment:
duplicate treatments (positive control group was dosed once)
Post exposure period:
24 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 375, 750 and 1500 mg/kg bw/day
Basis:

No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide.H2O
- Justification for choice of positive control(s): no data
- Route of administration: intraperitoneal injection
- Doses / concentrations: 70mg/kg

Examinations

Tissues and cell types examined:
erythrocytes
Details of tissue and slide preparation:
no data
Evaluation criteria:
At least 2,000 polychromatic erythrocytes per animals were scored for the incidence of micronuclei.
There are several criteria for determining a positive result, such as a dose-related increase in the number of micronucleated cells or a clear increase in the number of micronucleated cells in a single dose group at a single sampling time.
Statistics:
To compare the results of the control and treatment groups, Kruskal-Wallis’ H-test was carried out. If this result was significant, Dunnett’s t-test was conducted to find out significance. If there was a significant difference, Cochran-Armitage trend test was conducted to confirm the dose-dependency. Mann-Whitney’s U-test was carried out to compare the results of the control and positive controls.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not examined
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Additional information on results:
All animals dosed with OBSH exhibited similar PCE/(PCE + NCE) ratios and MNPCE frequencies compared to those of negative control animals (p > 0.01). All frequencies of MNPCE in the negative control groups fell within acceptable ranges, while the positive control groups induced clear increase in the frequencies of MNPCE.

Any other information on results incl. tables

Table. Summary of PCE/(PCE+NCE) ratio and MNPCE frequency

Treatment group

Dose (mg/kg)

No. of Animal

 PCE/(PCE+NCE)

(mean±S.D.)

MNPCE per2,000 PCE

(mean±S.D.)

Vehicle(0.5 % methyl cellulose)

      0

6

0.43 ( 0.11

0.67 ( 0.82

OBSH

  375

6

0.47 ( 0.04

0.67 ( 0.82

 

  750

6

0.47 ( 0.05

1.00 ( 0.89

 

1,500

6

0.45 ( 0.03

1.33 ( 0.82

Cyclophosphamide

    70

6

0.37( 0.04

75.50 ( 22.41*

*: Significant difference from the control at p < 0.01

MNPCE; Micronucleated polychromatic erythrocyte,

PCE; Polychromatic erythrocyte,

NCE; Normochromatic erythrocyte,

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The genetic toxicity in vivo of OBSH was evaluated in a Mammalian erythrocyte micronucleus test. The test was performed in accordance with the OECD guideline 474. It was concluded that OBSH did not induce micronuclei in the mice bone marrow cells.
Executive summary:

The genetic toxicity in vivo of OBSH was evaluated in a Mammalian erythrocyte micronucleus test. The test was performed in accordance with the OECD guideline 474.

All animals dosed with OBSH exhibited similar PCE/(PCE + NCE) ratios and MNPCE frequencies compared to those of negative control animals (p > 0.01). All frequencies of MNPCE in the negative control groups fell within acceptable ranges, while the positive control groups induced clear increase in the frequencies of MNPCE.

It was concluded that OBSH did not induce micronuclei in the mice bone marrow cells.