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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, near-guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
yes
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test article I.D.: K0698.01
Lot number: not provided

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley Inc., Frederick, MD
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 267-339 g (males), 206-259 g (females)
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Diet: Rodent chow, ad libitum
- Water: from a municipal water supply, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
distilled water
Details on exposure:
Male and female Sprague-Dawley rats were treated with the substance at dose volumes of 1.6, 5.3 or 16 mL/kg body weight which was given as a single gavage administration. A cell cycle kinetics study indicated that the substance had no adverse effects on bone marrow cell cycle kinetics following acute administration of the high dose level.
Duration of treatment / exposure:
single administration
Frequency of treatment:
once
Post exposure period:
6 or 12 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
1.6, 5.3, 16 mL/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
other: yes, distilled water
Positive control(s):
cyclophosphamide (CP)
2'-5'-bromodeoxyuridine (BrdU)

Examinations

Tissues and cell types examined:
Bone marrow cells
Details of tissue and slide preparation:
Bone marrow cells arrested in the metaphase and collected 6 or 12 hours after administration were examined microscopically for numerical and structural chromosome aberrations.
Evaluation criteria:
The test article is considered to induce a positive response when the number of aberrations per cell at any dose or doses is significantly increased relative to the vehicle centrol. A significant trend test (pā‰¤0.05, Cochran-Armitage Test) only, with no single dose significantly increased, is considered equivocal.
Statistics:
Male and female animals ware analyzed separately. The Fisher's Exact Test was used to compare the percentage of aberrant ceIls between each animal and it's corresponding vehicle control group. The Wilcoxon's Rank Sum Test was used to compare the average number of aberrations per cell per animal in each treatment group to the appropriate vehicle control group. The Cochran-Armitage Trend Test was employed to test for evidence of a dose response between groups at each sacrifice time point.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The substance did not induce numerical and structural chromosome aberrations.

Applicant's summary and conclusion