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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:
not reported.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
publication
Title:
Ethylene dibromide: negative results with the mouse dominant lethal assay and the electrophoretic specific-locus test.
Author:
Barnett, L.B., Lovell, D.P., Felton, C.F., Gibson, B.J., Cobb, R.R., Sharpe, D.S., Shelby, M.D. & Lewis, S.E.
Year:
1992
Bibliographic source:
Mutation Research, Vol. 282 (1992), pp. 127-133, © 1992 Elsevir Science Publishers B.V.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
not specified
GLP compliance:
not specified
Type of assay:
rodent dominant lethal assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
EDB (CAS No. 106-93-4) was obtained from the National Institute of Environmental Health Sciences' chemical repository at Radian Corporation,
Austin, TX.

Test animals

Species:
mouse
Strain:
other: Male DBA/2J and female C57BL/6J
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Male DBA/2J and female C57BL/6J mice were obtained from the Jackson Laboratory.
- Age at study initiation: Males: 9 weeks; Females: 12-16 weeks.
- Weight at study initiation: nda
- Assigned to test groups randomly: Randomly sorted by weight.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: Physiological saline.
Details on exposure:
EDB in physiological saline.
Duration of treatment / exposure:
Single intraperitoneal (i.p) injection.
Frequency of treatment:
Single intraperitoneal (i.p) injection.
Post exposure period:
Duration not reported. Offspring sacrificed at 10-12 weeks.
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
40 males
Control animals:
yes, concurrent vehicle
Positive control(s):
- Positive control substance: Procarbazine
- Justification for choice of positive control(s): Previous studies have shown that procarbazine injected intraperitoneally in the mouse at doses of 400 mg/kg induces a high percentage of dominant lethal mutations.
- Route of administration: intraperitoneal (i.p.) injection
- Doses / concentrations: 400 mg/kg (body weight)

Examinations

Tissues and cell types examined:
All females were killed by cervical dislocation and dissected approximately 12 days following removal from the breeding cage and presumptive
mating. The dominant lethal test was based on the following parameters: "Each female was scored for pregnancy and for total number of implants, as comprised by live implants, early fetal deaths, and late fetal deaths. Early fetal deaths are brown or black, containing necrotic and hemorrhagic material but no embryo; contrastingly, late fetal deaths are seen as implantation sites containing a subnormal fetus and placenta which may be white or pale"
Details of tissue and slide preparation:
nda
Evaluation criteria:
The dominant lethal test was based on the following parameters: "Each female was scored for pregnancy and for total number of implants, as comprised by live implants, early fetal deaths, and late fetal deaths. Early fetal deaths are brown or black, containing necrotic and hemorrhagic material but no embryo; contrastingly, late fetal deaths are seen as implantation sites containing a subnormal fetus and placenta which may be white or pale"
Statistics:
Statistical analysis of the dominant lethal test was carried out using one-sided Mann-Whitney U Tests and pooled two sample t-tests to compare
the ratio of frequencies of early deaths in the treated and solvent control groups for each week of mating.
Comparisons of pregnancy rates in the treated groups and the solvent control group were made by a one-sided Fisher exact test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not examined
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The dominant lethal studies showed no effect on the fertility of treated males (Table 2), nor any effects on the development of their progeny.

- Results for the Electrophoretic study:
Fertility of treated males remained normal throughout the breeding period. A total of 49 599 loci were screened from the treated group. As illustrated by the data, EDB produced negative results in the mouse electrophoretic specific- locus test, No mutations were detected among 1503 offspring recovered from the treated group or from the 335 solvent control animals.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The dominant lethal studies showed no effect on the fertility of treated males, nor any effects on the development of their
progeny.