Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
The effect of RC 9927 (bis(2-ethylhexyl)tetrabromophthalate) on chromosome structure in bone marrow cells was investigated following acute intraperitoneal and sub-acute dermal administration to mice. Chromosome damage was measured indirectly by counting micronuclei.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) tetrabromophthalate
EC Number:
247-426-5
EC Name:
Bis(2-ethylhexyl) tetrabromophthalate
Cas Number:
26040-51-7
Molecular formula:
C24H34Br4O4
IUPAC Name:
1,2-bis(2-ethylhexyl) 3,4,5,6-tetrabromobenzene-1,2-dicarboxylate
Test material form:
liquid
Details on test material:
RC 9927 (batch 6159-199-3), also identified as FR-45B, a slightly turbid, viscous pale yellow liquid received from Pennwalt Corporation on 1st September 1986.

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
dermal
Duration of treatment / exposure:
Intraperitoneal route: animals were killed 48 or 72 hours after treatment.
Dermal route: animals were treated 5 days and killed 18 or 48 hours after the final treatment.
Frequency of treatment:
Intraperitoneal: single treatment.
Dermal: 5 separate treatments (24 hour intervals).
Post exposure period:
None
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 250, 500, 1000, 2000 mg/kg bw
Basis:
nominal conc.
main micronucleus test - intraperitoneal route
Remarks:
Doses / Concentrations:
0, 2000 mg/kg bw
Basis:
nominal conc.
main micronucleus test - dermal application
No. of animals per sex per dose:
Main Micronucleus Test - intraperitoneal route
Group Treatment Dosage Number Animal
(mg/kg) of mice numbers
1 Corn oil - 15M 17 - 31
15 F 62 - 76
2 RC 9927 80 5M 32 - 36
5F 7 - 81
3 RC 9927 400 5M 37 - 41
5F 82 - 86
4 RC 9927 2 000 15M 42 - 56
15F 87 - 101
5 Chlorambucil 30 5M 57 - 61
5F 102 - 106

Main Micronucleus Test - dermal application
Group Treatment Dosage Number Animal
(mg/kg) of mice numbers
6 Corn oil - 10M 107 - 116
10F 127 136
7 RC 9927 2000 10M 117 - 126
10F 137 - 146

Control animals:
yes

Examinations

Tissues and cell types examined:
erythrocytes of bone marrow cells

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Frequencies of micronucleated polychromatic erythrocytes in animals exposed to RC 9927 (bis(2-ethylhexyl)tetrabromophthalate) for 24, 48 or 72 hours via the intraperitoneal route were similar to those in concurrent controls. This lack of treatment-related effect was confirmed by statistical analysis.

Frequencies of micronucleated polychromatic erythrocytes in animals treated dermally for 5 days with RC 9927 (bis(2-ethylhexyl)- tetrabromophthalate) and sacrificed 18 or 48 hours after the final treatment were also similar to those in concurrent controls. Again, statistical analysis confirmed that there was no significant increase in the frequencies of micronucleated polychromatic cells in RC 9927 (bis(2-ethylhexyl)tetrabromophthalate) treated groups compared to concurrent vehicle control groups at either termination time.

Statistically significant increases over controls were seen in positive control group animals given chlorambucil at 30 mg/kg (p < 0.01).

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative
Executive summary:

The effect of RC 9927 (bis(2-ethylhexyl)tetrabromophthalate) on chromosome structure in bone marrow cells was investigated following acute intraperitoneal and sub-acute dermal administration to mice. Chromosome damage was measured indirectly by counting micronuclei.

Frequencies of micronucleated polychromatic erythrocytes in animals exposed to RC 9927 (bis(2-ethylhexyl)tetrabromophthalate) for 24, 48 or 72 hours via the intraperitoneal route were similar to those in concurrent controls. This lack of treatment-related effect was confirmed by statistical analysis.

Frequencies of micronucleated polychromatic erythrocytes in animals treated dermally for 5 days with RC 9927 (bis(2-ethylhexyl)- tetrabromophthalate) and sacrificed 18 or 48 hours after the final treatment were also similar to those in concurrent controls. Again, statistical analysis confirmed that there was no significant increase in the frequencies of micronucleated polychromatic cells in RC 9927 treated groups compared to concurrent vehicle control groups at either termination time.

Statistically significant increases over controls were seen in positive control group animals given chlorambucil at 30 mg/kg (p < 0.01).

Under the conditions of test, there was no evidence of induced chromosomal or other damage leading to micronucleus formation in polychromatic erythrocytes of treated mice, after either acute intraperitoneal or sub-acute dermal administration of RC 9927 (bis(2-ethylhexyl)tetrabromophthalate).

Therefore, the test is negative.