Diisooctyl adipate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP - guideline study with acceptable restrictions. Cytotoxicity was not determined in the main study.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1996

Reference 2

Reference Type:

secondary source

Title:

Dibutyl adipate CAS N°: 105-99-7

Author:

OECD

Year:

1996

Bibliographic source:

SIDS Initial Assessment Report for SIAM 4; Tokyo, Japan, 20-22 May 1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

(adopted in 1983)

Deviations:

yes

Remarks:

Cytotoxicity was tested separately from the main CA test

Test guideline 2

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Deviations:

yes

Remarks:

Cytotoxicity was tested separately from the main CA test

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyl adipate

EC Number:

203-350-4

EC Name:

Dibutyl adipate

Cas Number:

105-99-7

Molecular formula:

C14H26O4

IUPAC Name:

dibutyl adipate

Details on test material:

- Name of test material (as cited in study report): Dibutyl adipate
- Analytical purity: 99.8%

Method

Target gene:

not applicable

Species / strain

Species / strain / cell type:

mammalian cell line, other: Chinese hamster lung (CHL/IU) cells

Details on mammalian cell type (if applicable):

- Type and identity of media: MEM medium plus 10% foetal calf serum plus L-glutamine

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital and 5,6-Benzoflavone.

Test concentrations with justification for top dose:

-S9
6 h treatment: 0.012, 0.023, 0.046 mg/mL
24 h treatment: 0.7, 1.3, 2.6 mg/mL
48 h treatment: 0.7, 1.3, 2.6 mg/mL

+S9
6 h treatment: 0.7, 1.3, 2.6 mg/mL

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: mitomycin C, 0.05 µg/mL, -S9 and + S9; cyclophosphamide, 5 µg/mL

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 6 , 24 and 48 h
- Fixation time (start of exposure up to fixation or harvest of cells): 4, 22 and 46 h

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 200

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

OTHER EXAMINATIONS:
- Determination of polyploidy: yes

Evaluation criteria:

Judge was made on the basis of incidence as; -: negative (less than 5.0%); ±: equivocal (5.0% or higher to less than 10.0%); +: positive (10.0% or higher)

Results and discussion

Test results

Test results 1

Species / strain:

mammalian cell line, other: Chinese hamster lung (CHL/IU) cells

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

0.7 mg/mL

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

mammalian cell line, other: CHL/IU

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

0.7 mg/mL

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Results of the experiment

Test item	Concentration	Mitotic Index by cytotoxicity test	Aberrant cells in %
	in µg/mL	in %	with gaps	without gaps
Exposure period 24 h, without S9 mix
control	0		0.5	0.5
DMSO	0	100	0.5	0.5
MMC	0.05	-	50.5	50.0
Test substance	700	no data	0.5	0.5
	1300	no data	1	1
	2600	no data	2	2
Exposure period 48 h, without S9 mix
DMSO	0	100	0	0
MMC	0.05	-	45.5	45.5
Test substance	700	65.0	1.5	1.5
	1300	52.5	1	1
	2600	47.0	2	2
Exposure period 6 h, without S9 mix
control	0		0.5	0.5
DMSO	0	100	0.5	0
CP	5	-	0	0
Test substance	12	98	1	1
	23	87.5	0.5	0
	46	30.5	2	1.5
Exposure period 6 h, with S9 mix
DMSO	0	100	2	1.5
CP	5	-	82	82
Test substance	700	73	6.5	5.5
	1300	54	12	11
	2600	44	3.5	3

CP: cyclophosphamide

MMC: mitomycin C

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive with metabolic activation
negative without metabolic activation