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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro DNA damage and/or repair study
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 455: "Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists", adopted 02. Oct. 2012
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
(Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Kaiser-Friedrich-Straße 7, 55116 Mainz, Germany)
Type of assay:
yeast cytogenetic assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: oily liquid
Details on test material:
Purity > 99%
Homogeneity homogeneous
Stability stable at room temperature
Solubility soluble in DMSO
Production date not stated
Expiry date Nov. 2018
Storage room temperature

Method

Species / strain
Species / strain / cell type:
Saccharomyces cerevisiae
Additional strain / cell type characteristics:
other: Mutations hERalpha and hAR receptor, expression plasmid carrying the reporter gene lacZ
Test concentrations with justification for top dose:
Dosage of Test Item
Eight concentrations with half-log dilutions were tested in duplicate. A stock solution containing 0.01 mol/L in DMSO was prepared for the serial dilution.
The following concentrations were tested: 3.16*10-8, 1.00*10-7, 3.16*10-7, 1.00*10-6, 3.16*106, 1.00*10:5, 3.16*10-5, 1.00*10-5, 3.16*10-5, 1.00*10-4 mol/1
Vehicle / solvent:
Dimethyl sulfoxide (DMSO) was used as a solvent for the test item and for the positive controls.
Controlsopen allclose all
Positive controls:
yes
Positive control substance:
other: 17ß-estradiol (E2):
Remarks:
YES Agonist Assay
Positive controls:
yes
Positive control substance:
other: 4-hydroxytamoxifen (HT)
Remarks:
YES Antagonist Assay
Positive controls:
yes
Positive control substance:
other: 5alpha-dihydrotestosterone (DHT)
Remarks:
YAS Agonist Assay
Positive controls:
yes
Positive control substance:
other: Flutamide (FL)
Remarks:
YAS Antagonist Assay
Details on test system and experimental conditions:
Dimethyl sulfoxide (DMSO) was used as a solvent for the test item and for the positive controls.

Results and discussion

Test results
Species / strain:
Saccharomyces cerevisiae
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Positive and solvent controls showed the expected results.
After incubation with test item and yeast cells, no cytotoxicity was observed. The growth factor was within the expected range (> 0.5).
Dibutyl phthalate showed no endocrine activity, neither in the YES Assay nor in the YAS Assay: The values for galactosidase activity and induction ratio of all test item dilutions lay in the same range as the values of the respective control. No dose-response correlation was visible.

Under the conditions of this test system, the test item Dibutyl phthalate is considered to have neither estrogenic nor androgenic agonistic or antagonistic activity in the YES YAS Assay.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

After incubation with test item, no cytotoxicity was observed for the yeast cells.

The values for galactosidase activity and induction ratio of all test item dilutions lay in the same range as the values of the respective control. No dose—response correlation was visible. Dibutyl phthalate showed no endocrine activity, neither in the YES Assay nor in the YAS Assay.

Under the conditions of this test system, the test item Dibutyl phthalate is considered to have neither estrogenic nor androgenic agonistic or antagonistic activity in the YES YAS Assay.

The value for the positive controls were within the range of historical data of the test facility *

Some of the OD values of the solvent controls were not within the range of historical data of the test facility *. This is considered as uncritical for the following reason: The deviation from the respective range of the historical data was only marginal. Variation of biological systems within this order of magnitude is not unusual. For these reasons, the result ofthe test is considered as valid.
* See PDF 'Historical data' under 'Attached background material' above.