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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

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.

Link to relevant study records
Reference
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)
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
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.
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.
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'.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

DBP tested in a vitro study (yeast cells, RL1) did not give any indication for genetic toxicity.

Similiar to that result other in vitro studies gave an indication for a genotoxic effect in one assay, but in the same experiment, this effect was not seen with other dialkylphthalates (a.o. diethylphthalate). No genotoxic effects for dibutylphthalate were observed in in vivo studies detecting chromosomal aberrations.

Based on the data available for dibutylphthalate from a variety of genotoxicity studies as described above and taking into consideration the non-genotoxic properties of other phthalate esters, dibutylphthalate can be considered as a non-genotoxic substance.(1)

DBP is considered to be non-genotoxic based on the weight-of-evidence showing no genotoxicity for DBP in most in vitro and all in vivo tests performed to standard testing guidelines (IPCS 1997; Kleinsasser et al. 2000; ECB 2004). The in vivo tests include sex-linked recessive lethal test in Drosophila and micronucleus assay (according to OECD 474 and comparable standards) in NMRI and B6C3F1 mice.

No adequate long-term carcinogenicity studies with DBP in laboratory animals are available.

Based on the information available for genotoxicity, DBP is not genotoxic and is not likely to be a genotoxic carcinogen. Moreover, in several in vitro cell transformation assays, DBP did not induce cell transformation (Nuodex 1982; Litton Bionetics 1985*; Barber et al. 2000).

DBP is not considered to be carcinogenic to humans when taking into account that the mechanisms by which DBP and hypolipidaemic substances induce peroxisome proliferation in rodents are not considered relevant to humans, and the absence of evidence associating DBP exposure to carcinogenic effects in humans.(2)

(1)

European Union Risk Assessment Report dibutyl phthalate, Volume 29, p. 6 (2003)

Editors: B. G. Hansen, S.J. Munn, R. A/Ianou, F. Berthault, J. de Bruin, M. Luotamo, C. Musset, S. Pakalin, G. Pellegrini, S. Scheen S. Vegro.

Office for Official Publications of the European Communities, ISBN 92—894—1276—3

(2)

Priority Existing Chemical Assessment Report No. 36, Dibutyl phthalate, November 2013, ISBN 978-0-9874434-4-1, p.84

Australian Government, Department of Health

NATIONAL INDUSTRIAL CHEMICALS NOTIFICATION AND ASSESSMENT SCHEME

GPO Box 58, Sydney NSW 2001 AUSTRALIA www.nicnas.gov.au

Justification for classification or non-classification