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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
data taken from EU RAR
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: taken from EU RAR
Qualifier:
no guideline available
Principles of method if other than guideline:
n/A
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 100
Details on mammalian cell type (if applicable):
100-2,000 μg/plate
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1535
Details on mammalian cell type (if applicable):
100-2,000 μg/plate
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Test concentrations with justification for top dose:
100-10,000 μg/plate
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Conclusion on mutagenicity

In assays detecting gene-mutations in bacteria one assay was negative in all 4 strains tested without and with metabolic activation. In two other assays equivocal and positive results, respectively were seen in strain TA 100 only, without metabolic activation. The positive effects were weak and seen at cytotoxic doses.

A gene-mutation test in yeast cells showed negative results.

In a mouse lymphoma assay performed only without metabolic activation, gene-mutations were induced at highly cytotoxic concentrations. An adequately performed test for gene-mutations in mouse lymphoma cells showed negative effects without metabolic activation; with metabolic activation positive effects were seen. In the same experiment (Hazleton, 1986) diethyl phthalate showed negative results while it is expected that, based on structure-activity relationships, mutagenic activity would increase with decreasing length of the alkyl chain. Also butylbenzyl-, di(2-ethylhexyl)-, diisononyl- and diisodecyl phthalate showed negative results in the same

experiment.

No chromosomal aberrations in mammalian cells were seen but the tests were performed without metabolic activation only. In one test also the induction of SCE's was studied and a slight (<2x), but statistically significant increase of SCE's was seen at all three dose-levels, but without any dose-relationship.

A micronucleus study performed according to current standards showed negative results. In mice exposed for 13 weeks to DBP in their diet no induction of micronuclei was observed either.

In conclusion in vitro studies gave an indication for a genotoxic effect in one assay, but this effect was not seen with other dialkyl phthalates in the same experiment, a.o. with diethyl phthalate. No genotoxic effects for dibutyl phthalate were observed in in vivo studies detecting chromosomal aberrations.

Based on the data available for dibutyl phthalate from a variety of genotoxicity studies as described above and taking into consideration the non-genotoxic properties of other phthalate esters, dibutyl phthalate can be considered as a non-genotoxic substance (EU RAR Dibutyl phthalate, 2004).

Justification for classification or non-classification

Based on the data above the substance does not need to be classified according to EC criteria.