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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

A Bacterial reverse mutation assay with 4 Salmonella strains, an in vitro chromosome aberration study and in vitro mammalian cell gene mutation test are available with 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol. All showed negative results, although in the chromosome aberration study an increase in polyploid cells was observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

All three in vitro studies required were performed according to OECD test guidelines. In all tests toxicity was observed at concentrations tested with and without metabolic activation. Substance 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol shows no mutagenic activity in a bacterial reverse mutation assay with Salmonella strains, with and without metabolic activation. Under the test conditions, 1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2 –ol did not show mutagenic activity at the HGPRT gene locus, both in the absence and in the presence of metabolic activating system. Based on the observed increases in aberrant cells only when gaps were included (-S9 mix) or in the presence of significant toxicity, 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol is considered to be not clastogenic. In the presence of S9-mix an increase in aberrant cells was only shown in the presence of marked cytotoxicity, thus it was concluded that the substance did not show evidence of clastogenic activity. However, since an increase in the incidence of polyploid cells was observed in the presence of S9-mix (both at 24h and at 48h), 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol may have the potential to disturb mitotic processes and cell cycle progression.

Thus, 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol was then tested in a Micronucleus Test in mice, to evaluate its genotoxic effect in developing erythrocytes (polychromatic erythrocytes) in the bone marrow. The study procedures used were based on the most recent OECD and EC guidelines.

In the dose range finding test, in total three male and three female animals were dosed with 2000 mg/kg of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol dissolved in propylene glycol. The animals showed the following toxic signs: rough coat (2 males, 1 female) and lethargy (1 male, 1 female). Within 20 hours after dosing these animals had recovered from the treatment. No treatment related signs of toxicity were observed in 1 male and 2 female animals. Since there were no substantial differences between sexes in toxicity, only males were used in the main study.

In the main study male animals were dosed on two consecutive days via oral gavage with vehicle or with 2000, 1000 and 500 mg/kg of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol. Two positive control groups were dosed once via oral gavage with 40 mg/kg cyclophosphamide (CP)or 9 mg/kg vinblastin. In total 6 treatment groups were used, each consisting of 5 animals.

No treatment related clinical signs or mortality were noted in any animal treated with 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol or control animals receiving vehicle, cyclophosphamide or vinblastin with the exception of 2 animals dosed with 2000 mg/kg of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol which showed lethargy within 2.5 hours after the second dosing. Both animals had recovered from the treatment within 24 hours after the second dosing.

Bone marrow of all groups was sampled 48 hours after the first dosing.

No increase in the mean frequency of micronucleated polychromatic erythrocytes was observed in the bone marrow of animals treated with 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol compared to the vehicle treated animals.

The incidence of micronucleated polychromatic erythrocytes in the bone marrow of all negative control animals were within the historical vehicle control data range. Cyclophosphamide and vinblastin, the positive control substances, induced statistically significant increases in the number of micronucleated polychromatic erythrocytes. Hence, both criteria for an acceptable assay were met.

The groups that were treated with 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol showed no decrease in the ratio of polychromatic to normochromatic erythrocytes compared to the concurrent vehicle control group, indicating a lack of toxic effects of this test substance on erythropoiesis. The groups that were treated with cyclophosphamide and vinblastin showed expected decreases in the ratio of polychromatic to normochromatic erythrocytes compared to the vehicle control, demonstrating toxic effects on erythropoiesis.

It is concluded that 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol is not clastogenic or aneugenic in the bone marrow micronucleus test when sampled at 24 and 48 hours post dosing of male mice up to a dose of 2000 mg/kg (the maximum recommended dose in accordance with current regulatory guidelines) under the experimental conditions described in this report.


Short description of key information:
A Bacterial reverse mutation assay with 4 Salmonella strains, an in vitro chromosome aberration study and in vitro mammalian cell gene mutation test are available. All showed negative results, although in the chromosome aberration study an increase in polyploid cells was observed. A micronucleus test performed in vivo in mice indicated that the substance was not clastogenic or aneugenic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data do not lead to classification for genotoxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.