Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro

Bacterial reverse mutation assay

Four studies are available to address this endpoint, one key and three supporting. The key study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997). The supporting studies were all awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

The key study was conducted in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A in accordance with OECD 471 under GLP conditions (BioReliance, 2002).

Bacteria were exposed to the test material at concentrations up to 5000 µg/plate in DMSO both with and without S9 metabolic activation.

Under the conditions of this study, BPA-DA did not cause a positive response in either the presence or absence of Aroclor induced rat liver S9 and is therefore non-mutagenic.

 

In the first supporting study, S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and TA1538 were exposed to the test material in DMSO at concentrations up to 30 mg/plate both with and without metabolic activation in accordance with the US EPA Health Effects Test Guidelines under GLP conditions (Bushy Run Research Center, 1988).

The test substance did not exhibit mutagenic activity in any of the assays and was considered not mutagenic under these test conditions.

 

In the second supporting study, S. typhimurium TA1535, TA1537, TA1538, TA98 and TA 100 were exposed to the test material in DMSO at concentrations up to 10 000 µg/plate both with and without metabolic activation in accordance with the method of Ames et al. under GLP conditions (Litton Bionetics, Inc., 1981).

The test substance did not exhibit mutagenic activity in any of the assays and was considered not mutagenic under these test conditions.

 

In the third supporting study, S. typhimurium TA1535, TA1537, TA1538, TA98 and TA 100 and Saccharomyces cerevisiae (Strain D4) were exposed to the test material in DMSO at concentrations up to 500 µg/plate both with and without metabolic activation in accordance with the method of Ames et al. (Litton Bionetics, Inc., 1977).

The test substance did not exhibit mutagenic activity in any of the assays and was considered not mutagenic under these test conditions.

 

Chromosome aberration test

The key study was conducted in Chinese hamster Ovary (CHO) cells in accordance with OECD 473 under GLP conditions (BioReliance, 2004). The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

CHO cells were exposed to the test material in DMSO at concentrations up to 1500 µg/mL without metabolic activation and up to 750 µg/mL with metabolic activation.

Under the conditions of the assay, BPA-DA was concluded to be negative for the induction of structural and numerical chromosome aberrations in CHO cells.

 

Mammalian cell gene mutation assay

The key study was conducted in mouse lymphoma L5178Y cells in accordance with OECD 476 under GLP conditions (BioReliance, 2004). The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Mouse lymphoma L5178Y cells were exposed to the test material in DMSO at concentrations up to 150 µg/mL with metabolic activation (4-hour exposure) and up to 125 µg/mL without metabolic activation (4- and 24-hour exposure).

Under the conditions of this study, the mutagenicity of BPA-DA was concluded to be negative with and without metabolic activation.

 

In vivo

Micronucleus assay

The key study was conducted in ICR mice in accordance with OECD 474 under GLP conditions (BioReliance, 2003). The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Male and female ICR mice were dosed via the intraperitoneal route with test material concentrations of 200, 400 or 800 mg/kg body weight in corn oil.

No mortality was observed. Clinical signs following dose administration included: piloerection in males and females at all doses and lethargy in males at 400 mg/kg and in males and females at 800 mg/kg. All other animals treated with control articles appeared normal during the course of the study.

Bone marrow cells (polychromatic erythrocytes, PCEs and normochromatic erythrocytes, NCEs), collected 24 and 48 hours after treatment were examined microscopically for presence of micronuclei (MPCEs or MNCEs). Reductions of 15, 37 and 56 % in the ratio of polychromatic erythrocytes to total erythrocytes were observed at 800 mg/kg in female group 24 hours post-dose and in male and female group 48 hours post-dose, respectively. These reductions demonstrate that there was bioavailability of BPA-DA to the bone marrow target tissue.

Under the conditions of the assay, BPA-DA did not induce a significant increase in the incidence of micronucleated polychromatic erythrocytes in bone marrow. Therefore, it was concluded to be negative in the micronucleus test.


Justification for selection of genetic toxicity endpoint
No single study is selected as key on the basis that the different studies address different aspects of genetic toxicity and the data are therefore all considered to be key.

Short description of key information:
IN VITRO
A bacterial reverse mutation assay conducted in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A with and without metabolic activation in accordance with OECD 471 concluded that BPA-DA is non-mutagenic.
An in vitro mammalian chromosome aberration test conducted in Chinese hamster Ovary (CHO) cells with and without metabolic activation in accordance with OECD 473 concluded that BPA-DA is non-mutagenic.
An in vitro mammalian cell gene mutation assay conducted in mouse lymphoma L5178Y cells with and without metabolic activation in accordance with OECD 476 concluded that BPA-DA is non-mutagenic.

IN VIVO
An in vivo micronucleus assay conducted in ICR mice in accordance with OECD 474 concluded that BPA-DA is non-mutagenic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to mutagenicity.