Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Tests on bacteria

BPS did not induce gene mutations in several in vitro assays (OECD 471) performed on strains of Salmonella typhimurium and Escherichia coli.1 3 4 5

In a Chen et al. study on BPS, the umu-test was performed on Salmonella typhimurium with a negative result. The umu-test is based on the ability of the DNA-damaging agents to induce the umu operon on bacteria.

A DNA damaging chemical would induce umuC expression and consequently, lacZ expression (β-galactosidase activity).2

Fic et al., tested the mutagenic activity on Salmonella thyphimurium in a reverse mutation assay. BPS is not mutagenic.3

2,4'-sulfonyldiphenol CAS 5397-34-2 is considered suspected mutagenic (C&L ECHA Inventory), but no data are available.

Also, data on benzenesulfonic acid, 4-hydroxy-, sodium salt (1:1), CAS 825-90-1 and hydrotropes are not available.

Phenol is not genotoxic on bacteria.5

Reference:

1ECHA Registration Dossier CAS 80-09-1;

2Min-Yu Chen, Michihiko Ike and Masanori Fujita, Acute toxicity, mutagenicity, and estrogenicity of bisphenol-A and other bisphenols Environmental Toxicology Volume 17, Issue 1, pages 80–86, 2002;

3Anja FIC, Bojana ŽEGURA, Marija SOLLNER DOLENC, Metka FILIPIČ, And Lucija PETERLIN MAŠIČ, Mutagenicity And DNA Damage Of Bisphenol A And Its Structural Analogues in Hepg2 Cells. Arh Hig Rada Toksikol 2013;64:189 -200;

4SIDS INITIAL ASSESSMENT PROFILE, CAS 80-09-1, CoCAM 4, 16-18 April 2013;

5EPA, U.S. Environmental Protection Agency, Bisphenol A alternatives in thermal paper, Final Report, January 2014;

6Toxicological review of phenol. EPA, IRIS, 2002, EPA/635/R-02/006;

Mammalian cell/in vivo genotoxicity

BPS did not induce cell mutations in several in vitro assays according to OECD 476 performed CHO cell, both with and without S9 mix, and also a negative result with metabolic activation in an OECD 473 test (Chromosome Aberration Test).

In the same test, the substance induced structural chromosome aberration of CHL/IU cells and CHO cells without exogenous metabolic activation (OECD 473).

However, in an in vivo micronucleus assays in bone marrow cells of NMRI mice (OECD 474), BPS showed no micronucleus inducibility up to 2000 mg/kg bw (single or twice gavage dose) and it did not induce cytogenetic damage. BPS is therefore, considered to be non genotoxic in vivo.

The positive result in the in vitro assay on the OECD 473 test and negative result in the in vivo OECD 474 test suggest an equivocal response.1 2 3

In a Fic et al. study the DNA strand breaks ability by BPS was tested on HepG2 human cells. Those cells have been described in the OECD 487 in Vitro Mammalian Cell Micronucleus Test, although, they have not been used in validated studies.

BPS did not induce a significant increase in DNA strand breaks at the lowest dose, while after 24 hours of exposure DNA stand breaks was observed at the highest concentration, but with no dose-response relationship.4

It is possible to conclude that due to the BPS equivocal response on chromosome aberration and DNA strand breaks activity results, a moderate hazard concern should be considered.

2,4'-sulfonyldiphenol CAS 5397-34-2 is considered suspected mutagenic (C&L ECHA Inventory), but no data are available.

Also, data on benzenesulfonic acid, 4-hydroxy-, sodium salt (1:1), CAS 825-90-1 is not available.

The substance is the salified form of phenol sulfonic acid, which is a very acidic substance (comparable to sulphuric acid) and is almost completely ionised in watery environments, even at low pH.

Therefore, more realistic data on salified similar substances called hydrotropes, can be considered.

Toxicological properties of this substance can be helpful (in read across as well) to understand the toxicity of sodium sulphonated phenols, part of the intermediate DCB.

There are two in vivo mouse micronucleus studies for the related hydrotropes and both studies conclude the test substances were not mutagenic in these assays.5

Several inconclusive studies on phenol mutagenicity in vitro and in vivo are present, but the substance is already classified as mutagenic (Mutagen category 2, H341) in the Index VI of CLP Regulation 1272/2008/EC .6

Reference:

1ECHA Registration Dossier BPS CAS 80-09-1;

2SIDS INITIAL ASSESSMENT PROFILE, CAS 80-09-1, CoCAM 4, 16-18 April 2013;

3EPA, U.S. Environmental Protection Agency, Bisphenol A alternatives in thermal paper, Final Report, January 2014;

4Anja FIC, Bojana ŽEGURA, Marija SOLLNER DOLENC, Metka FILIPIČ, And Lucija PETERLIN MAŠIČ, Mutagenicity And DNA Damage Of Bisphenol A And Its Structural Analogues in Hepg2 Cells. Arh Hig Rada Toksikol 2013;64:189-200;

5ECHA Registration Dossier, Sodium xylenesulphonate, CAS 1300-72-7; ECHA Registration Dossier, Toluene sulphonic acid, CAS 104 -15 -4;

6Toxicological review of phenol. EPA, IRIS, 2002, EPA/635/R-02/006;


Short description of key information:
In vitro toxicity on bacteria: non genotoxic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Genetic toxicity

In order to classify the whole mixture for the genetic toxicity, the available classification and the results of the reported studies (vitro and in vivo) of every known component has been taken into account.

4,4'-sulfonyldiphenol (BPS): non classified

Benzenesulfonic acid, 4-hydroxy-, sodium salt (1:1)- hydrotropes, sodium xylenesulphonate (category approach): non classified

2,4'-sulfonyldiphenol: H341 (C&L ECHA Inventory)

Phenol: H341

Approximately 48% of the organic part of the intermediate under registration is composed of BPS.

Approximately 14% of the organic part of the mixture is the salified form of the phenol sulfonic acid, the benzenesulfonic acid, 4-hydroxy-, sodium salt (1:1). A category approach based on the hydrotropes can be taken into account for the classification of the whole intermediate mixture DCB. In fact, the properties of the salified form can be covered in read across with sodium xylene sulphonated (data available).

2,4'-sulfonyldiphenol is present at ca. 6% and it is considered suspected mutagenic (C&L ECHA Inventory).

Phenol, another suspected mutagen, is present in a concentration of 1.8% and for the evaluation of the genotoxic potential the presence between 0.1% to >=1% shall be taken into account.

In fact, according to the CLP Regulation 1272/2008/EC, 3.5 section, point 3.5.3.1, Table 3.5.2, generic concentration limits shall be used to determine if the mixture is considered to be or not a genotoxic (limit of => 1%).

Based on the information available, the intermediate DCB shall be classified as supected genotoxic, Category 2, H341.