4,4'-sulphonyldiphenol

Specific investigations: other studies

Administrative data

Endpoint:

biochemical or cellular interactions

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Summary of methodologically similar, cell based screening assays; irrelevant for classification

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Measurement of estrogenic activity of chemicals for the development of new polymers

Author:

Hashimoto, Y.; Moriguchi, Y.; Oshima, H.; Kawaguchi, M.; Miyazaki, K.; Nakamura, M.

Year:

2001

Bibliographic source:

Toxicology in Vitro 15, 421-425

Reference 2

Reference Type:

publication

Title:

Estrogenic Activity of Dental Materials and Bisphenol-A Related Chemicals in vitro

Author:

Hashimoto, Y.; Nakamura, M.

Year:

2000

Bibliographic source:

Dental materials Journal, 19(3): 245-262

Reference 3

Reference Type:

publication

Title:

Acute Toxicity, Mutagenicity, and Estrogenicity of Bisphneol-A and Other Bisphenols

Author:

Chen, M.-Y.; Ike, M.; Fujita, M

Year:

2002

Bibliographic source:

Whiley Periodicals, Inc. Environ Toxicol 17: 80-86

Reference 4

Reference Type:

publication

Title:

Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivates using a GFP expression system

Author:

Kuruto-Niwa, R.; Nozawa, R.; Miyakoshi, T.; Shiozawa, T., Terao, Y.

Year:

2005

Bibliographic source:

Environmental Toxicology and Pharmacology 19, 121-130

Reference 5

Reference Type:

publication

Title:

Comparative Study of Endocrine-Disruping Activity of Bisphenol A and 19 Related Compounds

Author:

Kitamura, S.; Suzuki, T.; Sanoh, S.; Kohta, R.; Jinno, N.; Sugihara, K.; Yoshihara, S., Fujimoto, N.; Watanabe, H.; Ohta, S.

Year:

2005

Bibliographic source:

Toxicological Sciences 84, 249-259

Reference 6

Reference Type:

publication

Title:

Screening of high production volume chemicals for estrogen receptor binding activity (II) by the MultiCASE expert system

Author:

Klopman, G., Chakravarti, S. K.

Year:

2003

Bibliographic source:

Chemosphere 51, 461-468

Reference 7

Reference Type:

publication

Title:

Prediction of Endocrine Disruptors Based on a New Structure-Activity Relationship for Sex and Environmental Hormones Using Chemical Hardness Concept

Author:

Kobayashi, S.; Sugaya, T.; Sakata, N.; Uebayasi, M., Sameshima, K.; Tanaka, A.

Year:

2001

Bibliographic source:

Chem. Pharm. Bull. 49(6), 680-688

Reference 8

Reference Type:

publication

Title:

Weak estrogenic transcriptional activities of Bisphenol A and Bisphenol S

Author:

Grignard E., Lapenna S., Bremer S.

Year:

2012

Bibliographic source:

Toxicology in Vitro 26, 727–731

Reference 9

Reference Type:

publication

Title:

Relationship between the results of in vitro receptor binding assay to human estrogen receptor a and in vivo uterotrophic assay: Comparative study with 65 selected chemicals

Author:

Akahori Y., Nakai M., Yamasaki K., Takatsuki M., Shimohigashi Y., Ohtaki M.

Year:

2008

Bibliographic source:

Toxicology in Vitro 22, 225–231

Materials and methods

GLP compliance:

no

Type of method:

in vitro

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-sulphonyldiphenol

EC Number:

201-250-5

EC Name:

4,4'-sulphonyldiphenol

Cas Number:

80-09-1

Molecular formula:

C12H10O4S

IUPAC Name:

4-(4-hydroxybenzenesulfonyl)phenol

Results and discussion

Any other information on results incl. tables

Summary of available available literature data with respect to the endocrine modulating potential of 4,4'-sulphonyldiphenol:

Structural analysis:

Kobayashi et al. (2001) predicted endocrine modulation activities based on a structure-activity relationship for sex and environmental hormones using a chemical hardness concept. 4,4'-sulphonyldiphenol is predicted to be a soft acid, having potentially a female hormone activity based on this SAR system. A screening (Klopman and Chakravarti, 2003) of the structure of different chemicals for estrogen receptor binding activity by the MultiCASE expert system revealed a very low predicted binding capacity of 0.0006 for 4,4'-sulphonyldiphenol.

Cell free systems:

In a more specific system with regard to estrogenic activities (Hashimoto, 2000 and 2001), investigating the binding of different chemicals to a human recombinant estrogen receptor measured by fluorescence polarisation, the authors found a concentration dependent inhibition of the receptor ligand binding complex by 4,4'-sulphonyldiphenol. These effects were most cases weaker compared to other bisphenols.

In an additional in vitro receptor binding assay using recombinant human estrogen receptor alpha the binding affinities of 4,4'-sulphonyldiphenol and estrogen can be compared (Akahori et al., 2008). A significantly lower affinity to the estrogen receptor was identified for

4,4'-sulphonyldiphenol (logRBA -2.26) in comarioson to estrogen (logRBA 2).

Cellular systems:

Different tests investigating estrogenic activates in cellular systems are available. In 3 publications the estrogenic activity was measured with the yeast two-hybrid system. Hashimoto et al. (2000 and 2001) reported that 4,4'-sulphonyldiphenol showed no estrogenic activity without metabolic activation (S9 mix), but a slightly positive reaction with metabolic activation. The estrogenic activity in this system was however very low compared to other bisphenols. These findings are supported by an other study with the same test system (Chen, 2001).

Beside the tests in yeast, also data investigating 4,4'-sulphonyldiphenol in mammalian systems are available.

Kuruto-Niwa et al. (2004) showed that in comparison to Estradiol (EC50 = 9.67E-12) 4,4'-sulphonyldiphenol is way less active (EC50 = 1.75E-6) when measured in an ERE luciferase reporter assay in MCF7 cells.

These findings are confirmed by an other study with the same test system (Kitamura, 2005) showing an EC50 of 1.1 µM for 4,4'-sulphonyldiphenol and 8.6E-6 µM for Estrogen.

Kitamura et al. (2005) additionally indicated lower affinity of 4,4'-sulphonyldiphenol (IC50 = 17µM) compared to the antiandrogen flutamide (IC50 = 2.5 µM) when measuring the androgenic acitivity in NIN3T3 cells with a luciferase reporter assay.

Transactivation assays in two different cell lines reported by Grignard et al. (2012) indicate similar lower binding affinities for 4,4'-sulphonyldiphenol compared to Estradiol. The EC50 for 4,4'-sulphonyldiphenol in MELN cells was approximately 1000000 -fold lower compared to estradiol (4.24E-6 compared to 4.1E-11), the EC50 in BG1Luc4E2 cells was approximately 100000 -fold lower compared to estradiol (4.93E-6 compared to 1.24E-12).

 

Resumee:

No significant estrogenic activity of 4,4'-sulphonyldiphenol was identified in Yeast test systems.

Some estrogenic activity was identified in cell free systems with the estrogen receptor and some estrogenic and antiandogenic activity in mammalian cellular systems (reporter gene assay in MCF7 cells). Though the effect levels observed for 4,4'-sulphonyldiphenol in these test systems were always several orders of magnitude lower in comparison to natural or syntetical agonists.

Data interpretation for such assays is by definition based on upon whether or not the maximum response level induced by a test chemical equals or exceeds an agonist response equal to 10% of that induced by a maximally inducing concentration of the positive control 17beta estradiol, which is not fulfilled in the assays presented (e.g. OECD guideline 455).

The biological relevance of these results remains questionable and a correlation to predicted in vivo effects is not possible.

In vitro assays (e.g. Estrogen Receptor Transcriptional Activation Assays) are included in the second of five levels of an OECD conceptual framework for testing and assessment of potential endocrine disrupting chemicals. Each level is corresponding to a different level of biological complexity. By definition in vitro assays (e.g. TA assays) are screening assays and e.g. the influence of an agonist on an estrogen regulated reporter gene in vitro should not be directly extrapolated to the complex in vivo situation of estrogen regulation of cellular responses. As for a lot of chemicals with similar findings (positive effects in such screening assays) no effects (or effects at severely systemic toxic doses) were noted in well accepted state of the art in vivo tests according to OECD/EU guidelines.