4-hydroxybenzophenone

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

4-HO-BP showed a suppression of bacterial growth without any P450 system, but no induction of umu gene expression (SOS/umu assay) was observed in Salmonella typhimurium TA1535/pSK1002. Human liver microsomes induced the bacterial cytotoxicity of this compound without any umu gene expression. On the other hand, with the addition of Escherichia coli membranes expressing recombinant human P450 2A6 and NADPH-cytochrome P450 reductase (NPR), 4-HO-BP showed umu gene expression (64 umu units/min/nmol) P450 2A6). Moderate activation of 4-HO-BP by P4501A1/NPR membranes, lA2/NPR membranes, or 1B 1/NPR membranes was also observed (Takemoto, Mutation Research 519, 2002, 199-204)

4-HO-BP showed genotoxic potential in the SOS/umu test (Zhao et al., Ecotoxicology and Environmental Safety 95, 2013, 241–246)

In an S. Typhimurium SOS/umuC genotoxicity assay, 4-OH-BP showed genotoxic activity at ≥125 mg mL^-1after metabolic activation, while in the absence of S9 no genotoxic effect was observed. It produced a dose dependent genotoxic response (Kotnik et al., Chemosphere 147, 2016, 114-123)

Ames test prediction with OASIS TIMES: negative. The calculated value was out of domain (structural fragment) and is therefore only a hint (see the attachement for detailed information).

OECD Toolbox: no alert found

Read-across data captured from published Benzophenone registration dossier:

Benzophenone was tested in several standard in vitro and in vivo studies performed according to recent guidelines. All of these studies gave no indications for a mutagenic/genotoxic potential. 

In vitro: 

Bacterial Reverse Mutation Assay (OECD Guideline 471): negative in S. typhimurium TA1535, TA1537, TA98 and TA100 both with and without metabolic activation (Mortelmans et al., 1986; NTP, 2006)

Bacterial Reverse Mutation Assay (OECD Guideline 471): negative in S. typhimurium TA98, TA100, TA1535, TA1537 and TA1538 both with and without metabolic activation (Seifried et al., 2006, Chem Res Toxicol 19, 627-644)

DNA damage and repair assay (unscheduled DNA synthesis in mammalian cells in vitro): negative in E. coli W3110 (Pol A+) and p3478 (Pol A-) both with and without metabolic activation (Fluck et al., 1976; Chem Biol Interactions 15, 219-231)

Mouse lymphoma assay (OECD Guideline 476): negative in L5178Y cells both with and without metabolic activation (Seifried et al., 2006, Chem Res Toxicol 19, 627-644)

In vivo: 

Micronucleus assay (OECD Guideline 474): negative (NTP, 2000) 

Micronucleus assay (OECD Guideline 474): negative (Abramsson-Zetterberg & Svensson, 2011, Toxicol Letters 201, 235–239)

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test and read-across data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 2015/1221.

In several SOS/umuC genotoxicity assays, 4 -OH-BP showed genotoxic activity after metabolic activation. Since this assay is only an indicator assay, this might explain the contrary results obtained in standard Ames and micronulceus assays with the read across substance benzophenone, which is partly metabolized to 4 -OH-BP. Benzophenone never showed any genotoxic activity in several test systems. Additionally, profiling performed with the OECD Toolbox gave no alerts for genotoxicity for 4 -OH-BP, and the prediction for mutagenicity was also negative based on OASIS Times, though it has to be considered, that the calculated result was out of domain (structural fragment).

As a result, due to the higher reliability of the standard tests performed with benzophenone, backed up by the negative QSAR predictions, 4 -OH-BP is not considered to be mutagenicity and no classification is justified.