Phenyl methacrylate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Not mutagenic in the Salmonella typhimurium reverse mutation assay (OECD guideline 471; GLP)

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guideline/standards. GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

his (Salmonella strains), trp (E. coli strain)

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

first experiment: 0, 8, 10, 200, 1000, 5000 µg/plate
second experiment: 0, 312.5, 625, 1250, 2500, 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

without metabolic actication

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

other: 2-Aminoanthracene

Remarks:

with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: reduced bacterial growth

Evaluation criteria:

Although not given in the study report, according to OECD guideline 471 a test item is considered mutagenic if:
- a clear and dose-related increase in revertant number occurs
- a biologically relevant positive response for at least one dose group occurs: in TA 100 and E. coli uvrA number of revertants at least twice as high as in solvent control; TA 98, TA 1535, TA 1537 at least three times higher number of revertants as in solvent control

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

in TA100, TA1535, TA98

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY:
cytotoxicity (reduced bacterial growth) was observed in Salmonella strains TA100, TA1535 and TA98, but not in TA1537 and E. coli WP2uvrA-; however, the test item was tested up to limit concentrations

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

 

S9 mix	test item concentration [µg/plate]	mean number revertants/plate
		TA100	TA1535	E. coli WP2uvrA-	TA98	TA1537
without	0	110	15	35	20	13
	8	111	13	30	26	12
	10	116	14	31	22	12
	200	103	13	27	20	14
	1000	121	17	24	21	14
	5000	83*	12*	22	11*	13
	positive control	524	170	453	212	649
with	0	136	16	31	36	12
	8	135	15	30	33	12
	10	134	15	28	39	11
	200	137	17	28	33	13
	1000	134	13	30	34	13
	5000	133	15	33	33	14
	positive control	515	148	535	572	152

 

S9 mix	test item concentration [µg/plate]	mean number revertants/plate
		TA100	TA1535	E. coli WP2uvrA-	TA98	TA1537
without	0	103	11	15	17	8
	312.5	104	11	23	17	7
	625	104	12	19	18	9
	1250	116	11	17	20	8
	2500	88	11	16	4	6
	5000	53*	8*	19	5*	5
	positive control	508	141	458	210	497
with	0	125	14	18	30	13
	312.5	123	12	21	26	13
	625	118	12	21	33	13
	1250	122	13	23	18	14
	2500	123	12	18	24	13
	5000	105	15	18	22	13
	positive control	536	174	501	449	157

 

* cytotoxic, reduced bacterial growth

 

Conclusions:

Interpretation of results (migrated information):
negative

PHMA was not mutagenic in the bacterial reverse gene mutation assay when tested up to limit concentrations (5000 µg/plate).

Executive summary:

In a reverse gene mutation assay in bacteria similar to OECD guideline 471, S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 strains were exposed to PHMA (>99%) in DMSO at concentrations of 0, 8, 10, 200, 1000 and 5000 µg/plate in the first experiment and 0, 312.5, 625, 1250, 2500 and 5000 µg/plate in the second experiment in the presence and absence of mammalian metabolic activation (S9 mix).  PHMA was tested up to limit concentrations (5000 µg/plate).

Cytotoxicity (reduced bacterial growth) was observed in Salmonella strains TA100, TA1535 and TA98, but not in TA1537 and E. coli WP2uvrA-. The positive controls induced the appropriate responses in the corresponding strains. 

There was no evidence of induced mutant colonies over background. 

PHMA was not mutagenic in this bacterial reverse gene mutation assay when tested up to limit concentrations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

One reliable (RL=2), relevant and adequate study to assess the genotoxic potential of PHMA is available:

 

In a reverse gene mutation assay in bacteria similar to OECD guideline 471, S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 strains were exposed to PHMA (>99%) in DMSO at concentrations of 0, 8, 10, 200, 1000 and 5000 µg/plate in the first experiment and 0, 312.5, 625, 1250, 2500 and 5000 µg/plate in the second experiment in the presence and absence of mammalian metabolic activation (S9 mix).  PHMA was tested up to limit concentrations (5000 µg/plate).

Cytotoxicity (reduced bacterial growth) was observed in Salmonella strains TA100, TA1535 and TA98, but not in TA1537 and E. coli WP2uvrA-. The positive controls induced the appropriate responses in the corresponding strains. 

There was no evidence of induced mutant colonies over background. PHMA was not mutagenic in this bacterial reverse gene mutation assay when tested up to limit concentrations.

 

Thus, based on the available information, PHMA is not genotoxic. There are no data gaps for the endpoint genotoxicity. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

Justification for selection of genetic toxicity endpoint
OECD guideline study; GLP

Justification for classification or non-classification

Based on the available data PHMA does not need to be classified for mutagenicity according to the criteria given in regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.