3-(amidinothio)propionic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a reverse gene mutation assay in bacteria (Ames Test), no mutagenicity was observed with or without metabolic activation (BASF, 1996).

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:

1996-05-07 to 1996-05-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-induced rat liver S9 mix

Test concentrations with justification for top dose:

Experiment 1 and 2: 20, 100, 500, 2500, 5000 µg/plate

Vehicle / solvent:

DMSO
- Vehicle used: DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

with S9 mix (TA100, TA98, TA1537, TA 1535, WP2 uvrA)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-methyl-N-nitro-N-nitrosoguanidine

Remarks:

without S9 mix (TA100, TA1535)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylendiamine

Remarks:

without S9 mix (TA98)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without S9 mix (TA1537)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-methyl-N-nitro-N-nitrosoguanidine

Remarks:

without S9 mix (WP2 uvrA)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 - 72 hours

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: other: reduced background lawn

Evaluation criteria:

In general, a substance to be characterized as positive in the bacterial tests has to fulfill the following requirements:
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results.

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No test substance precipitation was found.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
No bacteriotoxic effect (reduced his or trp background growth) was observed.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Raw data

Experiment 1 (Standard Plate test)
Dose (µg/plate)	Mean number of revertant colonies/3 replicate plates with different strains of Salmonella typhimurium and Escherichia coli
	TA1535	TA1537	TA98	TA100	WP2 uvrA
	Results with S9
Spontaneous Reversion	20	7	35	120	49
Positive control	206	116	828	1064	176
20	16	7	38	112	44
100	18	7	29	110	46
500	20	7	27	93	47
2500	12	6	26	97	42
5000	13	6	30	79	41
	Results without S9
Spontaneous Reversion	20	7	23	106	44
Positive control	1430	658	1150	986	795
20	16	7	26	114	41
100	16	5	20	108	45
500	18	5	19	107	38
2500	19	7	20	118	44
5000	16	6	25	116	40
Experiment 2 (Pre-incubation test)
Dose (µg/plate)	Mean number of revertant colonies/3 replicate plates with different strains of Salmonella typhimurium and Escherichia coli
	TA1535	TA1537	TA98	TA100	WP2 uvrA
	Results with S9
Spontaneous Reversion	22	12	45	121	41
Positive control	137	111	675	782	208
20	20	13	48	113	35
100	19	9	45	124	39
500	20	11	41	118	32
2500	20	8	37	99	32
5000	19	7	39	107	35
	Results without S9
Spontaneous Reversion	21	6	32	116	44
Positive control	868	632	1097	1119	791
20	20	6	33	114	45
100	16	4	33	123	38
500	20	4	38	115	41
2500	16	4	33	117	40
5000	19	4	35	110	38

Conclusions:

Interpretation of results (migrated information):
negative

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

In a reverse mutation assay according to OECD guideline 471, strains (TA1535, TA1537, TA100, TA98 and WP2 uvr A) of S. typhimurium and Escherichia coli were exposed to the test substance at concentrations of 20, 100, 500, 2500 and 5000 µg/plate in the presence and absence of mammalian metabolic activation (BASF, 40M0133/964048, 1996). Each concentration was tested in triplicate.

The positive controls induced the appropriate responses in the corresponding strains. There was no evidence or a concentration related positive response of induced mutant colonies over background. The test substance was not mutagenic in the S. typhimurium strains TA1535, TA1537, TA100 and TA98 and the E. coli strain WP2 uvr A under the experimental conditions with or without metabolic activation.

Justification for selection of genetic toxicity endpoint
GLP and guideline compliant study.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes. As a result the substance does not need to be classified and labelled for mutagenic toxicity under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EU) No 2015/1221.