3,3'-thiodi(propionic acid)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Only translated summary available, actual guideline not stated.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2003

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only summary available, guideline not stated

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-thiodi(propionic acid)

EC Number:

203-841-3

EC Name:

3,3'-thiodi(propionic acid)

Cas Number:

111-17-1

Molecular formula:

C6H10O4S

IUPAC Name:

3-[(2-carboxyethyl)sulfanyl]propanoic acid

Details on test material:

- Name of test material (as cited in study report): Thiodipropionic acid (TDPA), 3,3’-thiodipropionic acid; bis(2-carboxyethyl) sulfide; ß,ß-thiodipropionic acid; 3,3’-thiobis(propanoic acid); 4-thiaheptanedioic acid; diethyl sulfide 2,2’-dicarboxylic acid; thiodihydracrylic acid
- Analytical purity: no data

Method

Target gene:

Histidine operon for TA100, TA98,TA1535, TA1537, tryptophan operon for E. coli WP2 uvrA

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

156, 313, 625, 1250, 2500, 5000µg/mL

Vehicle / solvent:

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

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

with S9-mix Migrated to IUCLID6: 5µg/plate for TA 98, TA 100, TA 1537

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminanthrazene, 2µg/plate for TA 1535 and 10µg/plate for E. coli WP2 uvrA

Remarks:

with S9-mix

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, 0.01µg/plate for E. coli WP2 uvrA and TA 100 and 0.1µg/plate for TA 98

Remarks:

without S9-mix

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

without S9-mix Migrated to IUCLID6: 0.5µg/plate for TA 1535

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-methoxy-6-chloro-9-[3-(2-chloroethyl)-aminopropylamino] acridine·2HCl, 1µg/plate for TA 1537

Remarks:

without S9-mix

Details on test system and experimental conditions:

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

DURATION
- Preincubation period: 20min
- Exposure duration: 48h

NUMBER OF REPLICATIONS: 3

NUMBER OF CELLS EVALUATED: no data

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth by colonie count

Evaluation criteria:

The test was determined to be positive if the number of revertant colonies was nearly double or above that of the solvent control and this was found to be reproducible and to be dependant on the dosage of the test material.

Statistics:

Statistical methods were not used

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: no

RANGE-FINDING/SCREENING STUDIES:
The results of the dose-range finding test and main test did not find growth inhibition or deposition of precipitation/crystals in regards to the test strains at any concentration regardless of the strain type or whether or not there was metabolic activation.

Any other information on results incl. tables

Table 1: Maximum revertant counts

	Maximum number of revertants with
	solvent Control		positive control		Treatment (at dose level [µg/mL])
Strain	With S9	Without S9	With S9	Without S9	With S9	Without S9
TA 100	126	106	529	884	120 (2500)	118 (625)
TA 1535	8	13	91	1329	11 (313)	12 (313)
E. coli WP2	26	31	180	635	33 (313)	29 (1250)
TA 98	25	15	318	603	28 (313)	16 (1250)
TA 1537	12	15	93	2480	18 (313)	17 (625)

From the above results, it was determined that under these test conditions 3,3’-thiobispropanoic acid does not induce genetic mutations on bacteria.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative

Executive summary:

In a bacterial reverse mutation assay equivalent to OECD TG 471 S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A were exposed to 3,3’-thiobispropanoic acid at concentrations of 0 (control), 156, 313, 625, 1250, 2500, 5000 µg/mL in DMSO. The test was performed as plate incoporation and pre-incubation assay. Cytotoxicity was not observed. The test item did not induce revertants above background. Thus, 3,3’-thiobispropanoic acid is not mutagenic in this assay.