2-Decyltetradecyl 3-[3-(2-decyltetradecoxy)-3-oxopropyl]sulfanylpropanoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1992-08-05, 1992-09-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (2-aminoanthracene was the only positive control compound used for reactions performed in the presence of metabolic activation).

Justification for type of information:

Thiobis Propanoic Acid Derivatives
The category covers thiiodipropionates that are symmetrically esterified by two linear aliphatic groups ranging in size from C10 to C24
The justification for the category is based on the expectation that the close structural similarity should result in properties that are either similar or follow a pattern that correlates with changes in the molecular weights of the compounds. The category members are high-molecular weight dithiopropionate esters that differ only in the chain length of the dialkyl ester functions and are expected to follow a regular pattern for all endpoints.
Based on the structures and molecularweights of the category members, as well as available data on category members, The predictive methods and extrapolation and interpolation of data within the category are acceptable. Data provided by other sources also demonstrate that these compounds generally have mammalian toxicities that are similar (e.g., acute oral LD 50, acute irritation thresholds, and genotoxicities) or follow a pattern that parallels changes in molecular weight (e.g., repeated-dose NOAEL).

The category is adequately supported based on chemical structure and available data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(2-aminoanthracene was used as only positive control with metabolic activation.)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: UKEMS

Deviations:

not applicable

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Didodecyl 3,3'-thiodipropionate

EC Number:

204-614-1

EC Name:

Didodecyl 3,3'-thiodipropionate

Cas Number:

123-28-4

Molecular formula:

C30H58O4S

IUPAC Name:

didodecyl 3,3'-sulfanediyldipropanoate

Details on test material:

- Name of test material (as cited in study report): Dilauryl Thiodipropionate
- Physical state: white powder
- Purity test date: 1992-06-01, 1992-06-11
- Lot/batch No.: 05/92
- Storage condition of test material: In the dark at room temperature

Method

Target gene:

his operon

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA102

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.

Test concentrations with justification for top dose:

1.6, 8, 40, 200, and 1000 µg/plate (experiment 1) and 62.5, 125, 250, 500, and 1000 µg/plate (experiment 2)

Vehicle / solvent:

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

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

2-nitrofluorene

Remarks:

strain TA98

Migrated to IUCLID6: 50.0 µg/plate in DMSO

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

sodium azide

Remarks:

strains TA100 and TA1535

Migrated to IUCLID6: 2.0 µg/plate in water

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

9-aminoacridine

Remarks:

strain TA1537

Migrated to IUCLID6: 50.0 µg/plate in DMSO

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

without metabolic activation

Positive control substance:

other: Glutaraldehyde (25.0 µg/plate in water)

Remarks:

strain TA102

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

with metabolic activation

Positive control substance:

other: 2-aminoanthracene 5.0 µg/plate in DMSO

Remarks:

at least applied in 1 strain

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation, experiment 1) and preincubation (with metabolic activation, experiment 2)

DURATION
- Preincubation period: 1 hours at 37 °C in nutrient broth (experiment 2)
- Exposure duration: 72 h at 37 °C (for both: in agar (plate incorporation) and preincubation test)

NUMBER OF REPLICATIONS: triplicate

DETERMINATION OF CYTOTOXICITY
- Method: The background lawn was inspected for signs of toxicity.

Evaluation criteria:

The assay was considered valid if the following criteria were met:
i) the mean negative control counts fell within the normal range
ii) the positive control chemicals induced clear increases in revertant numbers confirming discrimination between different strains, and an active S-9 preparation
iii) no more than 5% of the plates were lost through contamination or some other unforeseen event.
A test compound was considered to be mutagenic if:
i) the assay was valid
ii) Dunnett's test gave a significant response (p <0.01), and the data set showed a significant dose-correlation
iii) the positive responses described in (ii) were reproducible

Statistics:

For evaluation of test chemical and positive control data, the m-statistic was first calculated to check that the data were Poisson-distributed. Then, Dunnett's test was used to compare the counts of each dose with the control. The presence or otherwise of a dose response was then checked by linear regression analysis.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA102

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:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

presumably as the result of the increased exposure of the bacteria to the test agent due to the pre-incubation step.

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Yes, at 1000 µg/plate (experiment 1) and at 500 and 1000 µg/plate (experiment 2)

RANGE-FINDING/SCREENING STUDIES: Strain TA100 at 8, 40, 200, 1000, and 5000 µg/plate. No evidence of toxicity. Heavy precipitation of test agent was observed at concentrations of both 1000 and 5000 µg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA: Comparable

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: (experiment1)

Any other information on results incl. tables

Table 1: Revertants in S. typhimurium treated with the test substance, with and without metabolic activation (experiment 1):

Dose (µg/plate)	TA98		TA100		TA1535		TA1537		TA 102
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
0	22.2±5.7	17.2±6.1	115.2±6.4	124±3.2	21.8±2.9	26.6±4.3	17.8±2.1	13±3.5	232.6±21.1	305.4±39.5
1.6	27.7±5.1	24±7	105.7±6.7	119±29.5	26±1	29±1	15±2.6	10.3±3.1	298±50.7	362.3±7.8
8	29.7±5.9	21.3±7.4	95.3±9.5	113.7±9.1	23.7±10.4	18.7±7.6	14.3±4.6	9±2.6	265.3±11.7	317.3±33.6
40	25.3±6.7	21±6.1	113±2	124±23.8	17.7±2.5	23.7±1.2	16±5.3	11.7±3.5	267.7±39.7	333±28.6
200	29.0±2.6	22.7±8.4	108.7±11.9	99.3±24	21.7±1.2	28±4.4	15±1	11.3±3.5	283.3±26.5	316.7±15.3
1000	21.0±3.0	16.7±4.7	123.3±9.2	91±11	21.7±3.8	24±2.6	8.7±3.5	9.7±4	276±17.4	292±52.3
2-NF	1645.3±111.9	-	-	-	-	-	-	-	-	±
NaN3	-	-	810.3 ±57.4	-	463±57.7	-	-	-	-	-
AAC	-	-	-	-	-	-	425.7±9.1	-	-	-
AAN	-	1367.3±147	-	1800.3±249.7	-	195.7±4	-	-	-	-
GLU	-	-	-	-	-	-	-	-	477.7±45.8	-

(Mean ± SD)

  

2-NF: 2-nitrofluorene;

NaN3: sodium azide

GLU: glutaraldehyde

AAC: 9-aminoacridine

AAN: aminoanthracene

Table 2: Revertants in S. typhimurium, treated with the test substance, with and without metabolic activation (experiment 2):

Dose (µg/plate)

TA98

TA100

TA1535

TA1537

TA 102

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

-S9

+S9

0

29.4±5.0

28±4.5

111.6±12.7

103.6±10.8

22.2±2.8

21±1.6

15.4±3.8

13±2.2

319.2±48.9

357±19.4

62.5

34.7±1.2

21±1.7

109±13.5

83.7±5.1

21.3±1.2

19.7±3.2

19.3±2.5

18.3±0.6

271±43.4

316±16.9

125

36.7±7

28.7±6.1

113±10.5

87.3±10

16.3±3.5

11.3±4

16±0

13.7±2.1

222.3±11.9

311.3±13.4

250

36.3±5.5

34.3±1.2

102.7±3.1

90±28.3

21.3±5.7

22.3±3.1

17±2

14.3±3.1

237.3±27.6

351.3±11.4

500

19.3±9

24±4.6

90.3±1.5

70.7±2.1

15±5

21.3±3.8

15.3±2.1

16.3±4.5

292.3±29.8

162.7±11

1000

25.3±11.0

18.7±2.5

101±13.9

75.3±3.8

16.3±2.5

21±2.4

14.3±6.1

10.3±1.2

232.7±17.7

190.7±11

2-NF

1644±509.6

-

-

-

-

-

-

-

-

-

NaN3

-

-

773.3 ±75.1

-

479±49.4

-

-

-

-

-

AAC

-

-

-

-

-

-

643.3±227.7

-

-

-

AAN

-

2213.7±125.1

-

1451.7±38.1

-

-

-

-

-

-

GLU

-

-

-

-

-

-

-

-

715.3±89.4

-

(Mean ± SD)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic acitvation