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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial reverse mutation assay: negative with and without activation in S. typhimurium strains TA 98, TA100, TA1535, TA1537 and E. coli WP2uvrA (OECD TG 471) (Charles River, 2017).

Chromosome aberration: negative with and without metabolic activation in human lymphocytes (OECD 473) (RTC, 2018).

Mammalian mutagenicity: negative with and without metabolic activation in mouse lymphoma L5178Y in read-across from 2-methylpropane-2-thiol (OECD 476) (Hazelton, 1982).

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 May 2017 to 31 May 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: The vehicle of the test item was dimethyl sulfoxide.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was dissolved in dimethyl sulfoxide at a concentration of 50 mg/ml. Test item concentrations were used within 1 hour after preparation. Any residual volumes were discarded.
- Preliminary purification step (if any): No correction factor required.
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable

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:
Aroclor 1254 induced rat liver S9
Test concentrations with justification for top dose:
Selection of an adequate range of doses was based on a dose-range finding test with the strains TA100 and the WP2uvrA, both with and without S9-mix. Eight concentrations, 1.7, 5.4, 17, 52, 164, 512, 1600 and 5000 µg/plate were tested in triplicate. This experiment formed part of the main plate incorporation assay. The selected concentrations for the remaining strains in the plate incorporation assay with and for all strains in the preincubation assay were: 52, 164, 512, 1600 and 5000 μg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: based on solubility test
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA1535 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: ICR-191
Remarks:
TA1537 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA1537 and TA98 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
TA100 without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitroquinoline N-oxide
Remarks:
WP2uvrA without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
All strains with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation

ACTIVATION: . S9-mix contained per 10 ml: 30 mg NADP and 15.2 mg glucose-6-phosphate in 5.5 ml Milli-Q water; 2 ml 0.5 M sodium phosphate buffer pH 7.4; 1 ml 0.08 M MgCl2 solution; 1 ml 0.33 M KCl solution.

DURATION
- Plate incorporation: strains TA1535, TA1537 and TA98 were incubated in the dark at 37.0 ± 1.0°C for 48 ± 4 h. The preliminary toxicity study tested strains TA100 and WP2uvrA in the plate incorporation assay.
- Preincubation period: All strains were incubated for 30 minutes by 70 rpm at 37°C
- Exposure duration: at 37.0 ± 1.0°C for 48 ± 4 h

NUMBER OF REPLICATIONS: triplicate cultures

DETERMINATION OF CYTOTOXICITY
- Method: number of revertants; background lawn; presence of microcolonies
- Any supplementary information relevant to cytotoxicity: none

Rationale for test conditions:
Selection of an adequate range of doses was based on a dose-range finding test with the strains TA100 and the WP2uvrA, both with and without S9-mix. Eight concentrations, 1.7, 5.4, 17, 52, 164, 512, 1600 and 5000 µg/plate were tested in triplicate.
Evaluation criteria:
A test item is considered positive (mutagenic) in the test if:
a) The total number of revertants in tester strain TA100 or WP2uvrA is greater than two (2) times the concurrent control, or the total number of revertants in tester strains TA1535, TA1537 or TA98 is greater than three (3) times the concurrent control.
b) In case a repeat experiment is performed when a positive response is observed in one of the tester strains, the positive response should be reproducible in at least one follow up experiment.
Statistics:
Statistical significance
Key result
Species / strain:
other: S. typhimurium; TA98, TA100, TA1535, and TA1537 and E. coli WP2uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at all tester strain with and without metabolic activation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: not specified
- Effects of osmolality: not specified
- Water solubility: not specified
- Precipitation: Precipitation of the test item on the plates was not observed at the start or at the end of the incubation period.
- Definition of acceptable cells for analysis: not applicable

RANGE-FINDING/SCREENING STUDIES: Propane-1-thiol was initially tested in the tester strains TA100 and WP2uvrA as a dose-range finding test with concentrations of 1.7, 5.4, 17, 52, 164, 512, 1600 and 5000 µg/plate in the absence and presence of S9-mix. Based on the results of the dose-range finding test, the following dose-range was selected for the mutation assay with the tester strains, TA1535, TA1537 and TA98 in the absence and presence of S9-mix: 52, 164, 512, 1600 and 5000 μg/plate. The test item did not precipitate on the plates at this dose level. The bacterial background lawn was not reduced at any of the concentrations tested and no biologically relevant decrease in the number of revertants was observed.

HISTORICAL CONTROL DATA
- Positive historical control data: within the ranges of positive historical control data
- Negative (solvent/vehicle) historical control data: within the ranges of negative historical control data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: [complete, e.g. CBPI or RI in the case of the cytokinesis-block method; RICC, RPD or PI when cytokinesis block is not used]
- Other observations when applicable: [complete, e.g. confluency, apoptosis, necrosis, metaphase counting, frequency of binucleated cells]
Remarks on result:
other: preincubation

Table 1: Mean number of revertant colonies/3 replicate plates with different strains of Salmonella typhimurium and one Escherichia coli strain.

Concentration

μL/plate

TA 1535

TA 1537

TA 98

TA 100

WP2 uvrA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

Positive control

51

780

115

94

454

1357

786

816

655

133

Negative control

8

10

5

6

26

14

91

119

34

26

52

7

7

5

4

18

17

91

130

29

15

164

6

12

4

4

21

24

72

129

25

22

512

6

7

5

5

15

10

74

104

26

24

1600

MC

MC

3

3

14

9

63

69

22

13

5000

NP MC

NP MC

NP MC

NP MC

NP MC

NP MC

NP MC

NP MC

NP MC

NP MC

MC Microcolonies

NP No precipitate

Table 2: Positive controls, without metabolic activation

Strain

Chemical

Solvent

Concentration/plate Direct plate assay

Concentration/plate Pre-incubation assay

TA1535

sodium azide (SA)

(Sigma Aldrich Chemie, Steinheim, Germany)

Saline

5  µg

5  µg

TA1537

ICR-191 (Sigma)

DMSO

2.5 µg

 

TA1537

2-nitrofluorene (NF) (Sigma)

DMSO

 

15  µg

TA98

2-nitrofluorene (NF)

DMSO

10  µg

10  µg

TA100

methylmethanesulfonate (MMS) (Sigma)

DMSO

650  µg

650  µg

WP2uvrA

4-nitroquinoline N-oxide (4-NQO) (Sigma)

DMSO

10  µg

10 µg

Table 3: Positive controls, with metabolic activation

Strain

Chemical

Solvent

Concentration/plate Direct plate assay

Concentration/plate Pre-incubation assay

TA1535

2-aminoanthracene (2AA) (Sigma)

DMSO

2.5  µg

2.5  µg

TA1537

2-aminoanthracene (2AA)

DMSO

2.5  µg

2.5  µg

TA98

2-aminoanthracene (2AA)

DMSO

1  µg

1  µg

TA100

2-aminoanthracene (2AA)

DMSO

1  µg

5  µg

WP2uvrA

2-aminoanthracene (2AA)

DMSO

15 µg

15  µg

Conclusions:
Propane-1-thiol has been tested in a valid bacterial reverse mutation assay, according to OECD TG 471 (1997), and in compliance with GLP, using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and E. coli WP2uvrA. No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive and solvent controls were used and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start of experimental phase: 11 September 2017; End of experimental phase: 13 December 2017; Study completion: 12 April 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Version / remarks:
Adopted July 2016
Deviations:
no
GLP compliance:
yes
Type of assay:
other: in vitro mammalian chromosome aberration test
Species / strain / cell type:
lymphocytes: human
Metabolic activation:
with and without
Metabolic activation system:
S9 liver fraction from rats treated with phenobarbitone and betanaphtoflavone (mixed induction).
Test concentrations with justification for top dose:
The maximum dose level of 762 µg/mL (corresponding to 10 mM) and the lower dose levels of 508, 339, 226, 151, 100, 66.9, 44.6 and 29.7 µg/mL were used for all treatment series. For the continuous treatment in the absence of S9, the additional dose level of 19.8 µg/mL was included.
Vehicle / solvent:
Dimethyl sulfoxide
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
mitomycin C
Details on test system and experimental conditions:
Lymphocyte cultures were prepared using fresh venous blood drawn from healthy, non smoking individuals with no known recent exposures to genotoxic chemicals or radiation.
Treatment conditions:
3 hour treatment time in the absence of S9 metabolic activation and harvest time at 24 hours after beginning of treatment
3 hour treatment time in the presence of S9 metabolic activation and harvest time at 24 hours after beginning of treatment
24 hour treatment time in the absence S9 metabolic activation until harvest
Rationale for test conditions:
Lymphocytes in whole blood cultures were stimulated to divide by exposure to phytohaemagglutinin. After approximately 48 hours, a large proportion of the cells were completing their first division; at this point they were treated with the test item or control solutions. Post treatment mitosis were harvested for analysis at a time corresponding to approximately 1.5 cell cycle lengths (24 hours) to allow detection of chemicals which may cause cell cycle delays.
Evaluation criteria:
The test item is considered as clearly positive if the following criteria are met:
Any dose level shows a statistically significant increase in aberration-bearing cells (excluding gaps)
The incidence of cells bearing aberrations is outside the normal distribution of historical control values
The increase of cells bearing aberration is dose-related when evaluated with an appropriate trend test
The test item is considered clearly negative in this assay, if none of the above criteria is met.
Statistics:
Fisher’s Exact Test was used to compare the number of cells bearing aberrations (assumed to be Poisson distributed) in control and treated cultures.
Bonferroni’s corrections were applied for multiple comparisons. The analysis was performed using sets of data either including or excluding gaps.
Cochran-Armitage trend test (one-sided) was performed to aid determination of concentration response relationship.
Key result
Species / strain:
lymphocytes: human
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid

Solubility: no opacity nor precipitation of the medium was observed at the beginning or end of treatment, in the absence or presence of S9 metabolism, at any dose level, in any treatment series.

Effects on pH and osmolality: no remarkable variation of pH over the concurrent control was observed at any dose level or treatment conditions.

Cytotoxicity results: Following the short term treatment in the absence of S9 metabolism, severe toxicity was observed at the highest dose level of 762 µg/mL, where few metaphases were recovered, marked toxicity was observed at the lower dose levels of 508 and 339 µg/mL reducing the mitotic index to 36% and 40% of the concurrent negative control, respectively. Moderate toxicity was observed at the dose levels of 226, 151, 100 and 66.9 µg/mL where the relative mitotic index ranged between 46% and 55%. Mild and no remarkable toxicity was observed at the two lower dose levels of 44.6 and 29.7 µg/mL. Following the short termtreatment in the presence of S9 metabolsism, severe toxicity was observed at the highest dose level of 762 µg/mL, where few metaphases were recovered. Marked toxicity was observed at the lower dose levels of 508, 339 and 226 µg/mL reducing the mitotic index between 20% and 32% of the concurrent negative control. Moderate to mild cytotoxicity was observed over the remaining dose range.

Following the continuous treatment in the absence of S9, severe toxicity was observed at the highest dose levels of 762, 508 and 339 µg/mL, where no methaphases or few metaphases were recovered. Moderate toxicity was seen at the dose levels of 226 and 151 µg/mL (relative mitotic index 52% and 50% respectively). Mild to no cytotoxicity was seen over the remaining dose range.

Dose levels selected for scoring:

 3 hour treatment -S9 Mix  226, 100 and 44.6 µg/mL
 3 hour treatment +S9 Mix  151, 66.9 and 29.7 µg/mL
 24 hour treatment -S9 Mix  226, 100 and 44.6 µg/mL

Results show that the proportion of cells with structural aberrations (excluding gaps) in vehicle control cultures fell within the normal range based on historical control data (confidence interval: mean value ± 2 standard deviations). Adequate number of cells (at least 300 at each test point) and test item concentrations were analysable. The positive control items, Mitomycin-C and Cyclophosphamide, induced statistically significant increases in the incidence of cells with structural aberrations compared with the concurrent

negative control and the responses were compatible with the historical control range. The study was accepted as valid.

Test item treatments did not induce statistically significant increases in aberration-bearing cells and no statistically significant dose-effect relationship was indicated. The incidences of cells bearing aberrations were within the distribution of the historical data for negative

controls.

Conclusions:
Based on the results obtained, it is concluded that 1-PROPANETHIOL does not induce chromosome aberrations in human lymphocytes after in vitro treatment, under the reported experimental conditions.
Executive summary:

The test item 1-PROPANETHIOL was assayed for the ability to induce chromosomal damage in cultured human lymphocytes, following in vitro treatment in the absence and presence of S9 metabolic activation. Three treatment series were included in the study. A short termtreatment was performed where the cells were treated for 3 hours in the presence and absence of S9 metabolism. The harvest time of 24 hours corresponding to approximately 1.5 cell cycle was used. A long term (continuous) treatment was also performed in the absence of S9 metabolism until harvest at 24 hours.

Solutions of the test item were prepared in dimethylsulfoxide (DMSO).

The maximum dose level of 762 µg/mL (corresponding to 10 mM) and the lower dose levels of 508, 339, 226, 151, 100, 66.9, 44.6 and 29.7 µg/mL were used for all treatment series. For the continuous treatment in the absence of S9, the additional dose level of 19.8 µg/mL was included. Appropriate negative and positive controls were included. Two replicate cell cultures were prepared at each test point.

For all treatment series, dose levels were selected for the scoring of chromosomal aberrations on the basis of the cytotoxicity of the test item treatments (as determined by the reduction in mitotic index).

Dose levels selected for scoring were:

 S9

 Treatment time

(hours)

 Harvest time

(hours)

 

Dose level

(µg/mL)

 

Relative mitotic

index (%)

 -

 3

 24

 226, 100 and 44.6

 46, 55 and 75

 +

 3

 24

 151, 66.9 and 29.7

 46, 55 and 61

 -

 24

 24

 226, 100 and 44.6

 52, 63 and 79

 

For each culture, 150 well spread metaphases were scored to assess the frequency of aberrant cells.

Following treatment with the test item, no statistically significant increase in the incidence of cells bearing aberrations, including or excluding gaps, was observed at any dose level and treatment condition.

No dose related increase of the incidence of cells bearing aberration was observed and all the incidences were within the distribution of the historical data for negative controls.

Statistically significant increases in the incidence of cells bearing aberrations (both including and excluding gaps) were seen following positive control treatments with Mitomycin-C and Cyclophosphamide, indicating the correct functioning of the assay system.

It is concluded that 1-PROPANETHIOL does not induce chromosomal aberrations in human lymphocytes after in vitro treatment, under the reported experimental conditions.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
This study is classified as reliable with restrictions because it is comparable to the guideline with acceptable restrictions.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
only 0.5E06 cells were plated for selection of mutants, individual culture data were not provided, and large vs small colonies were not determined
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
L5178Y mouse lymphoma cells subline 3.7.2C
Metabolic activation:
with and without
Metabolic activation system:
S-9 liver microsomes from male Sprague Dawley rats treated with a single intraperitoneal injection of Aroclor 1254 at a dose of 500 mg/kg 5 days before sacrifice.
Test concentrations with justification for top dose:
61, 90, 135.0, 202, 300, 449, 670, or 1000 mg/ml. 1000 mg/ml limit of solubility.
Vehicle / solvent:
DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Ethylmethanesulfonate (EMS, 620 µg/ml) without metabolic activation and 3-methylcholanthrene (3-MCA, 3 µg/ml) with metabolic activation
Details on test system and experimental conditions:
TOXICITY EVALUATION:
The test compound dose levels were determined by a preliminary multidose range-finding study with the highest dose tested being selected to give approximately 50 - 90% inhibition of suspension cell growth depending on the solubility of the compound. T-Butyl mercaptan solubilized at approximately 100 mg/ml in dimethylsulfoxide. One-tenth ml of each test substance concentration and the solvent were added to 50 ml tubes containing 6.0 x 10(6) TK+/- cells in 10 ml F10P. Cells were exposed to the chemical for 4 hrs, washed, resuspended in 20 ml F10P and incubated for 2 days. After the first and second day of incubation, the cell counts and viability were determined by counting a sample of the cells using a hemocytometer in the presence of trypan blue. Following the first day of incubation, the viable cell count was adjusted to 3.0 x 10(5) cells/ml. Based on the cell counts, the relative toxicity of the chemical compared to the solvent control was determined. The maximum dose selected for the mutagenicity test was 1000 ug/ml because it represented the limits of solubility of the test material.

MUTAGENICITY ASSAY:
Each test concentration was prepared to contain the test dose in 0.1 ml volumes. Six million precleansed TK+/- cells in 6 ml of F10P were added to centrifuge tubes. An additional 4 ml of the S-9 mix were added to half of the tubes. Immediately thereafter, 0.1 ml of the 100x concentrations of the test chemical dilutions or the positive controls, and 0.1 ml of the solvent were added to the appropriate tubes. Each tube was mixed, gassed with a mixture of C02 and air, and incubated at 37± 0.5°C on a revolving roller drum for 4 hours. Following this incubation the tubes were centrifuged and the treatment solutions decanted. The cells were washed twice with F10P and resuspended in 20 ml F10P after the second wash. The tube cultures were then gassed and reincubated for a 2 day expression time. The cell cultures were readjusted to 3.0 x 10(5) cells/ml as necessary. At the end of the expression period, a sample of each of the cultures was centrifuged and the cells resuspended at 500,000 viable cells/ml in F10P. The concentrated cells were serially diluted and appropriate dilutions were plated in triplicate in cloning medium with and without TFT. Approximately 500,000 cells were plated on each of 3 selective medium plates containing 2 ug/ml TFT, and 100 cells were cloned on each of 3 non-selective plates for each test concentration and a control tube. The plates were incubated for 10-14 days. The mutant colonies (TK+/-) were counted on the selective TFT containing plates and the survivors (TK+/- and TK-/-) were counted on the non-selective medium plates. The daily cell counts were made using a microscope and hemocytometer; and the colony counts were obtained with an electronic colony counter. The number of mutants in the test and control groups was compared and their mutation frequencies determined, along with a determination of relative total survival based on the suspension cell growth and cloning efficiency.
Evaluation criteria:
Test substance considered positive if a dose-related response at two or more test concentrations (in the absence of severe toxicity) is at least two to three-fold higher than the mutation frequency of the solvent control.
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Without metabolic activation: Survival = 10.6% at 670 µg/ml and 3.0% at 1000 µg/ml; with metabolic activation: Survival = 10.9% at 1000 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
Exposure to eight graded doses of the test material in the presence of metabolic activation did not increase the induction of forward mutations in L5178Y mouse lymphoma cells at the T/K locus. Exposure to the 202 and 1000 µg/ml dose levels of the test material in the absence of metabolic activation increased the induction of forward mutations in L5178Y mouse lymphoma cells at the T/K locus. Under these conditions, t-butyl mercaptan did exhibit a positive response. However, the induction of increases in mutant frequency was not dose responsive and, thus, did not satisfy the stated criteria for a positive response; therefore, t-buty mercaptan was not mutagenic under the conditions of this assay.
Treatment without S-9
µg/ml
%Survival
MF
Fold Increase
DMSO
--
100
3.4
1.0
EMS
620
78.0
14.8
4.4
TBM
1000
3.0
7.6
2.2
670
10.6
6.2
1.8
449
60.0
5.3
1.6
300
56.1
4.2
1.2
202
93.5
7.4
2.2
135
94.9
3.8
1.1
90
126.8
2.3
0.7
61
100.1
3.2
0.9
MF - mutation frequency [x10e-5]
Conclusions:
negative
Executive summary:

An In vitro Mammalian Cell Gene Mutation (mouse lymphoma) assay was performed with 2 -methylpropane-2-thiol in a study similar to OECD Guideline 476. L5178Y TK (+/-) mouse lymphoma cells were exposed to eight concentrations of t-butyl mercaptan (61 to 10,000 µg/ml) in the presence and absence of a metabolic activation system. 2 -methylpropane-2-thiol did not result in mutagenic responses in this assay. Positive controls provided the appropriate responses. 

This study received a Klimisch Score of 2 and is classified as reliable with restrictions because it is comparable to the guideline with acceptable restrictions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Propane-1-thiol has been tested in a valid bacterial reverse mutation assay, according to OECD TG 471 (1997), and in compliance with GLP, using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and E. coli WP2uvrA (Charles River, 2017). No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive and solvent controls were used and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Propane-1-thiol has been tested for ability to cause chromosome aberrations in human lymphocytes according to OECD TG 473 and in compliance with GLP (RTC, 2018). No increase in the number of cells with aberrations was observed either with or without metabolic activation in human lymphocytes when tested up to cytotoxic concentration. Appropriate solvent and positive controls were included and gave the expected results.

There were no mammalian mutagenicity data for the registered substance propane-1-thiol. Therefore, data were read-across from the structurally analogous substance 2-methylpropane-2-thiol. Propane-1-thiol and 2-methylpropane-2-thiol are characterised by an SH functional group with an aliphatic carbon chain. The substances vary in molecular weight and in having straight and branched aliphatic carbon chains respectively, and in the position of the thiol group but the similarities of the physicochemical and toxicity properties are apparent.

2 -Methylpropane-2-thiol (CAS 75-66-1) has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 476 and in compliance with GLP (Hazelton, 1982). No test-substance induced increase in the number of mutations was observed when tested up to cytotoxic concentration. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study.

Justification for classification or non-classification

Based on the available data for propane-1-thiol and 2-methylpropane-2-thiol, no classification for genetic toxicity is required for propane-1-thiol according to Regulation (EC) No 1272/2008.