Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

There are conclusive but not suffcient data for the classification of substance S-allyl O-pentyl dithiocarbonate with regard to mutagenicity/genetic toxicity. It is concluded that the substance S-allyl O-pentyl dithiocarbonate does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
only 4 bacterial strains tested
Qualifier:
according to
Guideline:
EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
Deviations:
no
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix- rat liver, Aroclor 1254 administered
Test concentrations with justification for top dose:
0.005%, 0.01%, 0.025%, 0.05%, 0.1% v/v
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: none
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
Remarks:
no solvent/vehicle used
Positive controls:
yes
Positive control substance:
other: in the abscence and presence of metabolic activation: 2-aminoanthracene (TA1535), benzo[alpha]pyrene (TA1537, TA100, TA98); in the abscence of metabolic activation: sodium azide (TA1535, TA100), 9-aminoacridine (TA1537), 2-nitrofluorene (TA98);
Remarks:
dicloromethane in a vapour phase (7.5% v/v) was included in each test without metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

NUMBER OF REPLICATIONS:3/ treatment

DETERMINATION OF CYTOTOXICITY

- Method: abscence or thinning of the background lawn of non-revertant colonies

EXPOSURE TO CS2:
Sets of solidified plates were placed, with lids removed, in stainless steel racks, designed to keep the plates separate and permit atmospheric circulation, inside stainless steel vessels. These vessels were then sealed and partially evacuated. Calculated volumes of carbon disulphide liquid were injected into the vessels via a septum and allowed to vaporize, producing atmospheres containing carbon disulphide at the nominal concentrations
mentioned above.Sterile air was admitted to the vessels in order to equilibrate the contents to atmospheric pressure, and the vessels with their contents were incubated at 37°C for 48 hours. After removal from the vessels, the plates were incubated for a further day in order to permit revertant
colonies to grow to a size large enough to be scored.
Evaluation criteria:
number of revertants/plate
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:
other: yes, only at the highest concentration
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Carbon disulphide was examined for its mutagenic activity in four histidine-dependent auxotrophs ofSalmonella typhimurium, strains TA98, TA100, TA1535, TA1537. Agar plates, seeded with the tester strains, were exposed to the test material in vapour phase, in the abscence and presence of metabolic activation, in the following nominal concentrations: 0.005%, 0.01%, 0.025%, 0.05% and 0.1% v/v (nominal). These concentrations were selected following preliminary toxicity tests in strain TA 98. Carbon disulphide did not exhibit any mutagenic activity under the conditions of this test. No increases in revertants were obtained in any of the four tester strains following exposure to carbon disulphide at the concentrations tested. Inhibition of bacterial growth, observed as thinning of the background lawn of non-revertant cells and reduction in revertant colony numbers, occurred in all strains with carbon disulphide at a nominal concentration of 0.1 % v/v. The positive and negative controls were valid.
The study was performed according to the OECD Guidelines for Testing of Chemicals No. 471 (1983) and US EPA (TSCA) Guideline § 798.5265 (1985, amended 1987).
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results :negative

No mutagenic activity of CS2 detected.Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Executive summary:

Carbon disulphide was examined for its mutagenic activity in four histidine-dependent auxotrophs of Salmonella typhimurium, strains TA98, TA100, TA1535, TA1537. Agar plates, seeded with the tester strains, were exposed to the test material in vapour phase, in the abscence and presence of metabolic activation, in the following nominal concentrations: 0.005%, 0.01%, 0.025%, 0.05% and 0.1% v/v (nominal). These concentrations were selected following preliminary toxicity tests in strain TA 98. Carbon disulphide did not exhibit any mutagenic activity under the conditions of this test. No increases in revertants were obtained in any of the four tester strains following exposure to carbon disulphide at the concentrations tested. Inhibition of bacterial growth, observed as thinning of the background lawn of non-revertant cells and reduction in revertant colony numbers, occurred in all strains with carbon disulphide at a nominal concentration of 0.1 % v/v. The positive and negative controls were valid. The study was performed according to the OECD Guidelines for Testing of Chemicals No. 471 (1983) and US EPA (TSCA) Guideline § 798.5265 (1985, amended 1987).

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
At least duplicate cultures must be used for each experimental point. Only one harvest time was used.
Qualifier:
according to
Guideline:
EPA OPP 84-2
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
other: Chinese hamster overy cells
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
3.1, 12.5, 25 ng/ml (without S-9 mix)
125, 500, 1000 ng/ml (with S-9 mix)
Vehicle / solvent:
DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Mitomycin C, Cyclophosphamide
Species / strain:
other: Chinese hamster overy cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

 

Dose level [ng/mL]

No. of aberrant cells [%]

Dose level [ng/mL]

No. of aberrant cells [%]

With MA

Without MA

Exc. gaps

Inc. gaps

Exc. gaps

Inc. gaps

125

4.5

4.5

3.1

2.0

2.0

500

3.5

4.5

12.5

2.5

2.5

1000

3.5

3.5

25.0

4.0

4.0

Solvent

4.25

4.75

Solvent

2.25

2.25

Positive control

38.5

38.5

Positive control

29.0

29.0

 

Conclusions:
Interpretation of results :negative

No mutagenic activity of Ziram detected.Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, pentan-1-ol/Amyl alcohol need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Qualifier:
according to
Guideline:
other: according to: Ames, B.N., McCann, J. and Yamasaki, F. 1975. Methods for detecting carcinogens and mutagens with Salmonella/mammalian-microsome mutagenicity test.
Principles of method if other than guideline:
Method: other:Primary amyl acetate was dissolved in absolute ethanol to a concentration of 20 ul/ml; all dilutions were made on the day of testing. A preliminary toxicity test was performed to determine the level of cytotoxicity of the test material to the tester strains. Ten doses, from 0.001 to 50 ul per plate were tested. The top four doses, 50, 10, 3 and 1 ul/plate exhibited cytotoxicity. Based on these results, mutagenicity testing was performed with 5 doses of 1.0, 0.3, 0.1, 0.03 and 0.01 ul/plate. All doses were tested in triplicate, in the presence and absence of metabolic activation, in 5 tester strains. Arochlor 1254-induced rat liver homogenate (S9) was prepared fresh on the day of testing from male Sprague Dawley rats. For tests with metabolic activation, 0.5 ml of S9 mix containing 50 ul S9 was added per plate.
Solvent and positive controls were run concurrently with the test material. For all tests, the solvent control was ethanol (50 ul/plate). The positive control used for all tester strains in tests with metabolic activation was 2-aminoanthracene (10 ug/plate). The positive controls used for each tester strain in tests without metabolic activation were as follows:
TA98, TA1538: 4-nitro-o-phenylenediame (10 ug/plate)
TA100, TA1535: sodium azide (10 ug/plate)
TA 1537: 9-aminoacridine (60 ug/plate).

A compound is considered a bacterial mutagen if the number of revertant colonies is at least twice the solvent control for at least one dose level and there is evidence of a dose-related increase in the number of revertant colonies.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
His +/-
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 97
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver, 5-30%)
Test concentrations with justification for top dose:
0, 33, 100, 333, 1000, 3333, 6666 and 10000 µg/plate
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 1342 The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97), 4-nitro-o-phenylenediamine (TA98). The positive control with S9 mix was 2- aminoanthracene in all strains
Details on test system and experimental conditions:
- The test substance was incubated with the Salmonella typhimurium tester strains TA97, TA98, TA100, TA1537, and TA1535 either in buffer or S9 mix for 20 minutes at 37° C.
- Top agar supplemented with L-histidine and d-biotin was added, and the contents of the tubes were mixed and poured onto the surfaces of minimal glucose agar plates.
- Histidine-dependent mutant colonies arising on these plates were counted following incubation for 2 days at 37° C.
Evaluation criteria:
- A positive response was defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination.
- An equivocal response was defined as an increase in revertants that was not dose related, was not reproducible, or was not of sufficient magnitude to support a determination of mutagenicity.
- A negative response was obtained when no increase in revertant colonies was observed following chemical treatment.
- There was no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.
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:
cytotoxicity
Remarks:
dose units starting from 6666 were generally slightly toxic to toxic for all strains tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
dose units starting from 6666 were generally slightly toxic to toxic for all strains tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Results:

Strain TA1535

Dose

No Activation

No Activation

10% HLI

30% HLI

10% RLI

30% RLI

 

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

 

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

 

0     

19

4.5

21

0.3

11

1.7

7

1.8

8

0.7

12

0

33     

 

 

22

3.7

 

 

 

 

 

 

 

 

100     

20

2

17

1.8

12

3

13

1.5

10

0.7

12

0.3

333     

19

2.6

21

4.5

6

0.9

9

1.8

10

0.9

15

1

1000     

19

2.7

16

0.9

7

2.3

9

0.3

8

1.5

11

1.5

3333     

21

1.5

17

1

5

1.9

7

1.2

11

2.2

12

1.9

6666     

 

 

 

 

 

 

 

 

10

2.8

 

 

10000     

4s

1.7

 

 

6

1.8

7

2

 

 

8

0

Positive Control

423

19.6

498

23.3

263

28.7

375

13

204

7.5

224

10.2

 

Strain TA 100

Dose

No Activation

No Activation

10% HLI

30% HLI

10% RLI

30% RLI

 

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

 

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

 

0     

139

8.8

115

4.3

135

15.3

163

1.7

107

4.9

165

5.8

33     

 

 

122

3.8

 

 

 

 

 

 

 

 

100     

136

12

120

9.1

141

3.8

166

15.5

126

11

142

6.3

333     

120

7.6

125

7.8

140

7.7

175

2.7

113

5.5

173

2.4

1000     

116

4.2

116

6.4

123

6.8

169

6.1

116

10

176

12.2

3333     

119

7.9

96

12.1

130

5.7

141

7

120

2.7

178

9.2

6666     

t

 

 

 

109

13.9

126

5.8

96

6.8

126s

16.2

Positive Control

604

4

464

24.9

822

12.8

529

14.2

557

24.5

478

14.7

 

Strain TA 97

Dose

No Activation

No Activation

10% HLI

30% HLI

5% RLI

10% RLI

10% RLI

30% RLI

 

(Negative)

(Equivocal)

(Negative)

(Negative)

(Negative)

(Equivocal)

(Negative)

(Equivocal)

 

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

 

0     

136

10.5

111

7.4

152

9.2

165

6.4

200

16.5

111

6.5

186

5.4

153

2.7

33     

 

 

147

13.8

 

 

 

 

 

 

 

 

 

 

 

 

100     

159

12.3

136

2.2

150

12.9

160

17.2

186

6.9

165

0.9

211

7

189

6.8

333     

163

6.7

157

9.5

161

3.3

179

8.3

197

5.5

183

5.4

199

6.5

191

3.2

1000     

154

3.5

144

10.6

159

4.4

170

4.5

196

2.6

170

12.8

208

1.5

177

11.5

3333     

111

8.5

111

1.8

162

2.2

137

11

174

7.9

174

0.9

191

2.8

166

18.6

6666     

 

 

 

 

108

12.5

 

 

177

7.3

82

8.7

146s

10.1

 

 

10000     

17s

1.7

 

 

 

 

130s

15.8

 

 

 

 

 

 

119s

7.5

Positive Control

911

28.7

542

20.9

463

27.3

369

45.8

478

22.5

305

23.5

410

10

388

19.2

 

Strain TA 98

Dose

No Activation

No Activation

10% HLI

30% HLI

10% RLI

30% RLI

 

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

 

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

 

0     

16

4.1

19

1.2

24

2.9

27

1.8

29

1.5

28

3.2

33     

 

 

19

2.4

 

 

 

 

 

 

 

 

100     

22

0.7

15

2.2

24

1.9

25

4.5

28

0.7

27

0.6

333     

17

0.3

20

1.8

26

2.6

24

0.3

25

1.2

29

2.3

1000     

21

0

14

2.7

20

0.7

30

3.2

26

1.5

27

0.6

3333     

14

2.1

14

1

24

2.1

25

3.2

26

0.9

28

2.3

6666     

3t

2.5

 

 

17

0.9

21

5

21

2.6

16s

1.2

Positive Control

538

10.7

543

12.7

1359

38.1

373

19.3

250

25.3

160

2.7

 

Strain TA 1537

Dose

No Activation

30% HLI

30% RLI

 

(Negative)

(Negative)

(Negative)

 

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

 

0     

8

2.4

13

0.6

12

3.4

100     

8

1.2

12

1.9

10

1.7

333     

9

1.2

9

2.1

9

1.3

1000     

7

1.5

9

1.8

7

1

3333     

6

1.5

9

2.3

6

0.9

10000     

2s

0.9

4

0.7

3

1.5

Positive Control

425

29.5

40

1.7

39

0.6

 

Abbreviations:

RLI = induced male Sprague Dawley rat liver S9

HLI = induced male Syrian hamster liver S9

s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

 

Conclusions:
Interpretation of results:negative

Amyl alcohol did not produce a mutagenic response in any of the Salmonella tester strains, in the presence or absence of metabolic activation.
Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, pentan-1-ol/Amyl alcohol need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Executive summary:

Amyl alcohol did not produce a mutagenic response in any of the Salmonella tester strains, in the presence or absence of metabolic activation.

Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore,pentan-1-ol/Amyl alcoholneed to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.

Endpoint:
in vitro DNA damage and/or repair study
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, pentan-1-ol/Amyl alcohol need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Qualifier:
equivalent or similar to
Guideline:
EU Method B.18 (DNA Damage and Repair - Unscheduled DNA Synthesis - Mammalian Cells In Vitro)
Principles of method if other than guideline:
The study was conducted according to the method described by Miller BM et al. (1995). Environ. Mol. Mutagen 26: 240-247.
GLP compliance:
not specified
Type of assay:
in vitro mammalian cell micronucleus test
Target gene:
not applicable
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
Details on mammalian cell lines (if applicable)
- Type and identity of media: in 75 cm2 tissue culture flasks at 37°C in a humidified atmosphere with 5% C02 in MEM Eagle medium supplemented with 10% heat-inactivated fetal calf serum (FCS), 2 mM L-glutamine, 100 IU/ml penicillin and streptomycin.
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Arcolor 1254-induced rat liver S9-mix
Test concentrations with justification for top dose:
23, 46 mM
Vehicle / solvent:
Vehicle(s)/solvent(s) used: DMSO (1% maximal concentration)
- Justification for choice of solvent/vehicle: was shown to produce no genetic toxicity effect
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: NOT_SPECIFIED
Remarks:
without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 1831 0.1 mM
Remarks:
with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: Cells were cultivated on microscope slides in quadriperm-dishes. A total of 1E+05 cells were seeded in each chamber and cultivated 24 hours before treatment. The medium was then substituted by 6 ml of fresh medium containing the test compound, and the cells were incubated for 4 hours. For experiments with metabolic activation, the test medium additionally contained 3% of S9-mix.
- Expression time (cells in growth medium): After treatment the cultures were washed twice with medium and incubated further for 24 hours.

NUMBER OF CELLS EVALUATED: Micronuclei (MN) were analyzed in 1000 cells/culture. To show reproducibility of the results 2 to 4 independent experiments were performed, and the mean MN frequency per 100 cells ± SD, was calculated.

DETERMINATION OF CYTOTOXICITY
no data
Evaluation criteria:
The test compound was classified as a clastogen when it was able to enhance the spontaneous MN frequency at least 3-fold or higher over that of the control for at least one dose tested.
Statistics:
Differences between the non-exposed control and the test substance exposed to V79 cells were tested for significance (P < 0.05) using the Student's t-test.
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
A concentration-dependent significant increase of micronuclei was found after MMS exposure (t-test; P< 0.001). A level of 0.5% spontaneous MN was found in the non-exposed control sample. After cyclophosphamide treatment used as a positive control for S9-mix metabolic activation, MN frequency was increased from 0.3 to 4.8% (single experiment). However, after exposure to the test substance the MN frequency was not significantly increased.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Mean MN frequencies ± SD calculated from 2 to 4 experiments are shown in the table:

 

Test substance

Concentration (mM)

Micronucleus frequency (%)a

Without S-9-mix

With S-9-mix

Control non-exposed

 

0.5 ± 0.3

 

Cyclophosphamide

0.1

0.3

4.8

MMS

0.25

3.4 ± 1.1

 

0.5

11.8 ± 4.4

 

1-Pentanol

23

0.8 ± 0.0

 

46

1.0 ± 0.6

 

DMSO

350

0.21 ± 0.2

1.6 ± 1.9

 

700

0.9 ± 0.2

1.1 ± 1.0

a Mean values from 2 to 4 experiments ± SD

 

Conclusions:
Interpretation of results :negative

No mutagenic activity of Amyl Alcohol detected.Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, pentan-1-ol/Amyl alcohol need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Executive summary:

No mutagenic activity of Amyl Alcohol detected. Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore,pentan-1-ol/Amyl alcoholneed to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction:QSAR method for chemicals properties assessment. Relevant for in vitro (Ames test) mutagenicity endpoints.
Qualifier:
according to
Guideline:
other: ToxTree: Benigni/Bossa rules for carcinogenicity and mutagenicity
Principles of method if other than guideline:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.
GLP compliance:
no
Remarks:
not applicable. QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.
Type of assay:
other: QSAR model
Target gene:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs).
Species / strain / cell type:
S. typhimurium TA 100
Test concentrations with justification for top dose:
QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.
Untreated negative controls:
other: QSAR model
Negative solvent / vehicle controls:
other: QSAR model
True negative controls:
other: QSAR model
Positive controls:
other: QSAR model
Details on test system and experimental conditions:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree.
Evaluation criteria:
This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
other: QSAR model
Untreated negative controls validity:
other: QSAR model
Additional information on results:
Benigni/Bossa rules for carcinogenicity and mutagenicity:
- Structural Alert for genotoxic carcinogenicity NO
- Potential S. typhiunium TA100 mutagen based on QSAR NO
- Negative for genotoxic carcinogenicity YES

1.6. Profiling results:

DNA binding by OECD

No alert found

Est rogen Receptor Binding

Non binder, non cyclic structure

OECD HPV Chemical Categories

Not categorized

Protein binding by OECD

No alert found

Protein binding potency

Not possible to classify according to these rules (GSH)

Superfragments

No superfragment

Toxic hazard classification by Cramer (original)

High (Class III)

US-EPA New Chemical Categories

Not categorized

Conclusions:
Interpretation of results ):negative
No alert found.The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS.
The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and therefore S-allyl O-pentyl dithiocarbonate does not cause in vitro mutagenicity (Ames test)
Executive summary:

The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and does not cause in vitro mutagenicity (Ames test).

No mutagenic activity in the (Q)SAR study, In vitro mutagenicity (Ames test) alerts by ISS for  S-allyl O-pentyl dithiocarbonate

and does not cause in vitro mutagenicity (Ames test) .This QSAR method is Relevant for in vitro (Ames test) mutagenicity endpoints.

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

Genetic toxicity in vivo

Description of key information

There are conclusive but not suffcient data for the classification of substance S-allyl O-pentyl dithiocarbonate with regard to mutagenicity/genetic toxicity. It is concluded that the substance S-allyl O-pentyl dithiocarbonate does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Qualifier:
according to
Guideline:
OECD Guideline 483 (Mammalian Spermatogonial Chromosome Aberration Test)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.23 (Mammalian Spermatogonial Chromosome Aberration Test)
Qualifier:
according to
Guideline:
EPA OPP 84-2
GLP compliance:
yes
Type of assay:
mammalian germ cell cytogenetic assay
Species:
mouse
Strain:
NMRI
Sex:
male
Details on test animals and environmental conditions:
- Source: Charles River, Germany
- Age at study initiation: min. 10 weeks
- Weight at study initiation: ca. 30 g
Route of administration:
oral: gavage
Vehicle:
0.5% carboxymethylcellulose
Duration of treatment / exposure:
6, 24 and 48 h
Frequency of treatment:
Single application
Post exposure period:
n.a.
Remarks:
Doses / Concentrations:
20, 67 and 200 mg/kg b.w.
Basis:
nominal conc.
No. of animals per sex per dose:
5 males (positive control only 4)
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (CPA)
- Dose: 140 mg/kg b.w.
Tissues and cell types examined:
Spermatogonia
Details of tissue and slide preparation:
In the test article and the negative control groups 100 well spread metaphases per animal were scored for cytogenetic damage on coded slides. In the positive control group 50 metaphases per animal were scored. Only metaphases with the characteristic chromosome number of 40 were included in the analysis. To describe a cytotoxic effect the mitotic index (% cells in mitosis) was determined.
Five animals per test group were evaluated as described. The remaining animals of each test group were evaluated in case animals died in its test group.
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
Tested in pre-experiments.
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Group

Dose [mg/kg]

Exposure [h]

No. of cells scored

Aberrant cells [%]

Mitotic index [%]

Incl. gaps

Excl. gaps

Ziram

200

6

500

0.0

0.0

1.40

Vehicle control

0

24

500

0.4

0.2

2.80

Ziram

20

24

500

0.0

0.0

1.40

Ziram

67

24

500

0.2

0.0

2.34

Ziram

200

24

500

0.2

0.2

1.84

Positive control

140

24

200

8.0

7.5

0.34

Ziram

200

48

500

0.8

0.4

1.16

Conclusions:
Interpretation of results : negative
No mutagenic activity of Ziram detected.Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Qualifier:
according to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.11 (Mutagenicity - In Vivo Mammalian Bone-Marrow Chromosome Aberration Test)
GLP compliance:
yes
Type of assay:
chromosome aberration assay
Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
- Source: BRL Tierfarm Füllinsdorf, Switzerland
- Age at study initiation: min. 10 weeks
- Weight at study initiation: ca. 30 g
Route of administration:
oral: gavage
Vehicle:
Carboxymethylcellulose
Duration of treatment / exposure:
6, 24 and 48 h
Frequency of treatment:
Single application
Post exposure period:
n.a.
Remarks:
Doses / Concentrations:
0, 40, 120 and 400 mg/kg b.w.
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (CPA)
- Dose: 20 mg/kg b.w.
Tissues and cell types examined:
Bone marrow cells
Details of tissue and slide preparation:
At least 50 well spread metaphases per animal were scored for cytogenetic damage on coded slides. Only metaphases with the characteristic chromosome number of 40 were included in the analysis. To describe a cytotoxic effect the mitotic index (% cells in mitosis; 1000 cells are scored) was determined.
Five animals per sex and group were evaluated as described. The remaining animal of each test group was evaluated in case an animal died in its test group spontaneously or due to gavage error.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
Tested in pre-experiments.
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Group

Dose [mg/kg]

Exposure [h]

No. of cells scored

Aberrant cells [%]

Mitotic index [%]

Incl. gaps

Excl. gaps

Ziram

400

6

500

0.4

0.2

3.54

Vehicle control

0

24

500

0.4

0.0

4.91

Ziram

40

24

500

1.0

0.6

4.03

Ziram

120

24

500

0.6

0.0

5.50

Ziram

400

24

500

1.6

1.2

3.52

Positive control

20

24

500

28.4

27.8

5.00

Ziram

400

48

500

0.2

0.2

5.08

Conclusions:
Interpretation of results : negative
No mutagenic activity of Ziram detected. Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
No positive control.
Qualifier:
according to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Qualifier:
according to
Guideline:
EPA OPP 84-2
GLP compliance:
yes
Type of assay:
micronucleus assay
Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River, USA
- Age at study initiation: 5-6 weeks
- Weight at study initiation: no data
Route of administration:
oral: feed
Duration of treatment / exposure:
89 days
Frequency of treatment:
daily
Post exposure period:
none
Remarks:
Doses / Concentrations:
0, 25, 75, 225 and 675 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes, plain diet
Tissues and cell types examined:
Peripheral blood
Details of tissue and slide preparation:
Peripheral blood smears were prepared from 5 male and 5 female animals in each group. The smears were stained using Giemsa then examined by light microscopy for the presence of micronuclei in normochromatic and polychromatic erythrocytes (1000 cells of each type were examined from each animal). The ratio of polychromatic to normochromatic erythrocytes was assessed by examination of at least 1000 erythrocytes from each animal.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined

Dose level [ppm]

Ration p/n (mean)

Incidence mnp (mean)

Incidence mnn (mean)

Control

0.108

0.9

1.1

25*

0.143

0.6

1.7

75**

0.124

1.2

2.0

225

0.095

0.8

0.7

675

0.135

0.5

1.2

p/n Ratio of polychromatic to normochromatic erythrocytes

mnp No. of micronucleated cells observed per 1000 polychromatic erythrocytes

mnn No. of micronucleated cells observed per 1000 normochromatic erythrocytes

* Prepared at 29 ppm initially to allow for loss during storage

** Prepared at 83 ppm initially to allow for loss during storage

 

Conclusions:
Interpretation of results : negative
No mutagenic activity of Ziram detected.Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
not specified
Type of assay:
micronucleus assay
Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (UK)
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 16.1-26 g
- Assigned to test groups randomly: yes
- Housing: high density polypropylene cages with stainless steel taps
- Diet: ad libitum
- Water: supplied via a polythene bottle and sipper tube
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 55 ±15 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12
Route of administration:
inhalation: vapour
Vehicle:
no vehicle used
Details on exposure:
TYPE OF INHALATION EXPOSURE: snout only

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
-Animals were exposed to the test material by snout-only inhalation. Prior to exposure of animals, the test material atmospheres were generated for each exposure chamber and samples analysed. Each mouse was placed in an individual polymethyl methacrylate restraining tube so that only the snout protruded. Each restraining tube was marked with the animal and group numbers. The restraining tubes were attached to the appropriate chamber so that the snout of each mouse projected into the lumen of the chamber. When the pre-exposure observations were complete, the syringe pump was switched on and the exposure timed for six hours following a 4.5 minute equilibration period, the theoretical time required for the concentration of vapour to reach 90% of its final value under the conditions of exposure employed (Silver and Arsenal, 1946). After six hours, the test atmosphere
supply was switched off and the mice removed from the restraining tubes for examination.
Duration of treatment / exposure:
6 h
Frequency of treatment:
once
Remarks:
Doses / Concentrations:
0, 467, 1558, 4675 mg/m3 (150, 500, 1500 ppm)
Basis:
nominal conc.
No. of animals per sex per dose:
10 (5 for positive control)
Control animals:
yes
Positive control(s):
chlorambucil
- Route of administration: oral
- Doses / concentrations: 30 mg/kg
Tissues and cell types examined:
bone marrow erythrocytes
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: based on the preliminary toxicity testing

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): samples were taken 24 and 48 h after treatment

DETAILS OF SLIDE PREPARATION: Animals were killed by cervical dislocation following carbon dioxide inhalation. Femurs from each animal were rapidly dissected out and cleaned of adherent tissue. The epiphyses were cut off to obtain access to the marrow canal. Marrow cells were flushed out with 2.5 ml foetal calf serum using a syringe and needle. The recovered cells were centrifuged at 1000 rpm for five minutes. The bulk of the supernatant fluid was discarded and the cell pellet resuspended in the remaining fluid. Single drops of the cell suspension were transferred to clean, dry slides, two or three smears (for the preliminary toxicity test or main micronucleus test respectively) prepared, and the slides left to air-dry. Following fixation in methanol for ten minutes, they were stained manually in 5% Giemsa stain (in Sorensen's buffer: pH 6.8), washed in buffer, air-dried, cleared for five minutes in xylene and made permanent using DPX mountant.


METHOD OF ANALYSIS: The slides were examined under the light microscope. At high magnification (x 1000, oil immersion) a total of at least 2000 erythrocytes per animal were examined. Each erythrocyte scored was classed as polychromatic or mature. Each erythrocyte scored was also examined for the presence or absence of micronuclei. Thereafter, the frequencies of micronucleated cells per 1000 erythrocytes were calculated. The ratio of polychromatic to mature cells was also determined (indicating the rythm of cell division). The frequency of micronuclei in polychromatic cells provides an index of induced genetic damage.
Evaluation criteria:
Positive for clastogenicity was a statistically and biologically significant increase in micronucleated polychromatic cells, compared to vehicle control, in at least one treatment group; particularly if supported by evidence of a dose-related response.
Statistics:
Mann-Whitney U procedure (Mann and Whitney, 1942), two-tailed test, one-tailed test.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: 45, 150, 450, 1500, 2000 ppm
- Clinical signs of toxicity in test animals: unconscious and death at 2000 ppm, unconscious, slow and laboured respiration, all extremities red coloured. No adverse reactions to treatment were observed in animals exposed to 450, 150, 45 ppm test substance.
- Evidence of cytotoxicity in tissue analyzed: no bone marrow toxicity observed
- Harvest times: 48 hours

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): see table
- Ratio of PCE/NCE (for Micronucleus assay): see table

The micronucleus test - group means and standard deviations (sd) by sex

test group

dose (ppm)

sampling time (h)

Sex

total polychromatic cells scored

total micronucleated polychromatic cells

mean micronucleated polychromatic cells per 1000 and sd

total mature cells scored

total micronucleated mature cells per 1000 and sd

polychromatic cells/mature cells

Air

0

24

M

5183

7

1.3±0.9

5652

4

0.7±0.4

F

5709

3

0.5±0.5

5607

3

0.6±0.9

Carbon disulphide

150

M

5208

2

0.4±0.5

5871

4

0.6±0.9

F

6030

6

1.0±0.7

5469

5

0.9±0.8

500

M

6194

14

2.0±1.6

5505

2

0.4±0.5

F

5788

10

1.6±1.1

5148

3

0.6±0.5

1500

M

6713

8

1.0±1.2

5089

2

0.4±0.5

F

7640

9

1.2±0.9

5129

2

0.4±0.5

Chlorambucil

30 mg/kg

M

5473

322

59.0±27.6

5176

3

0.6±0.9

F

5807

403

69.3±27.5

5201

7

1.3±0.8

Air

0

48

M

5090

4

0.8±0.8

6101

7

1.1±0.8

F

5588

4

0.7±0.8

4561

1

0.2±0.4

Carbon disulphide

150

M

5353

2

0.4±0.5

5699

4

0.7±0.6

F

5976

9

1.5±1.1

5079

0

0.0±0.0

500

M

6153

7

1.1±1.2

5300

3

0.6±0.9

F

6518

6

0.9±0.6

5105

2

0.4±0.5

1500

M

7324

8

1.0±0.9

5072

0

0.0±0.0

F

6558

15

2.1±1.4

5022

0

0.0±0.0

 

Conclusions:
Interpretation of results : negative
No evidence of induced chromosomal or other damage leading to the formation of micronuclei in erythrocytes of the bone marrow was detected after exposure of the animals to CS2 via inhalation.
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Executive summary:

The effect of carbon disulphide on chromosome structure in the bone marrow erythrocytes of mice was examined. The animals (males and females) were exposed via inhalation snout-only, for 6 h to the following concentrations: 0, 467, 1558, 4675 mg/m3 (0, 150, 500, 1500 ppm). The exposure concentrations were based on a preliminary toxicity test. Chlorambucil (30 mg/kg bw) was used as a positive control, adminstered via the oral route. Animals were sacrifised and examined 24 and 48 h after exposure. No evidence of induced chromosomal or other damage leading to the formation of micronuclei in erythrocytes of the bone marrow was detected, uder the present test condition, after exposure of the animals to CS2 via inhalation. Mice exposed at 1500 ppm, however, showed a small increase in the ratio of polychromatic/mature cells, which may indicate disturbance of erythropoiesis. Carbon disulphide was tested for induction of micronuclei in the bone marrow ertythrocytes of mice according to the OECD Guidelines 474 (1983).

Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: other: review paper covering many studies
Type of information:
other: published data
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Qualifier:
no guideline available
Principles of method if other than guideline:
Review of a large series of publications on studies in which a wide array of methods was applied.
GLP compliance:
not specified
Type of assay:
other: review paper covering many studies
Species:
other: A series of studies with various animal species was reviewed.
Strain:
other: A series of studies with various animal species was reviewed.
Sex:
male/female
Details on test animals and environmental conditions:
Not applicable: review paper.
Route of administration:
other: Invasive (injection) and non-invasive (inhalation, oral, dermal) routes were employed in the different studies reviewed.
Vehicle:
Not applicable: review paper.
Details on exposure:
Not applicable: review paper.
Duration of treatment / exposure:
Not applicable: review paper.
Frequency of treatment:
Not applicable: review paper.
Conclusions:
Interpretation of results : negative
In the majority of the in vivo tests assessing CS2 mutagenic potential, a negative result was obtained, except for one case. The validity of the studies is uncertain due to technical issues (e.g. invalid controls).
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
Executive summary:

In male and female rats inhaling 63 or 125 mg carbon disulfide/m3, 7 hours per day for 1 or 5 days, there was no significant increase in the frequency of chromosomal aberrations in bone marrow cells (Belisles et al., 1980). In another study (Vasil’eva, 1982), oral exposure to carbon disulfide gave a mutagenic response, manifested as chromosomal aberrations and polyploid cells in the bone marrow of female rats and in rat embryos exposed on days 10–13 of gestation. According to the reviewer,'it is difficult to assess the validity of these findings, as the reporting was brief e.g., the statistical significance was often not indicated and the effective dose was not reported, except to indicate that it was one-tenth of the LD50 '. In the investigation of Belisles et al. (1980), male rats were exposed to 63–125 mg/m3 of CS2, 7 h/d for 5 d; no significant increase in dominant lethal mutations was observed, nor was there a dose related increase in sperm abnormalities in rats or mice exposed according to the same protocol. However, lack of an effect on sperm abnormalities in positive control rats suggests that there was a problem with the test methods in this study.

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

Additional information

Additional information from genetic toxicity in vitro:  

 

No mutagenic activity of CS2 detected in the reliable study of Akzo Chemicals International BV 1992.Carbon disulphide was examined for its mutagenic activity in four histidine-dependent auxotrophs of Salmonella typhimurium, strains TA98, TA100, TA1535, TA1537.

Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.

 

No mutagenic activity of Pentan-1-ol/Amyl alcohol detected in the reliable study. Amyl alcohol did not produce a mutagenic response in any of the Salmonella tester strains, in the presence or absence of metabolic activation.

Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore,pentan-1-ol/Amyl alcoholneed to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.

 

No mutagenic activity of Pentan-1-ol/Amyl alcohol detected in vitro DNA damage and/or repair study

Pentan-1-ol/Amyl alcohol is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore,pentan-1-ol/Amyl alcoholneed to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.

 

No mutagenic activity of Ziram detectedin the reliable study of Brooker, P.C. & Akhurst, L.C.1989.

Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2

 

No mutagenic activity in the (Q)SAR study, In vitro mutagenicity (Ames test) alerts by ISS for S-allyl O-pentyl dithiocarbonate

and does not cause in vitro mutagenicity (Ames test) .This QSAR method is Relevant for in vitro (Ames test) mutagenicity endpoints.

 

 Justification for selection of genetic toxicity endpoint Negative in all test conducted.

Justification for classification or non-classification

Based on the hazard assessment of S-allyl O-pentyl dithiocarbonate in section 2.1 and 2.2. in IUCLID 6, available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

 

Directive 67/548

Mutagenicity-Genetic Toxicity

Muta. Cat. 1; R46 May cause heritable genetic damage.

Muta. Cat. 2; R46 May cause heritable genetic damage.

Muta. Cat. 3; R68 Possible risk of irreversible effects.

CLP

Germ cell mutagenicity

Muta. 1A

Muta. 1B

Muta. 2

H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

 

It is concluded that the substance S-allyl O-pentyl dithiocarbonate does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity