S-allyl O-pentyl dithiocarbonate

Endpoint summary

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

Reference

Reference 1

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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only 4 bacterial strains tested

Qualifier:

according to guideline

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).

Reference 2

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

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

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

Reference 3

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

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.

Reference 4

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

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.

Reference 5

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

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

Reference

Reference 1

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

Guideline:

OECD Guideline 483 (Mammalian Spermatogonial Chromosome Aberration Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.23 (Mammalian Spermatogonial Chromosome Aberration Test)

Qualifier:

according to guideline

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 or test system 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

Reference 2

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

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

no

Qualifier:

according to guideline

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 or test system 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

Reference 3

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

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

No positive control.

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Qualifier:

according to guideline

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 or test system 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

Reference 4

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

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 or test system 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).

Reference 5

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 or test system 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