O-isobutyl ethylthiocarbamate

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 O-isobutyl ethylthiocarbamate (IBETC) with regard to mutagenicity/genetic toxicity. It is concluded that the substance O-isobutyl ethylthiocarbamate (IBETC) 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:

(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

Profiling results:

1.1. CAS number:55860-53-2

1.2. Other regulatory numbers: Not reported

1.3. Chemical name(s):

carbamothioic acid, ethyl-, o-(2-methylpropyl) ester

o-isobutyl ethylthiocarbamate

o-(2-methylpropyl) ethylcarbamothioate

1.4. Structure codes:

a. SMILES:

CCNC(=S)OCC(C)C

1.5. 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

-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 O-isobutyl ethylthiocarbamate (IBETC) 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  O-isobutyl ethylthiocarbamate (IBETC)

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

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:

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

Clastogenic effects were studied by the micronucleus test using the Chinese hamster V79 cell line as a target.

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell micronucleus test

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: MEM Eagle medium (V79 cells) supplemented with 10% heat-inactivated fetal calf serum (FCS), 2 mM L-glutamine, 100 IU/ml penicillin and streptomycin.- Properly maintained: yes- Periodically checked for Mycoplasma contamination: no data- Periodically checked for karyotype stability: no data- Periodically "cleansed" against high spontaneous background: no data

Metabolic activation:

without

Test concentrations with justification for top dose:

11 and 53 mM

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [no data]

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in mediumDURATION- Exposure duration: 4 hours at 37 °C- Expression time (cells in growth medium): additional 24 hoursNUMBER OF CELLS EVALUATED: 1000 cells/cultureDETERMINATION OF CYTOTOXICITY - Method: relative total growth

Evaluation criteria:

The test compound was classified as a clastogen when it was able to enhance the spontaneous MN frequency at least three-fold or higher over that of the control for at least one dose tested.

Statistics:

no data

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No mutagenic activity of Isobutyl Alcohol detected. Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results :negative No mutagenic activity of Isobutyl Alcohol detected.
Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

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:

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The mutagenicity of the test chemical was examined in Salmonella typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) and Escherichia coli (WP2uvrA) using the preincubation method with and without S9 mix.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA1538

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

5; 10; 50; 100; 500; 1000; 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [water]- Justification for choice of solvent/vehicle: none given

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: TA98, TA100 and E.coli WP2 uvrA:2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide; TA1535: N-ethyl-N-nitro-N-nitrosoguanidine; TA1537: 9-aminoacridine; TA1538: 4-nitroquinoline-N-oxide

Remarks:

without S-9 mix

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: TA100, TA98, TA1537 and TA1538: benzo(a)pyrene; TA1535 and E.coli WP2 uvrA: 2-aminoanthracene

Remarks:

with S-9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubationDURATION- Preincubation period: 20 min at 37 °c- Exposure duration: 2 days at 37 °CDETERMINATION OF CYTOTOXICITY - Method: relative total growth

Evaluation criteria:

no data

Statistics:

no data

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No mutagenic activity of Isobutyl Alcohol detected.Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results :negative with metabolic activationnegative without metabolic activationNo mutagenic activity of Isobutyl Alcohol detected.
Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Reference 4

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:

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The test substance was tested for mutagenicity in Salmonella typhimurium, using a preincubation protocol. The test was performed in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA97 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

100 - 10000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [DMSO]- Justification for choice of solvent/vehicle: none given

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Without S9: sodium azide (TA1535 and TA100), 9-aminoacridine (TA97 and TA1537), 4-nitro-o-phenylenediamine (TA98). With S9: 2-aminoanthracene (all strains)

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubationDURATION- Preincubation period: 20 min at 37 °C- Exposure duration: 2 days at 37 °CDETERMINATION OF CYTOTOXICITY - Method: relative total growth

Evaluation criteria:

Evaluations were made at both the individual trial and overall chemical levels. Individual trials were judged mutagenic: (+), weakly mutagenic (+W), questionable (?), or nonmutagenic (-), depending on the magnitude of the increase of his+ revertants, and the shape of the dose-response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of "+ W", if only a single dose was elevated over the control, or if the increase seen was not dose related. The distinctions between a questionable mutagenic response and a nonmutagenic or weak mutagenic response and between a weak mutagenic response and mutagenic response are highly subjective. It was not necessary for a response to reach twofold over background for a chemical to be judged mutagenic.A chemical was judged mutagenic (+) or weakly mutagenic (+W) if it produced a reproducible dose-related response over the solvent control in replicate trials. A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a "+W" response, or if only single doses produced increases in his' revertants in repeat trials.Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response. The chemicals were decoded by the chemical repository only after a determination had been made regarding their mutagenicity or nonmutagenicity.

Statistics:

no data

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA97, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

reduction of the background lawn at the highest concentration tested in some strains without S-9 mix

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY:Reduction of the background lawn at the highest concentration tested in TA100, TA1535, TA97 and TA98 without S-9 mix
Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results:negative with metabolic activationnegative without metabolic activationNo mutagenic activity of Isobutyl Alcohol detected.
Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Reference 5

Endpoint:

in vitro gene mutation study in mammalian cells

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:

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Principles of method if other than guideline:

The test substance was evaluated for mutagenic effects by the hypoxanthine-guanine-phosphoribosyl transferase gene mutation test (HPRT test).

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Target gene:

hypoxanthine-guanine-phosphoribosyl transferase gene

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: MEM Eagle medium (V79 cells) supplemented with 10% heat-inactivated fetal calf serum (FCS), 2 mM L-glutamine, 100 IU/ml penicillin and streptomycin.- Properly maintained: yes- Periodically checked for Mycoplasma contamination: no data- Periodically checked for karyotype stability: no data- Periodically "cleansed" against high spontaneous background: no data

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

up to 107 mM

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [no data]

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in mediumDURATION- Exposure duration: 2 hours- Expression time (cells in growth medium): 7 days- Selection time (if incubation with a selection agent): 7 days- Fixation time (start of exposure up to fixation or harvest of cells): ca. 14 daysSELECTION AGENT (mutation assays): 6-thioguanineDETERMINATION OF CYTOTOXICITY - Method: cloning efficiency

Evaluation criteria:

The test compound was classified as a mutagen when it was able to enhance in a concentration-depended manner the spontaneous HPRT frequency by a factor of three or more.

Statistics:

no data

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

no cytotoxicity observed up to 107 mM

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No mutagenic activity of Isobutyl Alcohol detected.Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results :negative
No mutagenic activity of Isobutyl Alcohol detected.Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Reference 6

Endpoint:

in vitro gene mutation study in mammalian cells

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:

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Principles of method if other than guideline:

The test substance was evaluated for mutagenic effects in the L5178Y thymidine kinase mouse lymphoma cell assay.

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Target gene:

thymidine kinase gene

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

- Type and identity of media: The cells were maintained in Fischer's medium for leukemic cells of mice with 10% horse serum and sodium pyruvate. Cloning medium consisted of Fischer's medium with 10 % horse serum, sodium pyruvate, and 0 .35% Noble agar. Selection medium was made from cloning medium by the addtion of 5 ml BrdU to 100 ml cloning medium.- Properly maintained: yes- Periodically checked for Mycoplasma contamination: no data- Periodically checked for karyotype stability: no data- Periodically "cleansed" against high spontaneous background: yes

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

up to 12.5 µl/ml without activation (10 mg/ml); up to 6.25 µg/ml (5 mg/ml) with activation

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [water]- Justification for choice of solvent/vehicle: Isobutyl Alcohol, was partially soluble in sterile, deionized water at a concentration of 250 µl/ml and was then further diluted for testing.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

without S-9 mix

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

no

Positive control substance:

other: Dimethylnitrosamine

Remarks:

with S-9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: in mediumDURATION- Exposure duration: 4 hours at 37 °C- Expression time (cells in growth medium): 2-3 days- Selection time (if incubation with a selection agent): 10 days- Fixation time (start of exposure up to fixation or harvest of cells): ca. 12-13 daysSELECTION AGENT (mutation assays): bromodeoxyuridine (BrdU)DETERMINATION OF CYTOTOXICITY - Method: relative total growth

Evaluation criteria:

A compound is considered mutagenic in this assay if:- A dose-response relationship is observed over 3 of the 5 dose levels employed.- The minimum increase at the low level of the dose-response curve is at least 2.5 times greater than the solvent and/or negative control values.- The solvent and negative control data are within the normal range of the spontaneous background for the TK locus.Occasionally, a single point within a concentration range will show an increase 2.5 times greater than the spontaneous background. If the increase is at the high dose, is reproducible, and if an additional higher dose level is not feasible because of toxicity, the chemical can be considered mutagenic, if the increase is internal within the dose range and is not reproducible, the increase will normally be considered aberrant. If the internal increase is reproducible, several doses clustered around the positive concentration will be examined to either confirm or reject the reliability of the effect.

Statistics:

no data

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

highly cytotoxic (survival at 3%) at 12.5 µl/ml without S-9 mix

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY:The test substance was highly cytotoxic at 12.5 µl/ml when tested without S-9 mix. At all other concentration tested with and without S-9 mix, the relative growth was > 30%.Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results :negativeNo mutagenic activity of Isobutyl Alcohol detected.
Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Reference 7

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 Thionocarbamate.

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:

not specified

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 Thionocarbamate.

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 O-isobutyl ethylthiocarbamate (IBETC) with regard to mutagenicity/genetic toxicity. It is concluded that the substance O-isobutyl ethylthiocarbamate (IBETC) 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 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:

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

not specified

Type of assay:

micronucleus assay

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Charles River Germany- Age at study initiation: 5-8 weeks- Weight at study initiation: mean: 26 g- Assigned to test groups randomly: [yes, under following basis: Male and female animals were assigned to the test groups according to a randomization plan prepared with an appropriate computer program.]- Housing: in groups of 5 during the acclimation period, individually later on- Diet: ad libitum - Water: ad libitum- Acclimation period: 3-5 days ENVIRONMENTAL CONDITIONS- Temperature (°C): 20-24 °C- Humidity (%): 30-70 %- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: [olive oil]- Justification for choice of solvent/vehicle: Due to the insolubility of the test substance in water, olive oil was selected as the vehicle, which had been demonstrated to be suitable in the in vivo micronucleus test and for which historical data are available.- Concentration of test material in vehicle: 5 g/100 ml; 10 g/100 ml and 20 g/100 ml- Amount of vehicle (if gavage or dermal): 10 ml/kg

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:The substance to be administered per kg body weight was dissolved in olive oil and prepared immediately before administration.- The 500 mg/kg group was given 500 mg test substance/kg body weight or 10 ml/kg body weight of a solution with a concentration of 5 g/100 ml.- The 1000 mg/kg group was given 1000 mg test substance/kg body weight or 10 ml/kg body weight of a solution with a concentration of 10 g/100 ml.- The 2000 mg/kg groups were given 2000 mg test substance/kg body weight or 10 ml/kg body weight of a solution with a concentration of 20 g/100 ml.

Duration of treatment / exposure:

single application

Frequency of treatment:

single application

Post exposure period:

24 and 48 hours

Remarks:

Doses / Concentrations:500, 1000, 2000 mg/kg bwBasis:nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide (CPP); vincristine sulphate (VCR)- Justification for choice of positive control(s): Both positive control articles (CPP and VPR) are well-defined clastogens and aneugens respectively.- Route of administration: orally or intraperitoneally- Doses / concentrations: 20 mg/kg bw (CPP) / 0.15 mg/kg bw (VCR)

Tissues and cell types examined:

In general, 2000 polychromatic erythrocytes (PCE) from each of the male and female animals of every test group are evaluated and investigated for micronuclei (MN) . The normochromatic erythrocytes (NCE) which occur are also scored. The cells were prepared from the bone marrow of two femora from animals either sacrificed 24 or 48 hours after dosing.

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: In a pretest for the determination of the acute oral toxicity, all animals (male and female) survived treatment with 2000 mg/kg body weight recommended as the highest dose according to the OECD Guideline. As clinical signs only piloerection was observed.Therefore, a dose of 2000 mg/kg body weight was selected as the highest dose in the present cytogenetic study. 1000 mg/kg and 500 mg/kg body weight were administered as further doses.TREATMENT AND SAMPLING TIMES (in addition to information in specific fields):The animals were treated once and samples of bone marrow were taken 24 hours and 48 hours after the treatment.DETAILS OF SLIDE PREPARATION:The bone marrow was prepared according to the method described by SCHMID, W.- The two femora were prepared by dissection and removing all soft tissues.-After cutting off the epiphyses, the bone marrow was flushed out of the diaphysis into a centrifuge tube using a cannula filled with fetal calf serum which was at 37°C (about 2 ml/femur).-The suspension was mixed thoroughly with a pipette, centrifuged at 300 x g for 5 minutes, the supernatant was removed and the precipitate was resuspended in about 50 µl fresh FCS.- 1 drop of this suspension was dropped onto clean microscopic slides, using a Pasteur pipette. Smears were prepared using slides with ground edges, the preparations were dried in the air and subsequently stained. The slides were stained in eosin and methylene blue solution for 5 minutes (May Grünwald solution modified = Wrights solution), rinsed in purified water and then placed in fresh purified water for 2 or 3 minutes. They were finally stained in 7.5% Giemsa solution for 15 minutes. After being rinsed twice in purified water and clarified in xylene, the preparations were mounted using Corbit-BalsamMETHOD OF ANALYSIS:In general, 2000 polychromatic erythrocytes (PCE) from each of the male and female animals of every test group are evaluated and investigated for micronuclei (MN). The normochromatic erythrocytes (NCE) which occur are also scored. The following parameters are recorded:- Number of polychromatic erythrocytes- Number of polychromatic erythrocytes containing micronucleiThe increase in the number of micronuclei in polychromatic erythrocytes of treated animals as compared with the solvent control group provides an index of a chromosome-breaking (clastogenic) effect or of a spindle activity of the substance tested.- Number of normochromatic erythrocytes- Number of normochromatic erythrocytes containing micronucleiThe number of micronuclei in normochromatic erythrocytes at the early sacrifice intervals shows the situation before test substance administration and may serve as a control value. A substance-induced increase in the number of micronuclei in normocytes may be found with an increase in the duration of the sacrifice intervals. - Ratio of polychromatic to normochromatic erythrocytes An alteration of this ratio indicates that the test substance actually reached the targetIndividual animals with pathological bone marrow depression may be identified and excluded from the evaluation.- Number of small micronuclei (d < D/4) and of large micronuclei (d > D/4) (d = diameter of micronucleus, D = cell diameter)The size of micronuclei may give an indication on the possible mode of action of the test substance, i.e. a clastogenic or a spindle poison effect.Slides were coded before microscopic analysis.

Evaluation criteria:

The test chemical is to be considered positive in this assay if the following criteria are met:- A dose-related and significant increase in the number of micronucleated polychromatic erythrocytes at any of the intervals.- The proportion of cells containing micronuclei exceeded both the values of the concurrent negative control range and the negative historical control range.A test substance is generally considered negative in this test system if:- There was no significant increase in the number of micronucleated polychromatic erythrocytes at any dose above concurrent control frequencies and at any time.- The frequencies of cells containing micronuclei were within the historical control range.

Statistics:

The statistical evaluation of the data was carried out using the program system MUKERN (BASF Aktiengesellschaft).The number of micronuclei in polychromatic erythrocytes was analyzed.A comparison of the dose group with the vehicle control was carried out using the Wilcoxon test for the hypothesis of equal medians. Here, the relative frequencies of cells with micronuclei of each animal were used . If the results of this test were significant, labels (* for p < 0.05, ** for p < 0 .01) wereprinted with the group means in the tables. This test was performed one-sided.

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

narcotic like state and piloerection

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY- Dose range: 2000 mg/kg- Clinical signs of toxicity in test animals: piloerectionRESULTS OF DEFINITIVE STUDYThe single oral administration of olive oil in a volume of 10 ml/kg body weight led to 1.5 ‰ polychromatic erythrocytes containing micronuclei after the 24-hour sacrifice interval or to 1.1 ‰ after the 48-hour sacrifice interval. After the single administration of the highest dose of 2000 mg/kg body weight, 1.8 ‰ polychromatic erythrocytes containing micronuclei were found after 24 hours and 1.3‰ after 48 hours.In the two lower dose groups, rates of micronuclei of about 1.6 ‰ (1000 mg/kg group) and 1.5 ‰ (500 mg/kg group) were detected after a sacrifice interval of 24 hours in each case.With 17.9‰ the positive control substance cyclophosphamide for clastogenicity, led to the expected increase in the number of polychromatic erythrocytes containing exclusively small micronuclei at a dose level of 20 mg/kg body weight.With 67.3 ‰ the positive control vincristine for spindle poison effects also led to a clearly enhanced number of polychromatic erythrocytes containing micronuclei with the expected amount of large micronuclei, i.e. 8.0 ‰.The number of normochromatic erythrocytes containing micronuclei did not differ to any appreciable extent in the negative control or in the various dose groups at any of the sacrifice intervals.Thus, the test substance Isobutanol did not lead to any increase in the rate of micronuclei. The number of normochromatic or polychromatic erythrocytes containing small micronuclei (d < D/4) or large micronuclei (d > D/4) did not deviate from the vehicle control value at any of the sacrifice intervals and was within the historical control range.No inhibition of erythropoiesis induced by the treatment of mice with Isobutanol was detected the ratio of polychromatic to normochromatic erythrocytes was always in the same range as that of the control values in all dose groups.

Conclusions:

Interpretation of results : negative Oral gavage dose of 500, 1,000 or 2,000 mg/kg of isobutanol did not have any chromosome-damaging (clastogenic) effect, and there were noindications of any impairment of chromosome distribution in the course of mitosis.
Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Reference 2

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 Thionocarbamate.

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:

not specified

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 Thionocarbamate.

Reference 3

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 Thionocarbamate.

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:

not specified

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 Thionocarbamate.

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:

Dithiocarbamates are related compounds to Thionocarbamate.

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:

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:

- 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 ppmBasis: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 Thionocarbamate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:  

 

No mutagenic activity of the test chemical was examined in Salmonella typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) and Escherichia coli (WP2uvrA) using the preincubation method with and without S9 mix.

 

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

No mutagenic activity in the (Q)SAR study, In vitro mutagenicity (Ames test) alerts by ISS for O-isobutyl ethylthiocarbamate (IBETC)

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.

Additional information from genetic toxicity in vivo:  

Interpretation of results : negative Oral gavage dose of 500, 1,000 or 2,000 mg/kg of isobutanol did not have any chromosome-damaging (clastogenic) effect, and there were noindications of any impairment of chromosome distribution in the course of mitosis.

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Interpretation of results : negative. No mutagenic activity of Ziram  detected. Dithiocarbamates are related compounds to Thionocarbamate.

Justification for classification or non-classification

Based on the hazard assessment of O-isobutyl ethylthiocarbamate (IBETC) 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 O-isobutyl ethylthiocarbamate (IBETC) does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity