O-isopropyl 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 IPETC/O-isopropyl ethylthiocarbamate with regard to mutagenicity/genetic toxicity. It is concluded that the substance IPETC/O-isopropyl ethylthiocarbamate 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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of IPETC/ O-isopropyl ethylthiocarbamate . Therefore, Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of IPETC/O-isopropyl ethylthiocarbamate .

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

S. typhimurium strain TA102 or E. coli strain WP2 uvrA were not used & 2-aminoanthracene was the only positive control compound used to test the efficacy of the S9 fraction.

GLP compliance:

no

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 applicable

Species / strain / cell type:

S. typhimurium TA 97

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat and hamster liver microsomes (10% and 30% for strains TA 98, TA 100 and TA 1535 and 30% for strain TA 1537)

Test concentrations with justification for top dose:

100, 333, 1000, 3333, or 10000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: distilled water

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1342 5-bromo-2-deoxyuridine (-S9) and 3-methylcholanthrene (+S9)

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes at 37 ºC
- Exposure duration: 48 hours at 37 ºC

NUMBER OF REPLICATIONS: At least five doses of each chemical were tested in triplicate, and repeat experiments were performed at least one week following the initial trial.

Evaluation criteria:

Revertant colonies were counted

Statistics:

None performed (revertant colonies were counted)

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

no cytotoxicity when tested at levels ≤ 10,000 µg/plate which is higher than the limit concentration of 5,000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

no cytotoxicity when tested at levels ≤ 10,000 µg/plate which is higher than the limit concentration of 5,000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

no cytotoxicity when tested at levels ≤ 10,000 µg/plate which is higher than the limit concentration of 5,000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

other: Revertant colony count did not double in the presence of 30% hamster liver microsomes. An adequate positive control response was observed for all other tested conditions.

Species / strain:

S. typhimurium TA 97

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

no cytotoxicity when tested at levels ≤ 10,000 µg/plate which is higher than the limit concentration of 5,000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

no cytotoxicity when tested at levels ≤ 10,000 µg/plate which is higher than the limit concentration of 5,000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No mutagenic activity of Propan-2-ol (Isopropyl alcohol)

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results :
negative with metabolic activation
negative without metabolic activation

No mutagenic activity of Propan-2-ol (Isopropyl alcohol) detected. Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/ O-isopropyl ethylthiocarbamate and there is not mutagenic activity.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

key study

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 1535

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

Species / strain:

S. typhimurium TA 1537

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

Species / strain:

S. typhimurium TA 98

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

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

Species / strain:

S. typhimurium TA 102

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 categorizedcategorized

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

Reference 3

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of IPETC/ O-isopropyl ethylthiocarbamate . Therefore, Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of IPETC/O-isopropyl ethylthiocarbamate .

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

GLP compliance:

no

Type of assay:

mammalian cell gene mutation assay

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver microsomes (S9)

Test concentrations with justification for top dose:

Range-finding (cytotoxicity) assay: 0.0098, 0.0195, 0.0391, 0.0781, 0.156, 0.313, 0.625, 1.25, 2.5, or 5.0 mg/mL
Mutation assay (- & + S9): 0.5, 1.0, 2.0, 3.0, 4.0, or 5.0 mg/mL (Trial 1)
Mutation assay (- S9): 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, or 5.0 mg/mL (Trial 2)
Mutation assay (+ S9): 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5, or 5.0 mg/mL (Trial 2)
Mutation assay (- S9): 1.0, 2.0, 3.0, 4.0, 4.5, or 5.0 mg/mL (Trial 3)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: sterile, deionized water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

sterile, deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1342 5-bromo-2-deoxyuridine (-S9) and 3-methylcholanthrene (+S9)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 4 hours at 37 ºC
- Expression time (cells in growth medium): 7 days
- Selection time (if incubation with a selection agent): 7 to 10 days at 37 ºC

NUMBER OF REPLICATIONS: 3 (-S9) or 2 (+S9) independent experiments.

Evaluation criteria:

(a) A dose- or toxicity-related increase in mutant frequency must be observed for at least 3 doses.
(b) A mutagenic dose-response in one assay should be confirmed in a second mutation assay.
(c) If an increase in mutant frequency is observed in one trial for a treated culture near the highest testable toxicity and the number of mutant colonies is more than twice the value needed to indicate a significant response, the test article generally will be considered to be mutagenic.
(d) Applied concentration or toxicity (% survival) can be used to establish whether the mutagenic activity is related to an increase in effective treatment.
(e) Treatments that reduce relative clonal survival to less than 5% may be included in the assay but will not be used as sufficient evidence of mutagenicity as it relates to risk assessment.

Statistics:

Not performed (colonies are counted)

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

but tested up to limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No mutagenic activity of Propan-2-ol (Isopropyl alcohol)

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results :
negative with metabolic activation
negative without metabolic activation

No mutagenic activity of Propan-2-ol (Isopropyl alcohol) detected. Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/O-isopropyl ethylthiocarbamate and there is not mutagenic activity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of IPETC/O-isopropyl ethylthiocarbamate . Therefore, Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of IPETC/O-isopropyl ethylthiocarbamate

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

1000 polychromatic erythrocytes were evaluated per animal, rather than 2000

GLP compliance:

not specified

Type of assay:

micronucleus assay

Species:

mouse

Strain:

ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: from Harlan Sprague-Dawley, Inc., Frederick, MD
- Age at study initiation: 8 to 11 weeks old
- Assigned to test groups randomly: yes, under following basis: by a computer generated randomization program
- Housing: 5 mice/cage
- Diet (e.g. ad libitum): Purina Certified Laboratory Chow #5002 ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Quarantined for seven days before being placed on study

ENVIRONMENTAL CONDITIONS
- Temperature: Reported in the study to be 72 ± 6 ºF (approximately 22.2 ºC)
- Humidity (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12 hours: 12 hours

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: 0.9% sodium chloride

Details on exposure:

Thirty randomly assigned mice/group (15 males/15 females) were treated with isopropanol dissolved in 0.9% sodium chloride at dose levels of 0 (vehicle control), 350, 1173 and 3500 mg isopropanol/kg bw by intraperitoneal injection. Mice were observed for toxic symptoms and/or mortalities immediately after dosing and twice daily for the duration of the assay

Duration of treatment / exposure:

Single exposure

Frequency of treatment:

Single exposure

Post exposure period:

None

Remarks:

Doses / Concentrations:
350 mg/kg bw
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
1173 mg/kg bw
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
2500 mg/kg bw
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
3500 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

15/sex/dose

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Route of administration: oral (gavage)
- Doses / concentrations: 80 mg/kg bw

Tissues and cell types examined:

Bone marrow was extracted from 10 mice/group (5 males/5 females) at 24, 48, and 72 hours after dosing. An additional group of 10 mice (5 males/5 females) was treated with 3500 mg/kg bw and held to ensure that 10 mice were available for bone marrow extraction at each interval. These mice were scheduled for use only if mortalities occurred in the primary dose group. As needed, mice were randomly selected from this secondary group for bone marrow extraction and unused mice were euthanized at the completion of the trial. Bone marrow for the positive control group was harvested at 24 hours. Terminal body weights were collected on all animals prior to euthanization for bone marrow harvest.

Details of tissue and slide preparation:

At the appropriate harvest time, the animals were euthanized with CO2 and the adhering soft tissue and epiphyses of both tibias were removed. The marrow was flushed into a centrifuge tube (one tube for each animal) with 3 mL fetal calf serum. Following centrifugation to pellet the tissue, most of the supernatant was drawn off, the cells were resuspended, and the suspension spread on slides and air-dried. The slides were then fixed in methanol and stained in May-Gruenwald solution followed by Giemsa. After being air-dried, the slides were coverslipped using Depex mounting medium. The coded slides were then scored blind for micronuclei and the polychromatic (PCE) to normochromatic (NCE) cell ratio. Standard forms were used to record these data. One thousand PCEs per animal were scored. The frequency of micronucleated cells was expressed as percent micronucleated cells based on the total PCEs present in the scored optic field. The normal frequency of micronuclei in this mouse strain is about 0.0-0.4%. The frequency of PCEs versus NCEs was determined by scoring the number of NCEs observed in the optic fields while scoring the 1000 PCEs for micronuclei.

Evaluation criteria:

The criteria for the identification of micronuclei were those of Schmid (1976). Micronuclei were darkly stained and generally round, although almond and ring-shaped micronuclei occasionally occur. Micronuclei had sharp borders and were generally between 1/20 and 1/5 the size of the PCE. The unit of scoring was the micronucleated cell, not the micronucleus; thus the occasional cell with more than one micronucleus was counted as one micronucleated PCE, not two (or more) micronuclei. The staining procedure permitted the differentiation by color of PCEs and NCEs (bluish-grey and red, respectively).

Statistics:

ANOVA followed by Tukey's

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No mutagenic activity of Propan-2-ol (Isopropyl alcohol) detected.

All animals in the 3500 mg/kg bw dose group became prostrate after dosing. Within 22 hours after dosing, 35 of the 40 animals dosed at 3500 mg/kg had expired. Due to this toxicity, the 3500 mg/kg bw dose level was eliminated from the study. Immediately after dosing, the animals receiving 2500 mg/kg became prostrate. Approximately four hours after dosing, the animals were languid with squinted eyes. The following morning, approximately 23 hours after dosing, one male (#8371) was languid with squinted eyes. This animal also exhibited dyspnea approximately 30 hours after dosing. All other animals appeared normal; however, within 46 hours of dosing three animals (male #8371; female #’s 8319 and 8354) were found dead. Another female (#8369) expired approximately 53 hours after dosing and several other animals were languid. On the third morning, approximately 70 hours after dosing, two males (#’s 8326 and 8405) were found dead. All remaining test article dosed animals had rough haircoats and this condition remained at the 72 hour harvest time. A gross necropsy was performed on all animals which expired during the observation period. Male #8371 had a moderate amount of clear yellow fluid in the trachea and thoracic cavity and an irregular black stomach mucosa. Female #8369 also had a moderate amount of a clear orange fluid in the thoracic cavity. The other necropsied animals had moderate to significant distension of the stomachs or colons, two with an abnormally thin fluid content. No other abnormalities were noted in the animals examined. The terminal body weight range of the animals harvested in this trial of the micronucleus assay was 28.1 - 37.4 grams for males and 19.0 - 26.9 grams for females. Terminal body weight gains were significantly lower at the 48 and 72 hour sacrifice intervals in mice treated with 2,500 mg/kg bw compared to corresponding vehicle control body weight gains indicating that there was a test article related reduction in body weights. The test article, isopropanol, induced no significant increases in micronucleated polychromatic erythrocytes over the levels observed in the vehicle controls in either sex or at any of the harvest times. The positive control, CP, induced significant increases in micronucleated PCEs in both sexes, with means and standard errors of 3.24% ± 0.84% and 1.22% ± 0.19% for the males and females, respectively. The vehicle and positive control rates of micronucleated PCEs were within the historical control values in this laboratory (TRIAL 1). The test article, isopropanol, induced no significant increases in micronucleated polychromatic erythrocytes over the levels observed in the vehicle controls in either sex or at any of the harvest times. The positive control, CP, induced significant increases in micronucleated PCEs in both sexes, with means and standard errors of 1.56% ± 0.42% and 1.66% ± 0.39% for the males and females, respectively. The vehicle and positive control rates of micronucleated PCEs were within the historical control values in this laboratory (TRIAL 2).

Conclusions:

Interpretation of results : negative
No mutagenic activity of Propan-2-ol (Isopropyl alcohol) detected.Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/f O-isopropyl ethylthiocarbamate and there is not mutagenic activity.

Executive summary:

No mutagenic activity of Propan-2-ol (Isopropyl alcohol) detected.Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/ O-isopropyl ethylthiocarbamate and there is not mutagenic activity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

No mutagenic activity in the (Q)SAR study, In vitro mutagenicity (Ames test) alerts by ISS for Isopropyl Ethyl Thionocarbamate (IPETC)  and does not cause in vitro mutagenicity (Ames test) .This QSAR method is Relevant for in vitro (Ames test) mutagenicity endpoints.

 

No mutagenic activity of Propan-2-ol (Isopropyl alcohol) detected in the reliable study of Zeiger E, Anderson B, Haworth S, Lawlor T & Mortelmans K,1992.

Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/O-isopropyl ethylthiocarbamate and there is not mutagenic activity.

 No mutagenic activity of Propan-2-ol (Isopropyl alcohol) detected in the reliable study of Kapp, R.W., Jr, Marino, D.J., Gardiner, T.H., Masten, L.W., McKee, R.H.,, T.R., Ivett, J.L. & Young, R.R.,1993..

Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/ O-isopropyl ethylthiocarbamate and there is not mutagenic activity.

 

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

Dithiocarbamates are related compounds toThionocarbamatesand there is not mutagenic activity.

 

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

Justification for classification or non-classification

Based on the hazard assessment of IPETC/O-isopropyl ethylthiocarbamate 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 IPETC/O-isopropyl ethylthiocarbamate does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity