O-isobutyl ethylthiocarbamate

Endpoint summary

Description of key information

Eye irritation

-Instillation of 0.1 ml of the substance into rabbit eyes produced severe ocular irritation. Minor conjunctival redness was still evident at 21 days. Minor Moderate to severe irritation was produced from the application of 0.01 ml.

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) .

The eye irritation potential of the substance was examined in rabbits. Instillation of 0.1 ml into rabbit eyes produced severe ocular irritation. Minor conjunctival redness was still evident at 21 days. Moderate to severe irritation was produced from the application of 0.01 ml.

Based on the descriptions of the lesions it is considered that O-isobutyl ethylthiocarbamate (IBETC) is classifiable as  irritant according to EU criteria

Skin irritation

The acute dermal irritation of the substance was examined in a 4 -hour exposure. Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.

Based on the descriptions of the lesions it is considered O-isobutyl ethylthiocarbamate (IBETC) is classifiable as  moderately irritant according to EU criteria.

 

Respiratory irritation.

Due to the absence of chemical groups or other structural alerts this substance is not considered to exhibit an high hazard potential. O-isobutyl ethylthiocarbamate (IBETC) is  of low priority for further work based on a low hazard potential.is  of low priority for further work based on a low hazard potential.  Therefore testing for Respiratory Respiratory irritation does not need to be performed.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

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:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Male and female New Zealand White rabbits were received from Hazleton Research Products, Inc. (Denver, PA). The strain and species were selected because of their availability and existing historical data. Rabbits were ordered to be between 2.0 and 2.3 kg (designated by the supplier to be approximately 12 to 14 weeks of age). The females were nulliparous and nonpregnant. Periodically, a Clinical Veterinarian examined rabbits for any signs of health deficiencies. Within 1 or 2 days of receipt, all animals were assigned a unique number which was marked on the animal cage card. The rabbit number was also marked in indelible ink on 1 ear at the time of dosing. The rabbits were housed individually in cages with wire floors (approximately 61.0 x 46.0 x 36.0 cm.). DACBQ (Deotized Animal Cage Board; Shepherd Specialty Papers, Inc.) was placed under each cage and changed regularly. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 0500 to 1700 hours for the light phase). Temperature and relative humidity were recorded (Cole-Parmer Hygrothermograph Seven-Day Continuous Recorder, Model No. 8368-00, Cole-Parmer Instrument Co., Chicago, IL). Temperature was routinely maintained at 61-70°F during the test period; relative humidity was routinely maintained at 40-70%. Any minor exceptions to these specified ranges were noted in the raw data.Tap water (Municipal Authority of Westmoreland County, Greensburg, PA) was available ad libitum (except during dosing) and was delivered by an automatic watering system with demand control valves mounted on each rack. Water analyses were provided by the supplier, Halliburton NUS Environmental Laboratories, Materials Engineering & Testing Company, and Lancaster Laboratories, Inc. at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. As available, water analysis reports were reviewed by the Study Director. AGWAYe PROLABe Animal Diet High Fiber Rabbit (Agway Inc.) was available ad libitum except during the actual dosing period. No analyses of chemical composition and possible contaminants of the feed were conducted by the supplier.Animal AcclimationThe animals were acclimated for at least 5 days before dosing. Detailed clinical observations were conducted twice, at the time of receipt and during animal identification and/or dosing. In addition, rabbits were examined and weighed twice prior to dosing. Cage-side observations and mortality checks were conducted at least once daily. Animals considered unacceptable for the study, based on the clinical signs or body weights (rabbits), were rejected for use on this study.Study OrganizationThe animals were weighed and inspected for health on the day of the test. Only those exhibiting a healthy state were used. Healthy animals appeared alert, active and well groomed, with no evidence of discharge, diarrhea, breathing difficulties or locomotor abnormalities. A BRRC veterinarian was available for consultation regarding any animal health concerns. Animals were randomly assigned to cages and were designated for dosing according to need and availability.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

Readings were made at 1, 24, 48 and 72 hours and at 7 and 14 days, after the end of the contact period.

Number of animals:

3 males and 3 females

Details on study design:

The fur was removed from the dorsal area of the trunk of each rabbit using veterinary clippers a few days before dosing and the dose area was trimmed carefully (avoiding skin abrasion), as necessary, up to the day before application of the test substance. A 1-inch square gauze patch was placed over 1 intact (nonabraded) site/rabbit and secured by adhesive tape. A volume of 0.5 ml was then applied under the patch. Polyethylene sheeting was placed loosely around the trunk and secured. The animal was placed in a restraining device for the 4-hour contact period after which the coverings and as much excess test substance as possible were removed.The test substance was applied to each of 6 rabbits (3 males, 3 females). Readings were made at 1, 24, 48 and 72 hours and at 7 and 14 days, after the end of the contact period according to the method of Draize, 1959. All rabbits were sacrificed at 14 days (ear vein injection using Euthanasia-6 Solution).ReferenceDraize, J. H. (1959). The Appraisal of Chemicals in Foods, Drugs and Cosmetics. Tbe Association of Food and Drug Officials of the United States.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1.2

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Maximum score observed. One animal had a score of 1 on day 14.

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Maximum score observed. One animal had a score of 1 on day 14.

Irritant / corrosive response data:

Application of 0.5 ml of isobutanol to covered rabbit skin for a 4-hour contact period produced minor to moderate erythema and edema on 6 of 6 rabbits within 1 day. (Maximum score noted on any animal for erythema or edema was 2). One rabbit had a light brown discoloration on the dose site at 1 hour. Superficial necrosis developed on this animal by 1 day; another rabbit had superficial necrosis at 7 days. Ecchymoses were apparent on 1 animal within 1 day. At 7 days, fissuring was observed on 1 animal. Four rabbits had desquamation at this time. By 14 days, alopecia was observed on 2 rabbits. Erythema and edema subsided on 5 of 6 rabbits within 14 days; minor erythema and edema persisted on 1 rabbit. Two rabbits had a normal appearance at this time.

Other effects:

No additional information available.

Interpretation of results:

other: moderately irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.

Executive summary:

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) .

The acute dermal irritation was examined in a 4 -hour exposure. Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: A. Smith, England
- Age at study initiation: ca. 12 weeks
- Weight at study initiation: 2.6 kg

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

n.a.

Observation period (in vivo):

24 h

Number of animals or in vitro replicates:

1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24 h

Score:

3

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24 h

Score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 h

Score:

3

Reversibility:

not reversible

Remarks on result:

other: Necrosis and partial destruction of nictitating membrane.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24 h

Score:

4

Reversibility:

not reversible

Other effects:

Due to the severity of the response only one animal was exposed to the test substance and the study was terminated on humane grounds 24 h after instillation.

Interpretation of results:

other: irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Instillation of 0.1 ml of ziram into rabbit eyes produced severe ocular irritation.
Dithiocarbamates are related compounds to Thionocarbamate.

Reference 2

Endpoint:

eye irritation: in vivo

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Male and female New Zealand White rabbits were received from Hazleton Research Products, Inc. (Denver, PA). The strain and species were selected because of their availability and existing historical data. Rabbits were ordered to be between 2.0 and 2.3 kg (designated by the supplier to be approximately 12 to 14 weeks of age). The females were nulliparous and nonpregnant. Periodically, a Clinical Veterinarian examined rabbits for any signs of health deficiencies. Within 1 or 2 days of receipt, all animals were assigned a unique number which was marked on the animal cage card. The rabbit number was also marked in indelible ink on 1 ear at the time of dosing. The rabbits were housed individually in cages with wire floors (approximately 61.0 x 46.0 x 36.0 cm.). DACBQ (Deotized Animal Cage Board; Shepherd Specialty Papers, Inc.) was placed under each cage and changed regularly. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 0500 to 1700 hours for the light phase). Temperature and relative humidity were recorded (Cole-Parmer Hygrothermograph Seven-Day Continuous Recorder, Model No. 8368-00, Cole-Parmer Instrument Co., Chicago, IL). Temperature was routinely maintained at 61-70°F during the test period; relative humidity was routinely maintained at 40-70%. Any minor exceptions to these specified ranges were noted in the raw data.Tap water (Municipal Authority of Westmoreland County, Greensburg, PA) was available ad libitum (except during dosing) and was delivered by an automatic watering system with demand control valves mounted on each rack. Water analyses were provided by the supplier, Halliburton NUS Environmental Laboratories, Materials Engineering & Testing Company, and Lancaster Laboratories, Inc. at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. As available, water analysis reports were reviewed by the Study Director. AGWAYe PROLABe Animal Diet High Fiber Rabbit (Agway Inc.) was available ad libitum except during the actual dosing period. No analyses of chemical composition and possible contaminants of the feed were conducted by the supplier.Animal AcclimationThe animals were acclimated for at least 5 days before dosing. Detailed clinical observations were conducted twice, at the time of receipt and during animal identification and/or dosing. In addition, rabbits were examined and weighed twice prior to dosing. Cage-side observations and mortality checks were conducted at least once daily. Animals considered unacceptable for the study, based on the clinical signs or body weights (rabbits), were rejected for use on this study.Study OrganizationThe animals were weighed and inspected for health on the day of the test. Only those exhibiting a healthy state were used. Healthy animals appeared alert, active and well groomed, with no evidence of discharge, diarrhea, breathing difficulties or locomotor abnormalities. A BRRC veterinarian was available for consultation regarding any animal health concerns. Animals were randomly assigned to cages and were designated for dosing according to need and availability.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Initial study0.1 mlFollow up study0.01 ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

Initial study 1, 24, 48, 52.5 hours and at 7, 9, 14, 15 and 21 days following instillation.Follow up study1, 24, 48 and 72 hours and at 7, 10 and 14 days

Number of animals or in vitro replicates:

Initial study1 male and 1 femaleFollow up study2 males and 2 females

Details on study design:

Both eyes of each rabbit to be dosed were examined, using fluorescein stain, within 24 hours before application. If any preexisting eye injury wasapparent, the rabbit was rejected for use in the test. A volume of 0.1 ml of test substance was placed into the conjunctival sac of 1 eye/rabbit. The other eye of each animal served as the control.A total of 2 rabbits (1 male and 1 female) were first dosed because of the potential for the test substance to produce severe ocular irritation. Eye examinations were made at 1, 24, 48, 52.5 hours and at 7, 9, 14, 15 and 21 days following instillation. Readings were not made at 72 hours because of a lost workday resulting from severe weather conditions. However, in anticipation of the lost workday, an additional reading was made in the afternoon of the second day following dose administration. Fluorescein staining was performed at 1 day and each subsequent examination day. Grading and scoring were performed by the system of Draize (1959). All rabbits were sacrificed by ear vein injection (Euthanasia-6 Solution) at 21 days.Because severe ocular irritancy resulted from a dose of 0.1 ml, an additional 4 rabbits (2 males, 2 females) were dosed with 0.01 ml for comparison. These rabbits were dosed as described above except the dose was applied directly onto the cornea. Eye examinations were made at 1, 24, 48 and 72 hours and at 7, 10 and 14 days (Draize, 1959). All 4 animals were sacrificed at 14 days (ear vein injection using Euthanasia-6 Solution).ReferenceDraize, J. H. (1959). The Appraisal of Chemicals in Foods, Drugs and Cosmetics. Tbe Association of Food and Drug Officials of the United States.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

2.3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Minor conjunctival redness was still evident at 21 days.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1.8

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

A volume of 0.1 ml of test substance instilled into rabbit eyes produced minor to moderate corneal injury in 2 of 2 rabbits. Iritis and severe conjunctival irritation were also apparent in both rabbits. One rabbit developed severe conjunctival swelling within 1 hour. At 24 hours, both rabbits had hemorrhages of the nictitating membrane. One animal also had a purulent ocular discharge. Within 7 days, corneal vascularization developed on 1 rabbit. Except for alopecia, 1 rabbit had a normal ocular appearance at 9 through 15 days. Minor conjunctival redness was again evident in this animal at 21 days. Minor conjunctival redness persisted in the other rabbit at this time.Following the application of 0.01 ml of isobutanol onto 4 rabbit eyes, minor corneal injury was observed in 2. Iritis and moderate to severe conjunctival irritation were apparent in all 4 rabbit eyes. At 48 and 72 hours, 2 rabbits had hemorrhages of the nictitating membrane and/or sclera. One rabbit had a normal ocular appearance at 72 hours and another 2 rabbit eyes were healed at 7 days. All 4 rabbits had a normal ocular appearance by 14 days.

Other effects:

Both animals dosed with 0.1 ml had alopecia of the periocular area (with a small scab on 1) by 9 days.

Interpretation of results:

other: irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Instillation of 0.1 ml of the substance into rabbit eyes produced severe ocular irritation. Minor conjunctival redness was still evident at 21 days. Minor Moderate to severe irritation was produced from the application of 0.01 ml.

Executive summary:

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) .

The eye irritation potential of the substance was examined in rabbits. Instillation of 0.1 ml into rabbit eyes produced severe ocular irritation. Minor conjunctival redness was still evident at 21 days. Moderate to severe irritation was produced from the application of 0.01 ml.

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Respiratory irritation.

 

Due to the absence of chemical groups or other structural alerts this substance is not considered to exhibit an high hazard potential. O-isobutyl ethylthiocarbamate (IBETC) is of low priority for further work based on a low hazard potential.is of low priority for further work based on a low hazard potential. Therefore testing for Respiratory Respiratory irritation does not need to be performed.  

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

Skin Corrosivity C R35 Causes severe burns R34 Causes burns Skin Irritation Xi R38 Irritating to skin R43 May cause sensitization by skin contact Eye Irritation (Ocular Lesions) Xi R36 Irritating to eyes R36/38 - Irritating to eyes and skin R37 irritating to respiratory system R41 Risk of serious damage to eyes

CLP

Skin Corrosivity H314 Skin Corr 1A Causes severe skin burns and eye damage H314 Skin Corr 1B Causes severe skin burns and eye damage Skin Irritation H315 Skin Irrit. 2 Causes skin irritation H317 Skin Sens. 1 May cause an allergic skin reaction Eye Irritation (Ocular Lesions) Xi H319 Eye Irrit. 2 Causes serious eye irritation H318 Eye Dam. 1 Causes serious eye damage H335 STOT SE 3 May cause respiratory irritation

 

 

 It is concluded that the substance  O-isobutyl ethylthiocarbamate (IBETC) meet the criteria to be classified for human health hazards for Dermal-local effect:  R36/38 - Irritating to eyes and skin, H315 Skin Irrit. 2 Causes skin irritation, H319 Eye Irrit. 2 Causes serious eye irritation

It is concluded that the substanceO-isobutyl ethylthiocarbamate(IBETC)does not meet the criteria to be classified for human health hazards for respiratory irritation