O-isobutyl ethylthiocarbamate

Endpoint summary

Description of key information

-Acute oral toxicity:The LD50 value of 2324 mg/kg in rats were determined for O-isobutyl ethylthiocarbamate (IBETC) .This show thatReaction mass of O-isobutyl ethylthiocarbamate (IBETC) is of a slightly order of acute oral toxicity .

-Acute Dermal Toxicity: In an acute dermal toxicity study with Isopropyl Ethyl Thionocarbamate (IPETC)  performed  to OECD 402 test guideline, an LD50 >2000 mg/kg bw was determined. O-isopropyl ethylthiocarbamate (IPETC) is the similar substance as O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of O-isopropyl ethylthiocarbamate (IPETC) need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC).

-Acute inhalation toxicity: Inhalation LC50 values for vapor exposures were >6,000 ppm (18,180 mg/m3) in male and female rats.Decreases in motor activity were noted post-exposure in the 6000 ppm (18,18 0 mg/m3 ) groups but not the 3000 or 1500 ppm (9,090 or 4,550 mg/m3 )groups. No effect on motor activity was detected at the 7 and 14-day time points. No exposure-related effects were noted in the FOB assessment.

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) .

It is concluded that the substance O-isopropyl ethylthiocarbamate (IPETC)  meet the criteria to be classified for human health hazards for acute oral effects.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

The study has been performed equivalent or similar to OECD 401 guideline and according to GLP principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

Source: Ace Animals
- Age at study initiation: Not specified
- Weight at study initiation: 214 - 250 g
- Fasting period before study: 16 - 20 hours prior to dosing
- Housing: Individually in suspended cages
- Diet: Free access to Purina Rat Chow (diet #5012)
- Water: Free access to tap water.
- Acclimation period: At least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

GAVAGE METHOD: syringe and dosing needle

Frequency: single

MAXIMUM DOSE VOLUME APPLIED: The dose was based on the sample weight as calculated from the specific gravity. The test substance was administered on g/kg basis.

DOSAGE PREPARATION: The test substance was used as recieved.

Doses:

2000,2500

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Animals were deprived of food 16 - 20 hours prior to dosing. Water was available ad libitum.

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing:
Mortality/Viability/Clinical signs: 1, 4 and 24 hours post dose and once daily thereafter for 7 days for mortality.
Body weights: Body weights were recorded pretest and at termination.
- Necropsy of survivors performed: not performed.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed.

Sex:

male

Dose descriptor:

LD50

Effect level:

2 324 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Physical signs of lethargy, ataxia, chromodacryorrhea, chromorhinorrhea, dyspnea, wetness of the anagenital area and soiling of the body area were noted during the observation period.

Mortality:

No mortality occurred.

Clinical signs:

Physical signs of lethargy, ataxia, chromodacryorrhea, chromorhinorrhea, dyspnea, wetness of the anagenital area and soiling of the body area were noted during the observation period.

Body weight:

All animals gained weight during the study.

Gross pathology:

No data.

Interpretation of results:

other: sligthly toxic

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study with Isobutyl Ethyl Thionocarbamate (IBETC ) in male rats, performed equivalent or similar to OECD 401 test guideline, an LD50 2324 mg/kg bw was determined.

Executive summary:

Isobutyl Ethyl Thionocarbamate (IBETC ) was administered by oral gavage in five male rats equivalent or similar to OECD 401 guideline and according to GLP principles. No mortality occurred. Physical signs of lethargy, ataxia, chromodacryorrhea, chromorhinorrhea, dyspnea, wetness of the anagenital area and soiling of the body area were noted during the observation period. All animals gained weight during the study. The oral LD50 value of Isobutyl Ethyl Thionocarbamate (IBETC ) in male rats was established as 2324 mg/kg body weight and this show that Isobutyl Ethyl Thionocarbamate (IBETC ) is of a slightly order of acute oral toxicity according to EC regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 324 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

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:

other: 40 CFR 799 Multi-Substance Rule for the Testing of Neurotoxicity; 40 CFR Part 798.1150 Inhalation Test Guidelines; Test Guidelines 798.6050 & 798.6200 updated by Neurotoxicity Guideline 81-8, Subdivision F

Principles of method if other than guideline:

Male and female rats (10/sex) were exposed by inhalation for 6 hours to a vapor of isobutanol at 0, 1500, 3000 and 6000 ppm. The animals were observed for 14 days.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Raleigh, NC, USA
- Age at study initiation: 8 weeks
- Weight at study initiation: males: 288-388 g; females: 187-290 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 40-60 %
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Exposure Chambers: Four 2000-liter stainless steel and glass Hazelton H-2000 chambers
- Animal Housing during Exposure: Individual stainless steel wire mesh cages, positioned in one tier in the chamber
Exposure Duration: 6 hours
- Test Atmosphere Generation System: Test material was fed into a Laskin-type nebulizer mounted in a filtered supply air inlet at top of the inhalation chamber. Exposure concentrations were controlled by using an adjustable-flow valveless pump to regulate the
rate at which isobutanol was delivered to the nebulizer.
- Test Atmosphere Sampling Method: Six test atmosphere samples were drawn through a Miran 1A infrared detector calibrated for isobutanol.
Sampling Location: In the animal breathing area from a port halfway down on the chamber door
- Chamber Atmosphere Distributions: Chamber atmospheres were sampled in 2 different locations for all 3 exposure concentrations.
- Gas Chromatography Analysis: Samples of the chamber atmospheres were collected in two impingers, in series, containing methanol. The solutions were analyzed for isobutanol content using gas chromatography with a flame ionization detector.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

0, 1500, 3000, 6000 ppm (0, 4.54, 9.09, 18.18 mg/m3)

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Checks for mortality and moribundity and noteworthy signs of toxicity were made daily from the day of randomization until the day of sacrifice; weighing: day 0, day 7 and day 14
.- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

A two-way ANCOVA and Duncan’s multiple comparison test was used to determine statistical significance. The FOB evaluation was similar to methods published by Mosher (1991).

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 18 180 mg/m³ air

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: Decreases in motor activity were noted post-exposure in the 6000 ppm (18,18 0 mg/m3 )

Mortality:

1/10 male animals died at 6000 ppm. This death was attributed to an ophthalmic examination where atropine drops were applied to its eyes.All other animals survived.

Clinical signs:

other: during exposure: There was clear evidence of generalized depression of the central nervous system (animals were non-responsive to tapping on side of inhalation chambers) and labored respiration in rats during the 6 hours of exposure to 6000 and 3000 ppm o

Body weight:

Body weights of male rats in the 3000 and 6000 ppm groups were significantly lower than the male controls throughout the study. These statistically significant results are due to pretest differences and not because of exposure to the chemical.

Gross pathology:

There were no treatment-related lesions or other gross changes in the tissues and organs examined during necropsy. Enlarged, dilated, distended uteri were observed at necropsy in the low, mid, and high groups at incidences of 3/10, 1/10, and 1/10, respectively. This finding was not observed in the control group. The severity was minimal in all instances. This is a common observation and usually reflects physiologic changes related to the estrus cycle. This is further substantiated by the inverse dose response. Therefore, although histologic examination was not conducted, it appears that these observations are unassociated with treatment and reflect the normal variation expected with different stages of the estrus cycle.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Inhalation LC50 values for vapor exposures were >6,000 ppm (18180 mg/m3) in male and female rats.Decreases in motor activity were noted post-exposure in the 6000 ppm (1818 0 mg/m3 ) groups but not the 3000 or 1500 ppm (9090 or 4550 mg/m3 )groups. No effect on motor activity was detected at the 7 and 14-day time points. No exposure-related effects were noted in the FOB assessment.
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) .

Executive summary:

Male and female rats exposed to atmospheric vapor levels of 0, 1500, 3000, or 6000 ppm (0, 4550, 9090, 18180 mg/m3) for six hours were evaluated in a neurobehavioral battery (motor activity determination and a functional observational battery) within two hours post-exposure. Hypoactivity and diminished response to a startle reflex (during the inhalation exposure) was observed during exposure for the 3000 and 6000 ppm (9090 and 18180 mg/m3) exposures. Decreases in motor activity were noted post-exposure in the 6000 ppm (1818 0 mg/m3 ) groups but not the 3000 or 1500 ppm (9090 or 4550 mg/m3 )groups. No effect on motor activity was detected at the 7 and 14-day time points. No exposure-related effects were noted in the FOB assessment. Inhalation LC50 values for vapor exposures were >6,000 ppm (18180 mg/m3) in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

18 180 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

O-isopropyl ethylthiocarbamate (IPETC) is the similar substance as O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of O-isopropyl ethylthiocarbamate (IPETC) need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC).

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: New Zealand Albino rabbits

Sex:

male

Details on test animals or test system and environmental conditions:

- Source: Ace Animals
- Age at study initiation: Not specified
- Weight at study initiation: 2.2 - 2.5 kg
- Housing: Individually in suspended cages.
- Diet: Free access to Purina Rabbit Chow (Diet #5321)
- Water: Free access to tap water.
- Acclimation period: At least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled
- Humidity (%): no data available
- Air changes (per hr): no data available
- Photoperiod (hrs dark / hrs light): no data available.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Prior to application of the test substance, the dorsal area of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact.

The test substance was covered with a gauze patch which was secured with non-irritating adhesive tape. The torso was wrapped with plastic which was held in place with non-irritating tape.

Frequency: Single dosage, on Day 1.

Washing: No, following application, wrappings were removed and the sites were wiped.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

DOSAGE PREPARATION: The test substance was used as received, measured by syringe and applied to the prepared site.

Duration of observation period following administration: 7 days
- Frequency of observations and weighing:
Mortality/Viability/Clinical signs: 1, 4 and 24 hours post dose and once daily thereafter for 7 days for mortality.
Body weights: Body weights were recorded pretest and at termination.
- Necropsy of survivors performed: Not performed.
- Other examinations performed: none.

Statistics:

None.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

One animal exhibited yellow nasal discharge on the day of dosing and on day 1. At all other times, all animals appeared normal during the observation period.

Body weight:

Body weight changes were normal.

Gross pathology:

No data.

A single dose of 2 000 mg/kg of the notified chemical was administered by semi-occlusive application to the shaved skin of New Zealand Albino rabbits (5 males) for 24 hours. The animals were observed at 1, 4 and 24 hours after dosing and subsequently once daily for 7 days after removal of the bandage. No deaths were noted during the study. All animals showed expected gain in body weight during the study. One animal exhibited yellow nasal discharge up to day one. All animals showed slight to moderate erythema and oedema. Necropsy findings were not recorded in the study. The results of this study indicate a dermal LD50 of > 2 000 mg/kg for the notified chemical in male rabbits.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity study with Isopropyl Ethyl Thionocarbamate (IPETC) performed to OECD 402 test guideline, an LD50 >2000 mg/kg bw was determined.
O-isopropyl ethylthiocarbamate (IPETC) is the similar substance as O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of O-isopropyl ethylthiocarbamate (IPETC) need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC).

Executive summary:

Isopropyl Ethyl Thionocarbamate (IPETC ) was administered to five male New Zealand Albino rabbits by a single dermal occlusive application at 2000 mg/kg bw equivalent to OECD 402 guideline and according to GLP principles. No mortality occurred. One animal exhibited yellow nasal discharge on the day of dosing and on day 1. At all other times, all animals appeared normal during the observation period. Body weight changes were normal.

The dermal LD50 value of Isopropyl Ethyl Thionocarbamate (IPETC ) in rabbits was established to exceed 2000 mg/kg body weight. O-isopropyl ethylthiocarbamate (IPETC) is the similar substance as O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of O-isopropyl ethylthiocarbamate (IPETC) need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99) and according to the criteria described in Directive 67/548 and in the CLP Regulation:

 

      

Directive 67/548

Very Toxic (T+) R28: Very toxic if swallowed R27: Very toxic in contact with skin R26: Very toxic by inhalation R39/26 R39/27 R39/28: Dangerous of very serious irreversible effects Toxic (T):  R25: Toxic if swallowed R24: Toxic in contact with skin R23: Toxic by inhalation R39/23 R39/24 R39/25: Danger of very serious irreversible effects Harmful (Xn): R22: Harmful if swallowed R21: Harmful in contact with skin R20: Harmful by inhalation R65: Harmful may cause lung damage if swallowed R21/22 Harmful; Harmful in contact with skin and if swallowed. R68/20 R68/21 R68/22: Possible risk of irreversible effects Other toxicological properties R67: Vapours may cause drowsiness and dizziness

CLP

H300 Acute Tox. 2 Fatal if swallowed H310 Acute Tox. 1 Fatal in contact with skin H330 Acute Tox. 2 Fatal if inhaled H370 STOT SE 1 H301 Acute Tox. 3 Toxic if swallowed H311 Acute Tox. 3 Toxic in contact with skin H331 Acute Tox. 3 Toxic if inhaled H370 STOT SE 1 H302 Acute Tox. 4 Harmful if swallowed H312 Acute Tox. 4 Harmful in contact with skin H332 Acute Tox. 4 Harmful if inhaled H304 Asp. Tox. 1 H371 STOT SE 2 (May cause damage to organs (or state all organsaffected if known) (state route of exposure if it is conclusively proventhat no other routes of exposure cause the hazard) Other toxicological properties H336 STOT SE 3 May cause drowsiness or dizziness

 

 

It is concluded that the substance O-isobutyl ethylthiocarbamate (IBETC) meet the criteria to be classified for human health hazards for acute oral effects:

R22: Harmful if swallowed

H302 Acute Tox. 4 Harmful if swallowed