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Administrative data

Description of key information

- Acute oral toxicity:The LD50 value of  2324 mg/kg in rats were determined for Isopropyl Ethyl Thionocarbamate (IPETC)  as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate  and n-butanol  and propan-2-ol. This show that Reaction mass of O-isopropyl ethylthiocarbamate  and n-butanol  and propan-2-ol is of a  slightly order of acute oral toxicity . 
-Acute Dermal Toxicity: In an acute dermal toxicity study with Isopropyl Ethyl Thionocarbamate (IPETC) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol in rabbits, performed to OECD 402 test guideline, an LD50 >2000 mg/kg bw was determined. This show that Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol is not toxic for acute Dermal toxicity .
- Acute inhalation toxicity : Based on the study of Gill MW, Burleigh-Flayer HD, Strother DE, Masten LW, McKee RH, Tyler TR, Gardiner TH.1995, exposure of male and female rats to isopropanol the LC50 was > 10000 ppm.Concentrations of 10000 ppm is equal to 24.95 mg/m³ (molecular mass of 60.10 g/mol for Propan-2-ol)
Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol. Therefore, Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol .
It is concluded that the substance Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol 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:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with Isopropyl Ethyl Thionocarbamate (IPETC ) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol in male rats, performed equivalent or similar to OECD 401 test guideline, an LD50 2324 mg/kg bw was determined.
Executive summary:

Isopropyl Ethyl Thionocarbamate (IPETC) 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 Isopropyl Ethyl Thionocarbamate (IPETC) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol in male rats was established as 2324 mg/kg body weight and this show that Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol 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:
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:
Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol. Therefore, Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol .
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
6 hr exposure period instead of 4 hr, 14-day observation period was not clearly stated
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Spague-Dawley, Inc. (Indianapolis, IN)
- Age at study initiation: 9 to 11 weeks
- Housing: individually in stainless stell wire mesh cages
- Diet (e.g. ad libitum): Ground Purina Certified Rodent Chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel chambers with glass doors and windows
- Exposure chamber volume: Four approximately 1330-liter and one approximately 900-liter
- Source and rate of air: filtered air at a flow rate of approximately 14 air changes per hour
- Temperature, humidity in air chamber: recorded approximately 12 times during each exposure

TEST ATMOSPHERE
- Brief description of analytical method used: flame ionization gas chromatographic (GC) technique
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 6 h
Concentrations:
500, 1500, 5000, 10000 ppm
No. of animals per sex per dose:
25 animals/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: twice daily, beginning on the day of after exposure and continuing until sacrifice
- Frequency of observations and weighing: body weights were recored prior to exposure and during each test session
- Necropsy of survivors performed: no
Statistics:
The data for continuous, parametric variables were intercompared for the dose and control groups by use of Levene’s test for homogeneity of variances,by analysis of variance, and by pooled variance t-tests. The t-tests were used, if the analysis of variance was significant (P
Intra-session motor activity data was analyzed using a repeated measures analysis with dose as grouping factor and session time as the within subject factor. Group comparisons at each reporting epoch were made (as described above) if significant dose effects or time by dose interactions were observed.
The epsilon-adjustment procedure (Greenhouse-Geisser correction) was used in repeated measures analysis of motor activity data.
Frequency data from FOB tests was evaluated using Fisher’s exact
probability test.

All statistical tests were performed using BMDPm Statistical Software (Dixon, 1985 or Dixon, 1988). The fiducial limit of 0.05 was used as the critical level of significance for all tests.
Sex:
male/female
Dose descriptor:
other: transient, concentration-related narcosis and/or central nervous system sedation
Effect level:
5 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Sex:
male/female
Dose descriptor:
other: transient, concentration-related narcosis and/or central nervous system sedation
Effect level:
10 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 10 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Concentrations of 10000 ppm is equal to 24.95 mg/m³ (molecular mass of 60.10 g/mol for Propan-2-ol)
Sex:
male
Dose descriptor:
other: NOEL
Effect level:
500 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Based on minor decreases in motor activity in males at a concentration of 1500 ppm.The no-observed-effect level (NOEL) for this was 500 ppm isopropanol.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
24.95 mg/m³ air
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Concentrations of 10000 ppm is equal to 24.95 mg/m³ (molecular mass of 60.10 g/mol for Propan-2-ol)
Mortality:
none
Clinical signs:
other: In the 10000 ppm group, prostration, severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular tone, hypothermia, and loss of reflex function was observed 1 and 6 hours after exposure. Concentration-related decreases in mean
Body weight:
Body weight was measured at the time of behavioral testing so that any possible confounding effect that body weight might have on behavior could be assessed. Mean body weights for the five exposure groups were not statistically significantly different at any time during the study. Mean body weight tended to be lower for animals in the 10000 ppm exposure group assigned to FOB testing at the 6-hour and 24-hour post-exposure evaluations. This decrease is considered to reflect decreased food consumption during the time period when prostration and narcosis were observed.
Gross pathology:
none

Five groups of 25 Fischer 344 rats of each sex were exposed for 6 h to isopropanol vapor at 0, 500, 1500, 5000 or 10,000 ppm. Behavioral observations for 10 rats of each sex were made prior to and 1, 6, and 24 h after exposure. Motor activity was evaluated for 15 rats of each sex prior to and immediately following exposure. Exposure to isopropanol caused a spectrum of transient effects indicative of narcosis at 10,000 ppm and sedation at 5000 ppm. Prostration or severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular function, hypothermia and loss of reflex function were observed 1 and 6 h after exposure to 10,000 ppm isopropanol vapor. Similar, but less severe, alterations were observed in animals in the 5000 ppm exposure group 1 h after exposure. Exposure concentration-related decreases in motor activity were observed in males and females in the 5000 and 10,000 ppm groups and slight decreases in motor activity were observed in males in the 1500 ppm group. Animals in the 1500 and 5000 ppm exposure groups recovered from these motor activity effects within 5 h. Based on this study, exposure of male and female rats to isopropanol vapor produces transient, concentration-related narcosis and/or sedation at concentrations of 5000 and 10,000 ppm and minor decreases in motor activity in males at a concentration of 1500 ppm. The no-observed-effect level (NOEL) for this was 500 ppm isopropanol.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on this study, exposure of male and female rats to isopropanol the LC50 was > 10000 ppm.Concentrations of 10000 ppm is equal to 24.95 mg/m³ (molecular mass of 60.10 g/mol for Propan-2-ol)
Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol. Therefore, Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol .
Executive summary:

Based on this study, exposure of male and female rats to isopropanol vapor produces transient, concentration-related narcosis and/or sedation at concentrations of 5000 and 10,000 ppm and minor decreases in motor activity in males at a concentration of 1500 ppm. The no-observed-effect level (NOEL) for this was 500 ppm isopropanol.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
24.95 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with Isopropyl Ethyl Thionocarbamate (IPETC) as a main constituent, of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol in rabbits, performed to OECD 402 test guideline, an LD50 >2000 mg/kg bw was determined.
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 ) as a main constituent, of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol in rabbits was established to exceed 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

-Acute oral toxicity:The LD50 value of 2324 mg/kg in rats were determined forIsopropyl Ethyl Thionocarbamate (IPETC) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol.This show thatReaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-olis of a slightly order of acute oral toxicity .

 

-Acute Dermal Toxicity:In an acute dermal toxicity study with Isopropyl Ethyl Thionocarbamate (IPETC) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol in rabbits, performed to OECD 402 test guideline, an LD50 >2000 mg/kg bw was determined. This show thatReaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-olis not toxic foracute Dermal toxicity .

 

-Acute inhalation toxicity:Based on the study of Gill MW, Burleigh-Flayer HD, Strother DE, Masten LW, McKee RH, Tyler TR, Gardiner TH.1995, exposure of male and female rats to isopropanol the LC50 was > 10000 ppm.Concentrations of 10000 ppm is equal to 24.95 mg/m³ (molecular mass of 60.10 g/mol  for Propan-2-ol)

Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol. Therefore, Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol  and propan-2-ol .

 

It is concluded that the substance Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol meet the criteria to be classified for human health hazards for acute oral effects. 

Justification for classification or non-classification

Based on the hazard assessment of  Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol 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 Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol 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