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Neurotoxicity

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Description of key information

There are conclusive but not suffcient data for the classification of substance Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol   with regard to Neurotoxicity.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Link to relevant study records
Reference
Endpoint:
neurotoxicity: short-term oral
Type of information:
experimental study
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:
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:
according to guideline
Guideline:
OECD Guideline 426 (Developmental Neurotoxicity Study)
Deviations:
no
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. Raleigh, NC
- Age at study initiation: 9 weeks on gestation day 0
- Weight at study initiation: 174-197 g on gestation day 0
- Fasting period before study: None
- Housing: singly caged in solid bottom polycarbonate cages with stainless steel wire lids
- Diet (e.g. ad libitum): 5002 Purina certified rodent chow was available ad libitum
- Water (e.g. ad libitum): tap water in polycarbonate bottles was available ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-75 (20 - 24ºC)
- Humidity (%): 40-70
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS

Vehicle was deionized/distilled water
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Not required
Duration of treatment / exposure:
Administered from day 6 of gestation to day 21 post natal
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
200, 700, or 1200 mg/kg body weight/day
Basis:
actual ingested
No. of animals per sex per dose:
64 females/group
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Review from 4 previous studies
- Rationale for animal assignment (if not random): sperm postive female rats were assigned to treatment groups by a stratified randomization method designed to provide uniformed mean body wieghts accross dose groups
Observations and clinical examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily on gestation days 0-5 and twice daily through dosing period gestation day 6 to post natal day 21


BODY WEIGHT: Yes
- Time schedule for examinations: maternal body weights were measured on gestation days 0, 6, 9, 12, 15, 18, 20 and on post natal days 0, 4, 7, 13, 17, and 21


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not applicable


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: No
Specific biochemical examinations:
NEUROPATHY TARGET ESTERASE (NTE) ACTIVITY: No

CHOLINESTERASE ACTIVITY: No

Other; one male/female pair from each dose group was sacrified on post natal day 22 for neuropathological assessment and measurement of brain weights
Neurobehavioural examinations performed and frequency:
FUNCTIONAL OBSERVATIONAL BATTERY: No

MOTOR ACTIVITY: Yes
- Replicates used: one male/female pair from each litter was conducted on days 13, 17, 21, 47, and 58
- Type of equipment used: Figure 8 maze
- Length of session; one hour period


AUDITORY STARTLE REFLEX HABITUATION: Yes
- Number of animals: one male/female pair from each litter was conducted on days 22 and 60
- Same offspring evaluated at each preweaning time point: yes
- Exact age: Not reported
- Type of equipment used: Not reported
- Environmental conditions: Not reported
- Number of trials performed: 2
- Length (msec) and intensity (dB) of sound: 50 ms and 120 dB
- Length of interval between trials: 50 times in a session (five contiguous 10 trial blocks)

Other; Active avoidance test
- Number of animals: one male/female pair from each litter was conducted on days 60-64
- Each animal was exposed to a continous light and sound for 10 seconds following by a mild electric current delivered to a foot grid for 30 seconds.
Sacrifice and (histo)pathology:
MATERNAL ANIMALS
- Time point of sacrifice or discard without postmortem examination: post natal day 22
- Method of sacrifice: asphyxiation with CO2
- Postmortem evaluations;
- Necropsy: Yes
- Brain weight: Yes
- Other organ weights: Yes
- Histopathology: Yes

OFFSPRING
- Time point of sacrifice of offspring selected for brain weight or neuropathological evaluation: postnatal day 22
- Description of postmortem examinations:
- At postnatal day 22 one male and one female per group were selected for brain weight measurements
- The brains from these pups/sex/group were immersion fixed and embedded in paraffin, blocked, sectioned, and stained with hematoxylin and eosin.
- Histopathological examination was performed on tissues from control and high-dose pups.
- On postnatal day 4, pups that were culled were euthanized and necropsied.
- On postnatal day 68, the remaining animals were necropsied.
Other examinations:
None
Positive control:
No postive control was used
Statistics:
A combination of categorical, analysis of variance, survival time, and repeated measures techniques were used.
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Clinical biochemistry findings:
not examined
Behaviour (functional findings):
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Other effects:
no effects observed
Description (incidence and severity):
Migrated information from 'Further observations for developmental neurotoxicity study'



Details on results (for developmental neurotoxicity):OTHER FINDINGS
- no significant findings in the motor activity test, startle test, and the active avoidance test. (migrated information)
Details on results:
One maternal animal died in the 1200 dose group on post natal day 15.
The mean food consumption of females in the 700 dose group was significantly increased but only on post natal days 0-3.
Dose descriptor:
NOAEL
Effect level:
700 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: based on the death of 1 animal in the high-dose group
Remarks on result:
other: Generation: maternal (migrated information)
Dose descriptor:
NOAEL
Effect level:
1 200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects
Remarks on result:
other: Generation: offspring (migrated information)
Conclusions:
NOEL Maternal Toxicity = 700 mg/kg bw/day
There was no evidence of developmental neurotoxicity associated with isopropanol exposure as high as 1200 mg/kg/day (NOEL Developmental Neurotoxicity = 1200 mg/kg bw/day) .
Propan-2-ol (Isopropyl alcohol) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate (85%-98%) and n-butanol (1%-10%) and propan-2-ol (1%-5%) and need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol .ol .
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 200 mg/kg bw/day
Study duration:
subacute
Species:
rat

Effect on neurotoxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
neurotoxicity: short-term oral
Type of information:
experimental study
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:
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:
according to guideline
Guideline:
OECD Guideline 426 (Developmental Neurotoxicity Study)
Deviations:
no
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. Raleigh, NC
- Age at study initiation: 9 weeks on gestation day 0
- Weight at study initiation: 174-197 g on gestation day 0
- Fasting period before study: None
- Housing: singly caged in solid bottom polycarbonate cages with stainless steel wire lids
- Diet (e.g. ad libitum): 5002 Purina certified rodent chow was available ad libitum
- Water (e.g. ad libitum): tap water in polycarbonate bottles was available ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-75 (20 - 24ºC)
- Humidity (%): 40-70
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS

Vehicle was deionized/distilled water
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Not required
Duration of treatment / exposure:
Administered from day 6 of gestation to day 21 post natal
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
200, 700, or 1200 mg/kg body weight/day
Basis:
actual ingested
No. of animals per sex per dose:
64 females/group
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Review from 4 previous studies
- Rationale for animal assignment (if not random): sperm postive female rats were assigned to treatment groups by a stratified randomization method designed to provide uniformed mean body wieghts accross dose groups
Observations and clinical examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily on gestation days 0-5 and twice daily through dosing period gestation day 6 to post natal day 21


BODY WEIGHT: Yes
- Time schedule for examinations: maternal body weights were measured on gestation days 0, 6, 9, 12, 15, 18, 20 and on post natal days 0, 4, 7, 13, 17, and 21


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not applicable


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: No
Specific biochemical examinations:
NEUROPATHY TARGET ESTERASE (NTE) ACTIVITY: No

CHOLINESTERASE ACTIVITY: No

Other; one male/female pair from each dose group was sacrified on post natal day 22 for neuropathological assessment and measurement of brain weights
Neurobehavioural examinations performed and frequency:
FUNCTIONAL OBSERVATIONAL BATTERY: No

MOTOR ACTIVITY: Yes
- Replicates used: one male/female pair from each litter was conducted on days 13, 17, 21, 47, and 58
- Type of equipment used: Figure 8 maze
- Length of session; one hour period


AUDITORY STARTLE REFLEX HABITUATION: Yes
- Number of animals: one male/female pair from each litter was conducted on days 22 and 60
- Same offspring evaluated at each preweaning time point: yes
- Exact age: Not reported
- Type of equipment used: Not reported
- Environmental conditions: Not reported
- Number of trials performed: 2
- Length (msec) and intensity (dB) of sound: 50 ms and 120 dB
- Length of interval between trials: 50 times in a session (five contiguous 10 trial blocks)

Other; Active avoidance test
- Number of animals: one male/female pair from each litter was conducted on days 60-64
- Each animal was exposed to a continous light and sound for 10 seconds following by a mild electric current delivered to a foot grid for 30 seconds.
Sacrifice and (histo)pathology:
MATERNAL ANIMALS
- Time point of sacrifice or discard without postmortem examination: post natal day 22
- Method of sacrifice: asphyxiation with CO2
- Postmortem evaluations;
- Necropsy: Yes
- Brain weight: Yes
- Other organ weights: Yes
- Histopathology: Yes

OFFSPRING
- Time point of sacrifice of offspring selected for brain weight or neuropathological evaluation: postnatal day 22
- Description of postmortem examinations:
- At postnatal day 22 one male and one female per group were selected for brain weight measurements
- The brains from these pups/sex/group were immersion fixed and embedded in paraffin, blocked, sectioned, and stained with hematoxylin and eosin.
- Histopathological examination was performed on tissues from control and high-dose pups.
- On postnatal day 4, pups that were culled were euthanized and necropsied.
- On postnatal day 68, the remaining animals were necropsied.
Other examinations:
None
Positive control:
No postive control was used
Statistics:
A combination of categorical, analysis of variance, survival time, and repeated measures techniques were used.
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Clinical biochemistry findings:
not examined
Behaviour (functional findings):
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Other effects:
no effects observed
Description (incidence and severity):
Migrated information from 'Further observations for developmental neurotoxicity study'



Details on results (for developmental neurotoxicity):OTHER FINDINGS
- no significant findings in the motor activity test, startle test, and the active avoidance test. (migrated information)
Details on results:
One maternal animal died in the 1200 dose group on post natal day 15.
The mean food consumption of females in the 700 dose group was significantly increased but only on post natal days 0-3.
Dose descriptor:
NOAEL
Effect level:
700 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: based on the death of 1 animal in the high-dose group
Remarks on result:
other: Generation: maternal (migrated information)
Dose descriptor:
NOAEL
Effect level:
1 200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects
Remarks on result:
other: Generation: offspring (migrated information)
Conclusions:
NOEL Maternal Toxicity = 700 mg/kg bw/day
There was no evidence of developmental neurotoxicity associated with isopropanol exposure as high as 1200 mg/kg/day (NOEL Developmental Neurotoxicity = 1200 mg/kg bw/day) .
Propan-2-ol (Isopropyl alcohol) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate (85%-98%) and n-butanol (1%-10%) and propan-2-ol (1%-5%) and need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol .ol .
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
52.17 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat 1200 mg/kg bw/day
÷1.15m3/kgbw
÷20m3/rat
NOAECrat 52.17 mg/m3

Effect on neurotoxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
neurotoxicity: short-term oral
Type of information:
experimental study
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:
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:
according to guideline
Guideline:
OECD Guideline 426 (Developmental Neurotoxicity Study)
Deviations:
no
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. Raleigh, NC
- Age at study initiation: 9 weeks on gestation day 0
- Weight at study initiation: 174-197 g on gestation day 0
- Fasting period before study: None
- Housing: singly caged in solid bottom polycarbonate cages with stainless steel wire lids
- Diet (e.g. ad libitum): 5002 Purina certified rodent chow was available ad libitum
- Water (e.g. ad libitum): tap water in polycarbonate bottles was available ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-75 (20 - 24ºC)
- Humidity (%): 40-70
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS

Vehicle was deionized/distilled water
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Not required
Duration of treatment / exposure:
Administered from day 6 of gestation to day 21 post natal
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
200, 700, or 1200 mg/kg body weight/day
Basis:
actual ingested
No. of animals per sex per dose:
64 females/group
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Review from 4 previous studies
- Rationale for animal assignment (if not random): sperm postive female rats were assigned to treatment groups by a stratified randomization method designed to provide uniformed mean body wieghts accross dose groups
Observations and clinical examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily on gestation days 0-5 and twice daily through dosing period gestation day 6 to post natal day 21


BODY WEIGHT: Yes
- Time schedule for examinations: maternal body weights were measured on gestation days 0, 6, 9, 12, 15, 18, 20 and on post natal days 0, 4, 7, 13, 17, and 21


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not applicable


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: No
Specific biochemical examinations:
NEUROPATHY TARGET ESTERASE (NTE) ACTIVITY: No

CHOLINESTERASE ACTIVITY: No

Other; one male/female pair from each dose group was sacrified on post natal day 22 for neuropathological assessment and measurement of brain weights
Neurobehavioural examinations performed and frequency:
FUNCTIONAL OBSERVATIONAL BATTERY: No

MOTOR ACTIVITY: Yes
- Replicates used: one male/female pair from each litter was conducted on days 13, 17, 21, 47, and 58
- Type of equipment used: Figure 8 maze
- Length of session; one hour period


AUDITORY STARTLE REFLEX HABITUATION: Yes
- Number of animals: one male/female pair from each litter was conducted on days 22 and 60
- Same offspring evaluated at each preweaning time point: yes
- Exact age: Not reported
- Type of equipment used: Not reported
- Environmental conditions: Not reported
- Number of trials performed: 2
- Length (msec) and intensity (dB) of sound: 50 ms and 120 dB
- Length of interval between trials: 50 times in a session (five contiguous 10 trial blocks)

Other; Active avoidance test
- Number of animals: one male/female pair from each litter was conducted on days 60-64
- Each animal was exposed to a continous light and sound for 10 seconds following by a mild electric current delivered to a foot grid for 30 seconds.
Sacrifice and (histo)pathology:
MATERNAL ANIMALS
- Time point of sacrifice or discard without postmortem examination: post natal day 22
- Method of sacrifice: asphyxiation with CO2
- Postmortem evaluations;
- Necropsy: Yes
- Brain weight: Yes
- Other organ weights: Yes
- Histopathology: Yes

OFFSPRING
- Time point of sacrifice of offspring selected for brain weight or neuropathological evaluation: postnatal day 22
- Description of postmortem examinations:
- At postnatal day 22 one male and one female per group were selected for brain weight measurements
- The brains from these pups/sex/group were immersion fixed and embedded in paraffin, blocked, sectioned, and stained with hematoxylin and eosin.
- Histopathological examination was performed on tissues from control and high-dose pups.
- On postnatal day 4, pups that were culled were euthanized and necropsied.
- On postnatal day 68, the remaining animals were necropsied.
Other examinations:
None
Positive control:
No postive control was used
Statistics:
A combination of categorical, analysis of variance, survival time, and repeated measures techniques were used.
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Clinical biochemistry findings:
not examined
Behaviour (functional findings):
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Other effects:
no effects observed
Description (incidence and severity):
Migrated information from 'Further observations for developmental neurotoxicity study'



Details on results (for developmental neurotoxicity):OTHER FINDINGS
- no significant findings in the motor activity test, startle test, and the active avoidance test. (migrated information)
Details on results:
One maternal animal died in the 1200 dose group on post natal day 15.
The mean food consumption of females in the 700 dose group was significantly increased but only on post natal days 0-3.
Dose descriptor:
NOAEL
Effect level:
700 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: based on the death of 1 animal in the high-dose group
Remarks on result:
other: Generation: maternal (migrated information)
Dose descriptor:
NOAEL
Effect level:
1 200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects
Remarks on result:
other: Generation: offspring (migrated information)
Conclusions:
NOEL Maternal Toxicity = 700 mg/kg bw/day
There was no evidence of developmental neurotoxicity associated with isopropanol exposure as high as 1200 mg/kg/day (NOEL Developmental Neurotoxicity = 1200 mg/kg bw/day) .
Propan-2-ol (Isopropyl alcohol) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate (85%-98%) and n-butanol (1%-10%) and propan-2-ol (1%-5%) and need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol .ol .
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
30 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
1200 mg/kg bw/day x 0.025 kg =
NOAELrat = 30 mg/kg bw/day


Additional information

Oral exposure:

There was no evidence of developmental neurotoxicity associated with isopropanol exposure as high as 1200 mg/kg/day (NOEL Developmental Neurotoxicity = 1200 mg/kg bw/day) .Propan-2-ol (Isopropyl alcohol) as a main constituent of Reaction mass of O-isopropyl ethylthiocarbamate (85%-98%) and n-butanol (1%-10%) and propan-2-ol (1%-5%) and need to be considered in the assessment of Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol  and propan-2-ol .ol .

 

Inhalation exposure:

 

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat             1200 mg/kg bw/day

÷1.15m3/kgbw

÷20m3/rat

NOAECrat     52.17 mg/m3

 

 

 

Dermal exposure:

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

1200 mg/kg bw/day x 0.025 kg =                  

 NOAELrat  = 30 mg/kg bw/day

 

 

 

 

 

 

 

Justification for classification or non-classification

There are conclusive but not suffcient data for the classification of substance Reaction mass of O-isopropyl ethylthiocarbamate and n-butanol and propan-2-ol  with regard to Neurotoxicity.