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EC number: 470-080-3 | CAS number: -
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 97.9 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 18
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 13.9 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 72
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
Workers - Hazard for the eyes
Additional information - workers
Acute/short-term exposure - systemic effects
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified.
Referring to the available data on acute toxicity, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate displays no acute toxicity up to 5000 mg/kg bw determined in rats for the oral and dermal route. No experimental data for the inhalation route are available. Therefore, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate is not subject to classification for acute toxicity according to Directive 67/548/EEC and Regulation No 1272/2008, and consequently the derivation of worker DNELs for acute/short-term exposure - systemic effects is not required.
Acute/short-term and long-term exposure - local effects
Based on the available toxicological information, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate is not subject to classification for skin, eye and/or respiratory irritation and no worker DNEL for local effects following acute/short-term or long-term exposure is derived. In addition no skin sensitizing properties were observed.
This is in line with the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-repsonse for human health".
Long-term exposure - systemic effects
For the dermal route, the NO(A)EL of 1000 mg/kg bw/day from the key subacute oral toxicity study (BASF, 2006) is considered to represent the appropriate dose descriptor for systemic effects related to long-term dermal exposure to 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate.
In a 28 -day repeated dose toxicity study with 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate no substance-related adverse findings were obtained. Therefore, the no-observed-adverse-effect level (NOAEL) was 1000 mg/kg body weight per day in both sexes. A worst case dermal absorption of 100 % was assumed.
For the inhalation route, the NO(A)EL of 1000 mg/kg bw/day from the same subacute oral toxicity study (BASF, 2006) is considered to represent the appropriate dose descriptor for systemic effects related to long-term dermal inhalation to 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate. A DNEL was derived even though significant exposure via inhalation except to aerosols is highly unlikely due to very low vapour pressure of <0.000001 hPa at 20 °C. This is why a factor of only 1 was assumed for route to route (oral to inhalation) extrapolation.
In order to derive a worker DNEL and under the assumption of a daily exposure period of 8 hours, the oral NO(A)EL is converted into an inhalation NO(A)EC according to the following formula:
inhalation NO(A)EC = oral NO(A)EL × 1/sRV(rat) × ABSoral(rat)/ABSinhalation(human) × sRV(human)/wRV(human)
with:
oral NO(A)EL: 1000 mg/kg bw/day
sRV(rat): 0.38 m³/kg bw (8 hours) [standard respiratory volume of the rat]
ABSoral(rat)/ABSinhalation(human): 1 [ratio of oral absorption in the rat to inhalative absorption in the human]
sRV(human)/wRV(human): 6.7 m³/10 m³ [ratio of human standard respiratory volume to worker respiratory volume]
Accordingly, the oral NO(A)EL of 1000 mg/kg bw/day is transformed in an inhalation NO(A)EC of 1763 mg/m³.
The following assessment factors are used for the derivation of worker DNELs for dermal or inhalation exposure to 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate:
Interspecies factor (rat to human): 4 [used for the dermal route only]
Intraspecies factor (worker): 3
Exposure duration factor: 6 (subacute to chronic) [for the dermal and inhalation route]
Quality of whole database factor: 1
The resulting worker DNELs are:
worker DNEL (dermal exposure) = 1000 mg/kg bw/day / (4 × 3 × 6 × 1 × 1) = 1000 mg/kg bw/day /72 = 13.9 mg/kg bw/day
worker DNEL (inhalation exposure) = 1763 mg/m³ / (3 × 6 × 1 × 1) = 1763 mg/m³ / 18 = 97.9 mg/m³
This is in line with ECETOC technical report no. 110, 2010 "Guidance on assessment factors to derive a DNEL". and ECETOC technical report no. 86, 2003 “Derivation of assessment factors for human health risk assessment”.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 29 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 30
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.3 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.3 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard for the eyes
Additional information - General Population
Acute/short-term exposure - systemic effects
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified.
Referring to the available data on acute toxicity, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate displays no acute toxicity up to 5000 mg/kg bw determined in rats for the oral and dermal route. No experimental data for the inhalation route are available. Therefore, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate is not subject to classification for acute toxicity according to Directive 67/548/EEC and Regulation No 1272/2008, and consequently the derivation of worker DNELs for acute/short-term exposure - systemic effects is not required.
Acute/short-term and long-term exposure - local effects
Based on the available toxicological information, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate is not subject to classification for skin, eye and/or respiratory irritation and no general population DNEL for local effects following acute/short-term or long-term exposure is derived. In addition no skin sensitizing properties were observed.
This is in line with the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-repsonse for human health".
Long-term exposure - systemic effects
For the dermal route, the NO(A)EL of 1000 mg/kg bw/day from the key subacute oral toxicity study (BASF, 2006) is considered to represent the appropriate dose descriptor for systemic effects related to long-term dermal exposure to 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate.
In a 28 -day repeated dose toxicity study with 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate no substance-related adverse findings were obtained. Therefore, the no-observed-adverse-effect level (NOAEL) was 1000 mg/kg body weight per day in both sexes. A worst case dermal absorption of 100 % was assumed.
For the inhalation route, the NO(A)EL of 1000 mg/kg bw/day from the same subacute oral toxicity study (BASF, 2006) is considered to represent the appropriate dose descriptor for systemic effects related to long-term dermal inhalation to 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate. A DNEL was derived even though significant exposure via inhalation except to aerosols is highly unlikely due to very low vapour pressure of <0.000001 hPa at 20 °C. This is why a factor of only 1 was assumed for route to route (oral to inhalation) extrapolation.
In order to derive a worker DNEL and under the assumption of a daily exposure period of 8 hours, the oral NO(A)EL is converted into an inhalation NO(A)EC according to the following formula:
inhalation NO(A)EC = oral NO(A)EL × 1/sRV(rat) × ABSoral(rat)/ABSinhalation(human)
with:
oral NO(A)EL: 1000 mg/kg bw/day
sRV(rat): 1.15 m³/kg bw/day [standard respiratory volume of the rat]
ABSoral(rat)/ABSinhalation(human): 1 [ratio of oral absorption in the rat to inhalative absorption in the human]
Accordingly, the oral NO(A)EL of 1000 mg/kg bw/day is transformed in an inhalation NO(A)EC of 869.56 mg/m³.
For the oral route, the NO(A)EL of 1000 mg/kg bw/day from the same subacute oral toxicity study (BASF, 2006) is considered to represent the appropriate dose descriptor for systemic effects related to long-term exposure to 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate.
The following assessment factors are used for the derivation of general population DNELs for dermal, inhalation or oral exposure to 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate:
Interspecies factor (rat to human): 4 [used for the dermal and oral route only]
Intraspecies factor (general population): 5
Exposure duration factor: 6 (subacute to chronic) [for the dermal, inhalation and oral route]
Quality of whole database factor: 1
The resulting general population DNELs are:
general population DNEL (dermal exposure) = 1000 mg/kg bw/day / (4 × 5 × 6 × 1 × 1) = 1000 mg/kg bw/day / 120 = 8.3 mg/kg bw/day
general population DNEL (inhalation exposure) = 869.56 mg/m³ / (5 × 6 × 1 × 1) = 869.56 mg/m³ / 30 = 29 mg/m³
general population DNEL (oral exposure) = 1000 mg/kg bw/day / (4 × 5 × 6 × 1 × 1) = 1000 mg/kg bw/day / 120 = 8.3 mg/kg bw/day
This is in line withECETOC technical report no. 110, 2010 "Guidance on assessment factors to derive a DNEL". and ECETOC technical report no. 86, 2003 “Derivation of assessment factors for human health risk assessment”.
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