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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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”.