Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
155 mg/m³
Explanation for the modification of the dose descriptor starting point:
No justification for route to route extrapolation needed
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on oral 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No justification for route to route extrapolation needed
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on oral 90-day study
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Acute systemic effects

Oral: According to the Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Consumer products contain a maximum of 15 % amine oxide and are not classified. In addition, high peak exposure is unlikely to occur.

Dermal:In an acute dermal toxicity study there were no mortalities, signs of systemic toxicity or abnormalities observed during necropsy which would lead to classification. It can therefore be expected that acute dermal exposure of the substance causes no systemic toxic effects and hence no DNEL has to be derived.

Inhalation: No acute inhalation study is available. The substance has a very low estimated vapour pressure and therefore peak exposures via this route are not anticipated. The long term inhalation DNEL will be protective of short term exposures

 

Acute local effects

Dermal: The substance is classified as a skin irritant and is considered to have a low hazard potential.

Eyes: The substance is classified as corrosive to eyes and is considered to have a medium hazard potential.

Inhalation: No data on local effects resulting from acute inhalation exposure are available. It is not anticipated that exposure via the inhalation route is likely to occur at levels that may cause local effects.

 

Long-term systemic effects

Dermal: No systemic effects were observed in any of the repeated dose dermal toxicity studies available. In order to derive the DNEL route to route extrapolation is used from the oral NOAEL of 88 mg/kg bw/day. This study provides the highest NOAEL below the lowest LOAEL. The oral NOAEL is modified to take account of the human dermal penetration (8 %) by dividing by a factor of 0.08 resulting in a NOAEL after route to route extrapolation of 1100 mg/kg bw/day. Assessment factors applied to this NOAEL are based on the recommendations in the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.8: Characterisation of dose [concentration]-response for human healthcare as follows: AF(total) = 2 (subchronic to chronic) x 2.5 (interspecies) x 4 (allometric scaling) x 5 (intraspecies, workers) = 100.

Systemic long-term dermal DNEL (worker) = 11 mg/kg bw/day

 

Inhalation: No repeat dose inhalation studies are available. In order to derive the DNEL route to route extrapolation is used from the oral NOAEL of 88 mg/kg bw/day. This study provides the highest NOAEL below the lowest LOAEL. The NOAEL(oral) was converted into a NOAEC(inhalation) using the equation described in Figure R. 8-3 of the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.8: Characterisation of dose [concentration]-response for human healthcare. Absorption via the oral route for rat is 100 % and via the inhalation route for humans is assumed to be 100 % as worse case. Using this method resulted in a NOAEC of 155.2 mg/m3. Assessment factors are applied to the NOAEC based on the recommendations in the above Guidance document as follows: AF(total) = 2 (subchronic to chronic) x 2.5 (other interspecies differences) x 5 (intraspecies, workers) = 25.

Systemic long-term inhalation DNEL (worker) = 6.2 mg/m3

 

Long term local effects

Dermal:A subchronic (90-d) dermal toxicity study in mice with focus on local tolerability was performed using C12-14 AO. The LOEL for local effects from this study was 0.27 % AO w/v. However, the relevance of these studies to humans is doubtful. The available human data (from HRIPT studies) show that a concentration of 0.75% AO is well-tolerated (mild to moderate erythema) under severe conditions (24-h exposure, occluded, 9 exposures over 3 weeks). The HRIPT studies are not themselves suitable for use in deriving a DNEL and hence a qualitative assessment will be performed.

Inhalation: No data on local effects resulting from long term inhalation exposure are available. It is not anticipated that exposure via the inhalation route is likely to occur at levels that may cause local effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.53 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
76.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
No justification for route to route extrapolation needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on oral 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No justification for route to route extrapolation needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on oral 90-day study
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.44 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
88 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation is not used
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
DNEL is based on oral 90-day study
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Acute systemic effects

Oral: According to the Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Consumer products contain a maximum of 15 % amine oxide and are not classified. In addition, high peak exposure is unlikely to occur.

Dermal:In an acute dermal toxicity study there were no mortalities, signs of systemic toxicity or abnormalities observed during necropsy which would lead to classification. It can therefore be expected that acute dermal exposure of the substance causes no systemic toxic effects and hence no DNEL has to be derived.

Inhalation: No acute inhalation study is available. The substance has a very low estimated vapour pressure and therefore peak exposures via this route are not anticipated. The long term inhalation DNEL will be protective of short term exposures

 

Acute local effects

Dermal:The substance is classified as a skin irritant and is considered to have a low hazard potential.

Eyes: The substance is classified as corrosive to eyes and is considered to have a medium hazard potential.

Inhalation:No data on local effects resulting from acute inhalation exposure are available. It is not anticipated that exposure via the inhalation route is likely to occur at levels that may cause local effects.

 

Long-term systemic effects

Oral:The NOAEL of 88 mg AO/kg bw/day for repeated dose oral toxicity used to calculate the DNEL is derived from a 90-day feeding study in rats. This study provides the highest NOAEL below the lowest LOAEL. Assessment factors applied to this NOAEL are based on the recommendations in the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.8: Characterisation of dose [concentration]-response for human healthcare as follows: AF(total) = 2 (subchronic to chronic) x 2.5 (interspecies) x 4 (allometric scaling) x 10 (intraspecies, consumers) = 200

Systemic long-term oral DNEL (consumer) = 0.44 mg/kg bw/day

 

Dermal: No systemic effects were observed in any of the repeated dose dermal toxicity studies available. In order to derive the DNEL route to route extrapolation is used from the oral NOAEL of 88 mg/kg bw/day . This study provides the highest NOAEL below the lowest LOAEL. The oral NOAEL is modified to take account of the human dermal penetration (8 %) by dividing by a factor of 0.08 resulting in a NOAEL after route to route extrapolation of 1100 mg/kg bw/day. Assessment factors applied to this NOAEL are based on the recommendations in the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.8: Characterisation of dose [concentration]-response for human healthcare as follows: AF(total) = 2 (subchronic to chronic) x 2.5 (interspecies) x 4 (allometric scaling) x 10 (intraspecies, consumers) = 200.

Systemic long-term dermal DNEL (consumer) = 5.5 mg/kg bw/day

 

Inhalation: No repeat dose inhalation studies are available. In order to derive the DNEL route to route extrapolation is used from the oral NOAEL of 88 mg/kg bw/day. This study provides the highest NOAEL below the lowest LOAEL. The NOAEL(oral) was converted into a NOAEC(inhalation) using the equation described in Figure R. 8-3 of the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.8: Characterisation of dose [concentration]-response for human healthcare. Absorption via the oral route for rat is 100 % and via the inhalation route for humans is assumed to be 100 % as worse case. Using this method resulted in a NOAEC of 76.5 mg/m3. Assessment factors are applied to the NOAEC based on the recommendations in the above Guidance document as follows: AF(total) = 2 (subchronic to chronic) x 2.5 (other interspecies differences) x10 (intraspecies, consumers) = 50.

Systemic long-term inhalation DNEL (consumer) = 1.53 mg/m3

 

Long term local effects

Dermal: A subchronic (90-d) dermal toxicity study in mice with focus on local tolerability was performed using C12-14 AO. The LOEL for local effects from this study was 0.27 % AO w/v. However, the relevance of these studies to humans is doubtful. The available human data (from HRIPT studies) show that a concentration of 0.75% AO is well-tolerated (mild to moderate erythema) under severe conditions (24-h exposure, occluded, 9 exposures over 3 weeks). The HRIPT studies are not themselves suitable for use in deriving a DNEL and hence a qualitative assessment will be performed.

 

Inhalation: No data on local effects resulting from long term inhalation exposure are available. It is not anticipated that exposure via the inhalation route is likely to occur at levels that may cause local effects.