Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.96 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
DNEL value:
23.75 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant dose descriptor selected to derive the inhalation DNEL, was the oral dog NOAEL of 47.5 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study

conducted with benzyl C12-16 alkyl dimethyl ammonium chloride. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral dog ÷ SRvdog x (SRvhuman ÷ WSRvhuman) x (ABSoral-dog/ABSinh-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral dog = 47.5 mg/kg bw/day; ABSoral-dog = 10%; ABSinh-human = 100%; SRvdog = 0.1 m3/kg bw; SRvhuman = 5 m3; WSRvhuman = 10 m3. The respiratory volume for dog was calculated using the allometric equation (Inhalation rate (m3/day) = 0.67*W^0.7091; where W = body weight in kg; W = 18 kg as per REACH guidance document R.8) mentioned in the US EPA recommended biological values document [US EPA (1988). Recommendations for and documentation of biological values for use in risk assessment. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/6-87/008 (NTIS PB88179874)].

AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
1
Justification:
Although the basis for the NOAEL is data from a 90-day study as this represented the lowest NOAEL. However, there are long-term chronic studies available that do not show lower NOAEL, indicating that NOAEL is not related to duration of the study.
AF for interspecies differences (allometric scaling):
1
Justification:
ECETOC proposed in 2010, based on the scientific evidence, that remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used. However, additionally it can be remarked all available data do not really indicate systemic effects, but to consequences following local irritation. For the oral studies the effects are mainly on the gastro-intestinal system. Especially between species there are considerable anatomical differences in stomach and further GI system which could be a cause for larger variation in response between. To accommodate for this the ECETOC value of 1 is changed to 2.
AF for other interspecies differences:
2
Justification:
Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
AF for intraspecies differences:
3
Justification:
Intraspecies variation (workers). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
8.4
Modified dose descriptor starting point:
NOAEL
DNEL value:
47.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The relevant dose descriptor selected to derive the dermal DNEL, was the sub-chronic oral dog NOAEL of 47.5 mg/kg bw/day based on absence of treatment-related effects at the tested doses of benzyl C12-16 alkyl dimethyl ammonium chloride. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral dog x (ABSoral-dog/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral dog = 47.5 mg/kg bw/day; ABSoral-dog = 10%; ABSderm-human = 10%).
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
1
Justification:
Although the basis for the NOAEL is data from a 90-day study as this represented the lowest NOAEL. However, there are long-term chronic studies available that do not show lower NOAEL, indicating that NOAEL is not related to duration of the study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (dog-to-human)
AF for other interspecies differences:
2
Justification:
ECETOC proposed in 2010, based on the scientific evidence, that remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used. However, additionally it can be remarked all available data do not really indicate systemic effects, but to consequences following local irritation. For the oral studies the effects are mainly on the gastro-intestinal system. Especially between species there are considerable anatomical differences in stomach and further GI system which could be a cause for larger variation in response between. To accommodate for this the ECETOC value of 1 is changed to 2.
AF for intraspecies differences:
3
Justification:
Intraspecies variation (workers). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.64 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
16.38 mg/m³
Explanation for the modification of the dose descriptor starting point:
The relevant dose descriptor selected to derive the inhalation DNEL, was the oral dog NOAEL of 47.5 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with benzyl C12-16 alkyl dimethyl ammonium chloride. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral dog ÷ SRvdog x (ABSoral-dog ÷ ABSinh-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral dog = 47.5 mg/kg bw/day; ABSoral-dog = 10%; ABSinh-human = 100%; SRvdog = 0.29 m3/kg bw. The respiratory volume for dog was calculated using the allometric equation (Inhalation rate (m3/day) = 0.67*W^0.7091; where W = body weight in kg; W = 18 kg as per REACH guidance document R.8) mentioned in the US EPA recommended biological values document [US EPA (1988). Recommendations for and documentation of biological values for use in risk assessment. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/6-87/008 (NTIS PB88179874)].
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
1
Justification:
Although the basis for the NOAEL is data from a 90-day study as this represented the lowest NOAEL. However, there are long-term chronic studies available that do not show lower NOAEL, indicating that NOAEL is not related to duration of the study.
AF for interspecies differences (allometric scaling):
1
Justification:
No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (dog-to-human) since this is already accounted for when obtaining the corrected NOEC
AF for other interspecies differences:
2
Justification:
ECETOC proposed in 2010, based on the scientific evidence, that remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used. However, additionally it can be remarked all available data do not really indicate systemic effects, but to consequences following local irritation. For the oral studies the effects are mainly on the gastro-intestinal system. Especially between species there are considerable anatomical differences in stomach and further GI system which could be a cause for larger variation in response between. To accommodate for this the ECETOC value of 1 is changed to 2.
AF for intraspecies differences:
5
Justification:
Intraspecies variation (general population). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
14
Modified dose descriptor starting point:
NOAEL
DNEL value:
47.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The relevant dose descriptor selected to derive the dermal DNEL, was the sub-chronic oral dog NOAEL of 47.5 mg/kg bw/day based on absence of treatment-related effects at the tested doses of benzyl C12-16 alkyl dimethyl ammonium chloride. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral dog x (ABSoral-dog/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral dog = 47.5 mg/kg bw/d; ABSoral-dog = 10%; ABSderm-human = 10%).
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
1
Justification:
Although the basis for the NOAEL is data from a 90-day study as this represented the lowest NOAEL. However, there are long-term chronic studies available that do not show lower NOAEL, indicating that NOAEL is not related to duration of the study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (dog-to-human)
AF for other interspecies differences:
2
Justification:
ECETOC proposed in 2010, based on the scientific evidence, that remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used. However, additionally it can be remarked all available data do not really indicate systemic effects, but to consequences following local irritation. For the oral studies the effects are mainly on the gastro-intestinal system. Especially between species there are considerable anatomical differences in stomach and further GI system which could be a cause for larger variation in response between. To accommodate for this the ECETOC value of 1 is changed to 2.
AF for intraspecies differences:
5
Justification:
Intraspecies variation (general population). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH and ECETOC guidance
Overall assessment factor (AF):
14
Modified dose descriptor starting point:
NOAEL
DNEL value:
47.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation needed.
AF for dose response relationship:
1
Justification:
Dose-response (starting point is a NOAEL)
AF for differences in duration of exposure:
1
Justification:
Although the basis for the NOAEL is data from a 90-day study as this represented the lowest NOAEL. However, there are long-term chronic studies available that do not show lower NOAEL, indicating that NOAEL is not related to duration of the study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (dog-to-human)
AF for other interspecies differences:
2
Justification:
ECETOC proposed in 2010, based on the scientific evidence, that remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used. However, additionally it can be remarked all available data do not really indicate systemic effects, but to consequences following local irritation. For the oral studies the effects are mainly on the gastro-intestinal system. Especially between species there are considerable anatomical differences in stomach and further GI system which could be a cause for larger variation in response between. To accommodate for this the ECETOC value of 1 is changed to 2.
AF for intraspecies differences:
5
Justification:
Intraspecies variation (general population). ECETOC proposed in 2010, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Good quality
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population