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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.32 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:
19.92 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 rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the read-across substance C12-C18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat ÷ SRvrat x (SRvhuman ÷ WSRvhuman) x (ABSoral-rat/ABSinh-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012) ; where: NOAELoral rat = 113 mg/kg bw/d; SRvrat = 0.38 m3/kg bw; SRvhuman = 6.7 m3; WSRvhuman = 10 m3; ; ABSoral-rat = 10%; ABSinh-human = 100%.
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 (rat-to-human) since this is already accounted for when obtaining the corrected NOEC
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:
3 (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:
4.7 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):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
113 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 oral rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the read-across substance C12-C18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012) ; where: NOAELoral rat = 113 mg/kg bw/d; ABSoral-rat = 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):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-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:
0.98 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:
9.83 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 rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the read-across substance C12-C18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat ÷ SRvrat x (ABSoral-rat/ABSinh-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012) ; where: NOAELoral rat = 113 mg/kg bw/d; SRvrat = 1.15 m3/kg bw; ABSoral-rat = 10%; ABSinh-human = 100%.
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 (rat-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:
2.83 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):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
113 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 oral rat NOAEL of 113 mg/kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with the read-across susbtance C12-C18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’) November (2012) ; where: NOAELoral rat = 113 mg/kg bw/d; ABSoral-rat = 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):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-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:
2.83 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):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
113 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):
4
Justification:
Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-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

The data for the assessing the human health effects ofC16-C18 TMAC is based on the followingalkyltrimethylquaternary ammonium compounds (TMACs) with differing alkyl chain lengths and benzyl alkyldimethyl quarternary ammonium compound (ADBAC).

 

Alkyltrimethylquaternary ammonium compounds (TMACs) used for read-across:

  • quaternary ammonium compounds, coco alkyltrimethyl chlorides (R=C12-C18)
  • quaternary ammonium compounds, cetrimonium chloride (R= C16)
  • quaternary ammonium compounds, tallow alkyl trimethyl ammonium chloride (R=C16-C18 and C18 and unsaturated)
  • quaternary ammonium compounds, octadecyl trimethyl ammonium chloride (R=C18)

 

Benzyl alkyldimethyl quaternary ammonium compounds (ADBACs) used for read-across:

·        quaternary ammonium compounds, benzyl-C12-C16-alkyldimethyl, chloride (R=C12-C16)

 

The read-across is justified based on the TMACs and ADBAC core chemical structures. They are characterized by a positively charged ammonium group. In the case of TMACs, the nitrogen is bound to three methyl groups and the longer alkyl chain and in the ADBAC, one methyl group is replaced with abenzyl substituent. The positively charged quaternary ammonium group is balanced by a negatively charged chloride anion.

 

From a toxicology perspective, it is the positive entity (quaternized nitrogen) that is of relevance, with no influence from the benzyl substituent.The anionic part (chloride ion) does not contribute significantly to the toxicity of the substance. The primary toxic effect of these quaternary ammonium compounds involves disruption of the cytoplasmic membrane causing cell damage or lysis of the cell contents. Speed of uptake, distribution and metabolism are likely to be largely dependent on the actual alkyl chain length but the mechanism for the processes involved are the same whether it is C12 or C18, as demonstrated in this Chemical Safety Report.