Quaternary ammonium compounds, C12-14-alkylethyldimethyl, Et sulfates

Toxicological Summary

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

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 a.i./kg bw/day from a 90-day repeated dose dietary toxicity study conducted with C12-18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation as follows: [NOAELoral rat ÷ SRvrat x (SRvhuman ÷ WSRvhuman) x (ABSoral-rat/ABSinh-human)] in accordance with REACH guidance document Chapter R.8, November (2012) where: NOAELoral rat = 113 mg a.i./kg bw/day; 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

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 a.i./kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with C12-18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation as follows: [NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document Chapter R.8, November (2012) where: NOAELoral rat = 113 mg a.i./kg bw/day; 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)

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

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 C12-18 TMAC. This dose descriptor, which is the starting point was corrected for route-to-route extrapolation as follows: [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

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 a.i./kg bw/day derived from a 90-day repeated dose dietary toxicity study conducted with C12-C18 TMAC. This dose descriptor which is the starting point was corrected for route-to-route extrapolation as follows: [NOAELoral rat x (ABSoral-rat/ABSderm-human)] in accordance with REACH guidance document Chapter R.8, November (2012) where: NOAELoral rat = 113 mg a.i./kg bw/day ; 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

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)