Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.6 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
264 mg/m³
Explanation for the modification of the dose descriptor starting point:

No repeated dose inhalation toxicity study is available. Therefore, the DNEL is derived on basis of a subchronic repeated oral toxicity study in the rat. This oral NOAEL for rats was converted to the corresponding air concentration using a standard breathing volume for the rat of 0.38 m3/kg (for 8 hours exposure of workers). The resulting air concentration was additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m3 for base level, 10 m3 for light activity). A correction factor for difference between human (5 work days) and experimental exposure conditions (also 5 days) was not included (see "Additional information").

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor. The tested source substance is a structural analogue to the target substance with similar physico-chemical properties.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
6 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No repeated dose dermal toxicity study is available. Therefore, the DNEL is derived on basis of a subchronic repeated oral toxicity study in the rat (see "Additional information").

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (endpoint).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor. The tested source substance is a structural analogue to the target substance with similar physico-chemical properties.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

1.    Inhalation

Long term, systemic DNEL – exposure via inhalation (workers)

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived. This worker long-term DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

No studies have been undertaken by the inhalatory route to characterize the dose-response relationship for systemic effects. Therefore, it will be necessary to obtain a long-term inhalatory DNEL by route-to route extrapolation. Human data are not available.

Step 1:PoD and most sensitive endpoint: repeated dose toxicity (oral)

The NOAEL derived from an OECD TG 408 study performed with the partially unsaturated TEA-Esterquat was used as the PoD since no repeated dose inhalation study with the target substance is available. From the OECD TG 408 study the NOEL was determined to be 300 mg/kg bw/day. However, the interpretation of the sub-chronic study is somewhat hampered due to the detection of a bacterial infection in all dose groups. An overlying substance related systemic effect cannot be entirely excluded and thereforethe systemic NOEL of 300 mg/kg bw/day has to be used for risk assessmentpurposes (= used as NOAEL). But apart from this, there is no evidence for a potential serious health risk for humans.

Step 2:Modification into a correct starting point:  

Relevant dose descriptor (NOAEL): 300 mg/kg bw/day

Oral absorption of the rat / inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50/100

A 50 % oral absorption is assumed for TEA based Esterquats from in vivo toxicokinetic studies and used for the purpose of route-to-route extrapolation. As a worst-case assumption 100 % absorption after inhalatory exposure is assumed in absence of any experimental data as recommended in TGD R8.

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Correction for difference between human and experimental exposure conditions: 5 d rat/5 d worker

Corrected NOAEC (inhalation) for workers:

= 300 mg/kg bw/day× 0.5 × (1 / 0.38 m³/kg bw/day) × (6.7 m³/10 m³) × 1

= 264 mg/m³

Step 3: Overall AF= 25

Interspecies: According to Table R.8.4 in chapter R.8 of the ECHA Guidance Document no AF is needed when route (oral)-to route (inhalation) is applied.

Interspecies AF, remaining differences: no evidence for species differences in the general mode of

Action

Intraspecies AF (worker): 5

Interspecies AF, remaining differences: 2.5

Dose response relationship AF: 1

Exposure duration AF (subchronic to chronic): 2

Whole database AF: 1

The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor. The tested source substance is a structural analogue to the target substance with similar physico-chemical properties.

The effects seen in the 90-day study are only minor toxicological effects. The possibly substance related effects in the urinary bladder seen in the 90-day study have not been confirmed by the 28-day study. In the 28 day study there were no effects up to the limit dose. It is therefore not necessary to apply a factor to take account of this. The key studies were conducted according to regulatory standards and were adequately reported. The bacterial infection of the animals did not crucially influence the outcome of the study. Furthermore in the 28-day study no systemic effects have been detected up to the limit dose. The probable substance related effects in the urinary bladder seen in the 90-day study have thus not been confirmed by the 28-day study. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

 

In conclusion,long term systemic inhalation DNEL, workers = 10.6 mg/m3

Acute, systemic DNEL- exposure via inhalation (workers)

No acute inhalation toxicity study is available. The test substance has a low vapor pressure, so the potential for the unintended generation of inhalable forms such as dust or aerosols is low. The most likely route of human exposure for workers and consumers is the dermal route. However, small quantities of the TEA-Esterquats are manufactured into spray (product) applications for professional and consumer uses. For spray applications, the concentration of diluted preparations for use is ≤ 0.5% active ingredient (worst case). Results of laboratory animal studies show a very low acute toxicity after oral or dermal exposure. Therefore the acute intrinsic toxic activity of the TEA-Esterquats is considered to be very low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely.

Long term & acute, local DNEL- exposure via inhalation (workers)

A DNEL acute - local effect is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008.

2.    Dermal

No studies have been undertaken by the dermal route to characterize the dose-response relationship for systemic effects therefore it will be necessary to obtain a long-term dermal DNEL by route-to-route extrapolation. In the worst case (under occlusive conditions) only up to 2% absorption occurred after dermal application (data taken from HERA RAR 2009).

 

Long term, systemic DNEL- exposure via dermal route (workers)

Step 1:PoD and most sensitive endpoint: repeated dose toxicity (oral)

The NOAEL derived from an OECD TG 408 study performed with the partially unsaturated TEA-Esterquat was used as the PoD since no repeated dose dermal study with the target substance is available. From the OECD TG 408 study the NOEL was determined to be 300 mg/kg bw/day. However, the interpretation of the sub-chronic study is somewhat hampered due to the detection of a bacterial infection in all dose groups. An overlying substance related systemic effect cannot be entirely excluded and thereforethe systemic NOEL of 300 mg/kg bw/day has to be used for risk assessmentpurposes (= used as NOAEL). But apart from this, there is no evidence for a potential serious health risk for humans.

Step 2:Modification into a correct starting point:

Relevant dose descriptor (NOAEL): 300 mg/kg bw/day

In ECHA guidance R.8 it is stated that “the default situation, in the absence of information, is to assume the same bioavailability for experimental animals and humans for a particular exposure route.” Therefore, in the present situation, as no information is available for the dermal absorption in humans, experimental data from dermal toxicokinetic studies was used showing only 2% absorption in pig and rat skin.

Corrected NOAEL (dermal) for workers:

= 300 mg/kg bw/day× 2

= 600 mg/kg bw/day

Step 3: Overall AF= 100

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Interspecies AF, remaining differences: Interspecies differences are fully covered by the allometric

scaling

Intraspecies AF (worker): 5

Dose-response relationship AF: 1

Exposure duration AF (subchromic to chronic): 2

Effects on urinary bladder such as enhanced desquamation and regressive epithelial changes are probable substance related effects in the 90-day study, which have not been confirmed by the 28-day study. Therefore an additional AF for dose response and endpoint specific severity was not considered necessary. The key studies were conducted to regulatory standards and were adequately reported. The bacterial infection of the animals did not influence the outcome of the study. Furthermore in the 28-day study no systemic effects have been detected up to the limit dose. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

 

In conclusion,long term systemic dermal DNEL, workers = 6 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (workers)

According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, „a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute dermal toxicity with the LD50 of >2000 mg/kg. Therefore, the DNEL is not required.

Long term & acute, local DNEL- dermal exposure (workers)

A DNEL long term/acute - local effects is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008.

Hazard to the eye-local effects (worker)

The substance is not classified for eye irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

 

 

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:

Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
79 mg/m³
Explanation for the modification of the dose descriptor starting point:

No repeated dose inhalation toxicity study is available. The DNEL is derived on basis of a subchronic repeated dose oral toxicity study. This oral NOAEL for rats was converted to the corresponding air concentration using a standard breathing volume for the rat of 1.35 m3/kg for 24 hours exposure (see "Additional Information").

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor. The tested source substance is a structural analogue to the target substance with similar physico-chemical properties.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
2.3 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
450 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No repeated dose dermal toxicity study is available. Therefore, the DNEL is derived on basis of a subchronic repeated oral toxicity study in the rat (see "Additional information").

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (endpoint).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor. The tested source substance is a structural analogue to the target substance with similar physico-chemical properties.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor. The tested source substance is a structural analogue to the target substance with similar physico-chemical properties.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

1.    Inhalation

Long term, systemic DNEL – exposure by inhalation (general population)

Using a conservative approach, a DNEL (long-term inhalation exposure) is derived. This long-term DNEL for the general population is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

Step 1:PoD and most sensitive endpoint: repeated dose toxicity (oral)

The NOAEL derived from an OECD TG 408 study performed with the partially unsaturated TEA-Esterquat was used as the PoD since no repeated dose inhalation study with the target substance is available. From the OECD TG 408 study the NOEL was determined to be 300 mg/kg bw/day. However, the interpretation of the sub-chronic study is somewhat hampered due to the detection of a bacterial infection in all dose groups. An overlying substance related systemic effect cannot be entirely excluded and therefore the systemic NOEL of 300 mg/kg bw/day has to be used for risk assessmentpurposes (= used as NOAEL). But apart from this, there is no evidence for a potential serious health risk for humans.

Step 2:Modification into a correct starting point:  

Relevant dose descriptor (NOAEL): 300 mg/kg bw/day

Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.35 m³/kg bw

Oral absorption of the rat / inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50/100

A 50 % oral absorption is assumed for TEA based Esterquats from in vivo toxicokinetic studies and used for the purpose of route-to-route extrapolation. As a worst-case assumption 100 % absorption after inhalatory exposure is assumed in absence of any experimental data as recommended in TGD R8

Differences experimental/human exposure conditions: 5d/24h rat vs.7d/24h (general population)

Corrected NOAEC (inhalation) for general population:

= 300 mg/kg bw/day× 0.5 × (1 / 1.35 m³/kg bw)×0.71

= 79 mg/m³

Step 3:Overall AF= 50

Interspecies: According to Table R.8.4 in chapter R.8 of the ECHA Guidance Document no AF is needed when route (oral)-to route (inhalation) is applied.

Interspecies AF, remaining differences: no evidence for species differences in the general mode of

Action

Intraspecies AF (general population): 10

Interspecies AF, remaining differences: 2.5

Dose response relationship AF: 1

Exposure duration AF (subchronic to chronic): 2

In conclusion,long term systemic inhalation DNEL, general population= 1.6 mg/m3

Acute, systemic DNEL- exposure via inhalation (general population)

No acute inhalation toxicity study is available. The test substance has a low vapor pressure, so the potential for the unintended generation of inhalable forms such as dust or aerosols is low. The most likely route of human exposure for workers and consumers is the dermal route. However, small quantities of the TEA-Esterquats are manufactured into spray (product) applications for professional and consumer uses. For spray applications, the concentration of diluted preparations for use is ≤ 0.5% active ingredient (worst case). Results of laboratory animal studies show a very low acute toxicity after oral or dermal exposure. Therefore the acute intrinsic toxic activity of the TEA-Esterquats is considered to be very low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely.

Long term & acute, local DNEL- exposure via inhalation (general population)

A DNEL acute/long term - local effect is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008.

2.    Dermal

Long term, systemic DNEL- exposure via dermal route (general population)

Step 1:PoD and most sensitive endpoint: repeated dose toxicity (oral)

The NOAEL derived from an OECD TG 408 study performed with the partially unsaturated TEA-Esterquat was used as the PoD since no repeated dose dermal study with the target substance is available. From the OECD TG 408 study the NOEL was determined to be 300 mg/kg bw/day. However, the interpretation of the sub-chronic study is somewhat hampered due to the detection of a bacterial infection in all dose groups. An overlying substance related systemic effect cannot be entirely excluded and thereforethe systemic NOEL of 300 mg/kg bw/day has to be used for risk assessmentpurposes (=used as NOAEL). But apart from this, there is no evidence for a potential serious health risk for humans.

Step 2:Modification into a correct starting point:

Relevant dose descriptor (NOAEL): 300 mg/kg bw/day

In ECHA guidance R.8 it is stated that “the default situation, in the absence of information, is to assume the same bioavailability for experimental animals and humans for a particular exposure route.” Therefore, in the present situation, as no information is available for the dermal absorption in humans, experimental data from dermal toxicokinetic studies was used showing only 2% absorption in pig and rat skin.

Correction for difference between human and experimental exposure conditions: 5d animal/7d general population

Corrected NOAEL (dermal) for general population:

= 300 mg/kg bw/day× 2 x 0.75

= 450 mg/kg bw/day

Step 3:Overall AF= 200

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Interspecies AF, remaining differences: Interspecies differences are fully covered by the allometric

scaling

Intraspecies AF (general population): 10

Dose-response relationship AF: 1

Exposure duration AF (subchronic to chronic): 2

In conclusion,long term systemic dermal DNEL, general population = 2.3 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (general population)

According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, „a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute dermal toxicity with the LD50 of >2000 mg/kg. Therefore, the DNEL is not required.

Long term & acute, local DNEL- dermal exposure (general population)

A DNEL acute - local effects is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation EC No 1272/2008.

Long term, systemic DNEL – exposure by oral route (general population)

Step 1: PoD and most sensitive endpoint: repeated dose toxicity (oral)

The NOAEL derived from an OECD TG 408 study performed with the partially unsaturated TEA-Esterquat was used as the PoD. From the OECD TG 408 study the NOEL was determined to be 300 mg/kg bw/day. However, the interpretation of the sub-chronic study is somewhat hampered due to the detection of a bacterial infection in all dose groups. An overlying substance related systemic effect cannot be entirely excluded and thereforethe systemic NOEL of 300 mg/kg bw/day has to be used for risk assessmentpurposes (=used as NOAEL). But apart from this, there is no evidence for a potential serious health risk for humans.

Step 2:Relevant dose descriptor (NOAEL): 300 mg/kg bw/day

Step 3:Overall AF= 200

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Interspecies AF, remaining differences: Interspecies differences are fully covered by the allometric

scaling

Intraspecies AF (general population): 10

Dose-response relationship AF: 1

Exposure duration AF (subchronic to chronic): 2

In conclusion,long term systemic oral DNEL, general population= 1.5 mg/kg bw/day

Acute, systemic DNEL- exposure by oral route (general population)

According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, "a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute dermal toxicity with the LD50 >5000 mg/kg bw. Therefore, a DNEL is not required.

Hazard to the eye-local effects (general population)

The substance is not classified for eye irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:

Characterization of dose [concentration]-response for human health. Version 2.1, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterization, Version 3.0, May 2016