3-((C12-18)-acylamino)-N-(2-((2-hydroxyethyl)amino)-2-oxoethyl)-N,N-dimethyl-1-propanaminium chloride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.47 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other:

Overall assessment factor (AF):

75

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

185 mg/m³

Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

 

Modified dose desciptor starting point = Dose descriptor starting point x Correction for differences in respiratory volume x Correction for differences in bioavailability x correction for light activity at work x Correction for differences between humain and experimental exposure conditions

 

With

- Correction for differences in respiratory volume (SRV) = 1 / 0.38 = 2.63

- Correction for differences in bioavailability (ABS) = 0.5 

The correction factor for differences in bioavailability is calculated according to the rules described in the following table and using information provided in IUCLID endpoint summary of section 7.1 when available. Note that if no (or partial) information is provided in the endpoint summary of IUCLID section 7.1, the DNEL calculator uses default values as explained in ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8. In addition, in the event of using dermal-to-inhalation or dermal-to-oral extrapolation, if there is no information about dermal absorption the DNEL calculator will use a dermal absorption of 10% as a reasonable worst-case scenario.

- Correction factor for light activity at work (WORKER) = 6.7 / 10 = 0.67

There is a difference in respiratory volumes between humans at rest (standard human respiratory volume: 6.7 m3/kg bw/8h) and humans performing a light activity (worker respiratory volume for light activity: 10 m3/kg bw/8h). Therefore for the derivation of worker-DNEL for inhalation route a correction factor of 0.67 (result from the ratio of the values above) needs to be applied.

- Correction for differences between human and experimental exposure conditions (EXPCOND) = 1.4

This correction factor is used to account for differences in the exposure conditions of experimental animals in a test study that may differ from the ones of the worker (or the general population).

 

Modified dose desciptor starting point = 150 x 2.63 x 0.5 x 0.67 x 1.4 = 185 mg/m³

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

1

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

5

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

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:

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:

0.7 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other:

Overall assessment factor (AF):

300

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

210 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

 

Modified dose desciptor starting point = Dose descriptor starting point x Correction for differences in respiratory volume x Correction for differences in bioavailability x correction for light activity at work x Correction for differences between humain and experimental exposure conditions

 

With

- Correction for differences in respiratory volume (SRV) = 1 

- Correction for differences in bioavailability (ABS) = 1

The correction factor for differences in bioavailability is calculated according to the rules described in the following table and using information provided in IUCLID endpoint summary of section 7.1 when available. Note that if no (or partial) information is provided in the endpoint summary of IUCLID section 7.1, the DNEL calculator uses default values as explained in ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8. In addition, in the event of using dermal-to-inhalation or dermal-to-oral extrapolation, if there is no information about dermal absorption the DNEL calculator will use a dermal absorption of 10% as a reasonable worst-case scenario.

- Correction factor for light activity at work (WORKER) = 1

There is a difference in respiratory volumes between humans at rest (standard human respiratory volume: 6.7 m3/kg bw/8h) and humans performing a light activity (worker respiratory volume for light activity: 10 m3/kg bw/8h). Therefore for the derivation of worker-DNEL for inhalation route a correction factor of 0.67 (result from the ratio of the values above) needs to be applied.

- Correction for differences between human and experimental exposure conditions (EXPCOND) = 1.4

This correction factor is used to account for differences in the exposure conditions of experimental animals in a test study that may differ from the ones of the worker (or the general population).

 

Modified dose desciptor starting point = 150 x 1 x 1 x 1 x 1.4 = 210 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

5

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Even if the registered substance is classified Eye Damage 1, H318 and Skin Sensitization 1, H317, the potential risk to workers is controlled thanks to the risk management measures in place and mentionned in the Safety Data Sheet of Montaline C40.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.435 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other:

Overall assessment factor (AF):

150

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

65.3 mg/m³

Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

 

Modified dose desciptor starting point = Dose descriptor starting point x Correction for differences in respiratory volume x Correction for differences in bioavailability x Correction for differences between humain and experimental exposure conditions

 

With

- Correction for differences in respiratory volume (SRV) = 1 / 1.15 = 0.87

- Correction for differences in bioavailability (ABS) = 0.5 

The correction factor for differences in bioavailability is calculated according to the rules described in the following table and using information provided in IUCLID endpoint summary of section 7.1 when available. Note that if no (or partial) information is provided in the endpoint summary of IUCLID section 7.1, the DNEL calculator uses default values as explained in ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8. In addition, in the event of using dermal-to-inhalation or dermal-to-oral extrapolation, if there is no information about dermal absorption the DNEL calculator will use a dermal absorption of 10% as a reasonable worst-case scenario.

- Correction for differences between human and experimental exposure conditions (EXPCOND) = 1

This correction factor is used to account for differences in the exposure conditions of experimental animals in a test study that may differ from the ones of the worker (or the general population).

 

Modified dose desciptor starting point = 150 x 0.87 x 0.5 x 1 = 65.3 mg/m³

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

1

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

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:

0.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other:

Overall assessment factor (AF):

600

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

 

Modified dose desciptor starting point = Dose descriptor starting point x Correction for differences in respiratory volume x Correction for differences in bioavailability x Correction for differences between humain and experimental exposure conditions

 

With

- Correction for differences in respiratory volume (SRV) = 1 

- Correction for differences in bioavailability (ABS) = 1

The correction factor for differences in bioavailability is calculated according to the rules described in the following table and using information provided in IUCLID endpoint summary of section 7.1 when available. Note that if no (or partial) information is provided in the endpoint summary of IUCLID section 7.1, the DNEL calculator uses default values as explained in ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8. In addition, in the event of using dermal-to-inhalation or dermal-to-oral extrapolation, if there is no information about dermal absorption the DNEL calculator will use a dermal absorption of 10% as a reasonable worst-case scenario.

- Correction for differences between human and experimental exposure conditions (EXPCOND) = 1

This correction factor is used to account for differences in the exposure conditions of experimental animals in a test study that may differ from the ones of the worker (or the general population).

 

Modified dose desciptor starting point = 150 x 1 x 1 x 1 = 150 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other:

Overall assessment factor (AF):

600

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

 

Modified dose desciptor starting point = Dose descriptor starting point x Correction for differences in respiratory volume x Correction for differences in bioavailability x Correction for differences between humain and experimental exposure conditions

 

With

- Correction for differences in respiratory volume (SRV) = 1 

- Correction for differences in bioavailability (ABS) = 1

The correction factor for differences in bioavailability is calculated according to the rules described in the following table and using information provided in IUCLID endpoint summary of section 7.1 when available. Note that if no (or partial) information is provided in the endpoint summary of IUCLID section 7.1, the DNEL calculator uses default values as explained in ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8. In addition, in the event of using dermal-to-inhalation or dermal-to-oral extrapolation, if there is no information about dermal absorption the DNEL calculator will use a dermal absorption of 10% as a reasonable worst-case scenario.

- Correction for differences between human and experimental exposure conditions (EXPCOND) = 1

This correction factor is used to account for differences in the exposure conditions of experimental animals in a test study that may differ from the ones of the worker (or the general population).

 

Modified dose desciptor starting point = 150 x 1 x 1 x 1 = 150 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

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:

low hazard (no threshold derived)

Additional information - General Population

General population

No assessment and notably no DNEL is required for the general public, as the latter is only exposed to the substance via the use of final cosmetic products. Assessment of human health effects for such exposure is not required by REACH.

No DNELs are required for acute toxic effects, sensitization, irritation effects, long-term DNELs are sufficient to cover systemic effects, as a worst-case. Furthermore most of these DNELs can not be calculated with the available qualitative or single-dose data.

For the long-term exposure, the dermal DNEL and inhalation DNEL are extrapolated from oral route according to the NOAEL = 150 mg/kg bw/day obtained from a rat 28days study.