Reaction mass of 2-{[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and 2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-[2-(benzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-benzyl-2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-benzyl-N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride.

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

49.4 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

1 234.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

No data are available for the inhalation route. However, reliable repeated dose data via the oral route are available.

The calculation of the DNEL is based on an oral NOAEL observed in a subchronic repeated dose oral toxicity study with the registered substance (OECD 408; 2017).

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= NOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h) * (exposure duration rat/exposure duration worker)

= 1000 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (1/2) * 0.67 m³ * 7d/5d = 1234.2 mg/m³

As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of of inhalation absorption.

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)

Thus, the corrected starting point for workers was 1234.2 mg/m³ for inhalation.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

2

Justification:

based on a subchronic study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

for workers

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high-quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 400 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No data are available for the dermal route. However, reliable repeated dose data via the oral route are available.

The calculation of the DNEL is based on an oral NOAEL observed in a subchronic repeated dose oral toxicity study with the registered substance (OECD 408; 2017).

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) * (exposure duration rat/exposure duration worker)

= 1000 mg/kg bw/day *(1/1) * (7d/5d) = 1400 mg/kg bw/day.

It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

2

Justification:

based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

default

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

for workers

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high-quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

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:

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)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.7 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

434.8 mg/m³

Explanation for the modification of the dose descriptor starting point:

No data are available for the inhalation route. However, reliable repeated dose data via the oral route are available.

The calculation of the DNEL is based on an oral NOAEL observed from a subchronic repeated dose oral study with the (OECD 408) in rats.

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for general population:

= NOAELoral * (1/1.15 m³/kg bw/day (24h)) * (ABSoral-rat / ABSinh-human)

= 1000 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (1/2) = 434.8 mg/m³

As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of of inhalation absorption.

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)

Thus, the corrected starting point for general population was 434.8 mg/m³ for inhalation.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

2

Justification:

based on a subchronic study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

for general population

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high-quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No data are available for the dermal route. However, reliable repeated dose data via the oral route are available.

The calculation of the DNEL is based on an oral NOAEL observed from a subchronic repeated dose oral study with the (OECD 408) in rats.

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) = 1000 mg/kg bw/day *(1/1) = 1000 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

2

Justification:

based on a subschronic study

AF for interspecies differences (allometric scaling):

2.5

Justification:

default

AF for other interspecies differences:

4

Justification:

default

AF for intraspecies differences:

10

Justification:

for general population

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high-quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

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:

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)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

As the most reliable source of information, a subchronic repeated dose oral toxicity study performed with rats (OECD 408) was used to derive the DNEL (oral). The basis for the DNEL is the NOAEL= 1000 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

2

Justification:

based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

default

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

for general population

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high-quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)