C16-18 (evennumbered, C18 unsaturated) alkyl bis(2-hydroxyethyl) amine oxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.48 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:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

37 mg/m³

Explanation for the modification of the dose descriptor starting point:

ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure; this has been included in this case due to a lack of data or the percentage of oral absorption. Therefore a factor of 2 was applied. Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/0.38 * 6.7/10 = mg/m3 inhalation NOAEC for workers. An additional adjust was made as recommended in ECHA guidance R8.4.3. The oral exposure for the rats was 7 days a week but inhalation exposure of workers is considered to be 5 days a week. This is adjusted by dividing the NOEC by 5/7 or 0.714286.DNELs

AF for dose response relationship:

1

Justification:

There was a clear dose response in the study.

AF for differences in duration of exposure:

2

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC.

AF for other interspecies differences:

2.5

Justification:

ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.

AF for intraspecies differences:

5

Justification:

ECHA guidance recommends a factor of 5 for intraspecies differences for workers.

AF for the quality of the whole database:

1

Justification:

While the DNEL is based on a read across substance, the read across substance is considered to be a worst case and will not be less toxic than Ethanol, 2,2’-iminobis-N-tallow alkyl derivatives, N-oxides. Therefore a factor of 1 was used.

AF for remaining uncertainties:

1

Justification:

All uncertainties are already included so a factor of 1 is applied.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.3 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):

100

Dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption. So the Oral NOAEL can be used also as the dermal repeat dose NOAEL as the basis for calculating Dermal DNELs.

AF for dose response relationship:

1

Justification:

There was a clear dose response in the study.

AF for differences in duration of exposure:

2

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA guidance recommends as factor of 4 for Allometric scaling from effects in the rat to humans, to compensate for the different metabolic rates.

AF for other interspecies differences:

2.5

Justification:

ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.

AF for intraspecies differences:

5

Justification:

ECHA guidance recommends a factor of 5 for intraspecies differences for workers.

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a NOAEL from a conservative read across substance believed to be a worst case for repeat dose toxicity, the study is fully GLP compliant.

AF for remaining uncertainties:

1

Justification:

All uncertainties are already included so a factor of 1 is applied.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Explanation for the modification of the dose descriptor starting point:

Ethanol, 2,2’-iminobis-N-tallow alkyl derivatives, N-oxides is not clasified as irritating to skin but is irritating to eyes.  Therefore long term local effects on the skin would be no more than mild irritation.  Based on the conditions of use and qualitative risk assessment it is considered not necessary to establish a DNEL for long term local effects from dermal exposure.

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

The information available for Ethanol, 2,2’-iminobis-N-tallow alkyl derivatives, N-oxides and the read across sources 2,2’-(octadec-9-enylimino)diethanol and Ethanol, 2.2’-iminobis,-N-tallow alkyl derivatives are consistent. Adverse effects were mainly seen at local effects in the gastrointestinal tract including irritation to the fore stomach and foamy macrophages. There were no apparent systemic adverse effects, these local effects leading to decreased bodyweight and bodyweight gain in the 150mg/kg bodyweight /day top dose groups assumed to be secondary to the local effects seen in the gastrointestinal tract. The consistency in the effects and the NOAEL values together with the similarities in structure, in particular in their carbon chain distribution are sufficient support for the read across used. Therefore the DNELs calculated based on the read across NOAEL will provide adequate protection for workers from any possibly systemic effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.22 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:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

11.11 mg/m³

Explanation for the modification of the dose descriptor starting point:

ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs (oral absorption assumed to default to 50% and inhalation to 100%). Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in IUCLID Calculator the oral NOAEL in the rat mg/kg/day *1/1.35 mg/m3 inhalation NOAEC for the general population (based on 60 kg bodyweight rather than 70 kg for workers).

AF for dose response relationship:

1

Justification:

There was a clear dose response in the study.

AF for differences in duration of exposure:

2

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC.

AF for other interspecies differences:

2.5

Justification:

ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.

AF for intraspecies differences:

10

Justification:

ECHA guidance recommends a factor of 10 for intraspecies differences for the general population.

AF for the quality of the whole database:

1

Justification:

While the DNEL is based on a read across substance, the read across substance is considered to be a worst case and will not be less toxic than Ethanol, 2,2’-iminobis-N-tallow alkyl derivatives, N-oxides. Therefore a factor of 1 was used.

AF for remaining uncertainties:

1

Justification:

All uncertainties are already included so a factor of 1 is applied.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.15 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:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption. So the Oral NOAEL can be used also as the dermal repeat dose NOAEL as the basis for calculating Dermal DNELs.

AF for dose response relationship:

1

Justification:

There is a clear dose response so a factor of 1 is used.

AF for differences in duration of exposure:

2

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA guidance recommends as factor of 4 for Allometric scaling from effects in the rat to humans, to compensate for the different metabolic rates.

AF for other interspecies differences:

2.5

Justification:

ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.

AF for intraspecies differences:

10

Justification:

ECHA guidance recommends a factor of 10 for intraspecies differences for the general population.

AF for the quality of the whole database:

1

Justification:

While the DNEL is based on a read across substance, the read across substance is considered to be a worst case and will not be less toxic than Ethanol, 2,2’-iminobis-N-tallow alkyl derivatives, N-oxides. Therefore a factor of 1 was used.

AF for remaining uncertainties:

1

Justification:

All uncertainties are already included so a factor of 1 is applied.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.15 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:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There is no route to route extrapolation as the NOAEL is from an oral study in rats and ECHA assumes equal absorption via the oral and dermal routes so no modification of the dose descriptor. This is a conservative approach

AF for dose response relationship:

1

Justification:

There was a clear dose response so a factor of 1 is used.

AF for differences in duration of exposure:

2

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA guidance recommends as factor of 4 for Allometric scaling from effects in the rat to humans, to compensate for the different metabolic rates.

AF for other interspecies differences:

2.5

Justification:

ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.

AF for intraspecies differences:

10

Justification:

ECHA guidance recommends a factor of 10 for intraspecies differences for the general population.

AF for the quality of the whole database:

1

Justification:

While the DNEL is based on a read across substance, the read across substance is considered to be a worst case and will not be less toxic than Ethanol, 2,2’-iminobis-N-tallow alkyl derivatives, N-oxides. Therefore a factor of 1 was used.

AF for remaining uncertainties:

1

Justification:

All uncertainties are already included so a factor of 1 is applied.

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 information available for Ethanol, 2,2’-iminobis-N-tallow alkyl derivatives, N-oxides and the read across sources 2,2’-(octadec-9-enylimino)diethanol and Ethanol, 2.2’-iminobis,-N-tallow alkyl derivatives are consistent. Adverse effects were mainly seen at local effects in the gastrointestinal tract including irritation to the fore stomach and foamy macrophages. There were no apparent systemic adverse effects, these local effects leading to decreased bodyweight and bodyweight gain in the 150mg/kg bodyweight /day top dose groups assumed to be secondary to the local effects seen in the gastrointestinal tract. The consistency in the effects and the NOAEL values together with the similarities in structure, in particular in their carbon chain distribution are sufficient support for the read across used. Therefore the DNELs calculated based on the read across NOAEL will provide adequate protection for the general population from any possibly systemic effects.