Ethanol, 2,2'-iminobis-, N-C12-18-alkyl derivs.

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.59 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

62.5

Dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

37.03 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.

AF for dose response relationship:

1

Justification:

Effects show a clear dose response

AF for differences in duration of exposure:

5

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28 Day study are calculated using an assessment factor of 6 for extrapolation of the
study duration to chronic exposure. This compares to a factor of 2 when extrapolation from a 90-day study to chronic exposure. As the NOAEL is from an OECD422 study where the duration for the males was ca. 46 days and for females ca. 60 days the assessment factor has been reduced to 5 due to the significant extended exposure compared to a 28-day study.

AF for interspecies differences (allometric scaling):

1

Justification:

No additional factor as 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:

Data used is based on testing of 2, 2’-(C12-18 evennumbered alkyl imino) diethanol CAS No 71786-60-2 in a Klimisch 1 validity OECD422 Repeat dose and developmental toxicity screening study.

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:

medium 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)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.17 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

250

Dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

42 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. As the original oral study included 7-day a week dosing, an adjustment to the NOAEL can be made for the 5 day a week worker exposure. This is achieved by dividing the study NOAEL by 5/7 or 0.714286.

AF for dose response relationship:

1

Justification:

Effects show a clear dose response

AF for differences in duration of exposure:

5

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a
NOAEL from a 28 Day study are calculated using an assessment factor of 6 for extrapolation of the study duration to chronic exposure. This compares to a factor of 2 when extrapolation from a 90-day study to chronic exposure. As the NOAEL is from an OECD422 study where the duration for the males was ca. 46 days and for females ca. 60 days the assessment factor has been reduced to 5 due to the significant extended exposure compared to a 28-day study

AF for interspecies differences (allometric scaling):

4

Justification:

A factor of 4 is applied based on ECHA guidance for allometric scaling of data from rats to humans

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 an additional factor of 5 for the intraspecies differences between workers therefore a factor of 5 has been applied.

AF for the quality of the whole database:

1

Justification:

Data used is based on testing of 2, 2’-(C12-18 evennumbered alkyl imino) diethanol CAS No 71786-60-2 in a Klimisch 1 validity OECD422 Repeat dose and developmental toxicity screening study.

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:

medium 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:

0.09 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

125

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:

Effects show a clear dose response

AF for differences in duration of exposure:

5

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28 Day study are calculated using an assessment factor of 6 for extrapolation of the
study duration to chronic exposure. This compares to a factor of 2 when extrapolation from a 90-day study to chronic exposure. As the NOAEL is from an OECD422 study where the duration for the males was ca. 46 days and for females ca. 60 days the assessment factor has been reduced to 5 due to the significant extended exposure compared to a 28-day study.

AF for interspecies differences (allometric scaling):

1

Justification:

No additional factor as 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 an additional factor of 10 for the intraspecies differences between members of the general population, therefore a factor of 10 has been applied.

AF for the quality of the whole database:

1

Justification:

Data used is based on testing of 2, 2’-(C12-18 evennumbered alkyl imino) diethanol CAS No 71786-60-2 in a Klimisch 1 validity OECD422 Repeat dose and developmental toxicity screening study.

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:

medium 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)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.06 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

500

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. No adjustment for duration of exposure was used as the rats were dosed 7 days a week and the general population could also be exposed 7 days a week.

AF for dose response relationship:

1

Justification:

Effects show a clear dose response

AF for differences in duration of exposure:

5

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28 Day study are calculated using an assessment factor of 6 for extrapolation of the
study duration to chronic exposure. This compares to a factor of 2 when extrapolation from a 90-day study to chronic exposure. As the NOAEL is from an OECD422 study where the duration for the males was ca. 46 days and for females ca. 60 days the assessment factor has been reduced to 5 due to the significant extended exposure compared to a 28-day study.

AF for interspecies differences (allometric scaling):

4

Justification:

A factor of 4 is applied based on ECHA guidance for allometric scaling of data from rats to humans

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 an additional factor of 10 for the intraspecies differences between members of the general population, therefore a factor of 10 has been applied.

AF for the quality of the whole database:

1

Justification:

Data used is based on testing of 2, 2’-(C12-18 evennumbered alkyl imino) diethanol CAS No 71786-60-2 in a Klimisch 1 validity OECD422 Repeat dose and developmental toxicity screening study.

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:

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

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:

0.06 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

500

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:

Test data in rats is for the same oral route of exposure as the general population. No adjustment for duration of exposure was used as the rats were dosed 7 days a week and the general population could also be exposed 7 days a week.

AF for dose response relationship:

1

Justification:

Effects show a clear dose response

AF for differences in duration of exposure:

5

Justification:

ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28 Day study are calculated using an assessment factor of 6 for extrapolation of the
study duration to chronic exposure. This compares to a factor of 2 when extrapolation from a 90-day study to chronic exposure. As the NOAEL is from an OECD422 study where the duration for the males was ca. 46 days and for females ca. 60 days the assessment factor has been reduced to 5 due to the significant extended exposure compared to a 28-day study.

AF for interspecies differences (allometric scaling):

4

Justification:

A factor of 4 is applied based on ECHA guidance for allometric scaling of data from rats to humans

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 an additional factor of 10 for the intraspecies differences between members of the general population, therefore a factor of 10 has been applied.

AF for the quality of the whole database:

1

Justification:

Data used is based on testing of 2, 2’-(C12-18 evennumbered alkyl imino) diethanol CAS No 71786-60-2 in a Klimisch 1 validity OECD422 Repeat dose and developmental toxicity screening study.

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)