Amines, polyethylenepoly-, tetraethylenepentamine fraction

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.82 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):

30

Dose descriptor starting point:

LOAEL

Value:

50 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

24.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral LOAEL observed in a chronic repeated dose oral toxicity study (Yanagisawa, 1998).

To correct the interspecies difference between rat and human the lowest observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= LOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h) * (7 days of exposure rat/5 days of exposure worker)

= 50 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (20%/100%) * 0.67 m³ * 1.4= 24.7 mg/m³

For intestinal absorption a figure of 20% has been estimated (based on rat data). Inhalation absorption was estimated to be 100% (no data).

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

Thus, the corrected starting point for workers was 24.7 mg/m³ for inhalation.

AF for dose response relationship:

3

Justification:

The dose descriptor starting point is based on a LOAEL. 50 mg/kg bw TETA.2HCL was a NOAEL in females but a LOAEL in males.

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable

AF for other interspecies differences:

1

Justification:

rats and dogs showed similar NOAELs following 26 weeks of exposure; mice showed a 2-times higher NOAEL at a 2-times shorter duration (13 weeks), indicating that interspecies effect concentrations are small if at all

AF for intraspecies differences:

5

Justification:

Default value according to ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

no additional assessment factor is needed

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

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

Dose descriptor:

NOAEC

Value:

1.25 mg/m³

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

1

Justification:

does not apply for local dermal effects

AF for interspecies differences (allometric scaling):

1

Justification:

no allometric scaling needed because of local effects

AF for other interspecies differences:

1

Justification:

the mechanism of effects is direct chemical/pH reactivity, thus no further kinetic and dynamic considerations apply

AF for intraspecies differences:

5

Justification:

default AF for workers

AF for the quality of the whole database:

1

Justification:

no additional assessment factor is needed

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

high 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:

0.14 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):

60

Dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

8.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral LOAEL observed in a chronic repeated dose oral toxicity study (Yanagisawa, 1998).

To correct the interspecies difference between rat and human the lowest observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for general population:

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

= 50 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (20%/100%) = 8.7 mg/m³

For intestinal absorption a figure of 20% has been estimated (based on rat data). Inhalation absorption was estimated to be 100% (no data).

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

Thus, the corrected starting point for workers was 8.7 mg/m³ for inhalation.

AF for dose response relationship:

3

Justification:

The dose descriptor starting point is based on a LOAEL. 50 mg/kg bw TETA.2HCL was a NOAEL in females but a LOAEL in males.

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable

AF for other interspecies differences:

1

Justification:

rats and dogs showed similar NOAELs following 26 weeks of exposure; mice showed a 2-times higher NOAEL at a 2-times shorter duration (13 weeks), indicating that interspecies effect concentrations are small if at all

AF for intraspecies differences:

10

Justification:

Default value according to ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

no additional assessment factor is needed

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

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20.8 µg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

60

Dose descriptor:

NOAEC

Value:

1.25 mg/m³

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

6

Justification:

AF for sub-acute to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

no allometric scaling needed because of local effects

AF for other interspecies differences:

1

Justification:

the mechanism of effects is direct chemical/pH reactivity, thus no further kinetic and dynamic considerations apply

AF for intraspecies differences:

10

Justification:

default AF for general population

AF for the quality of the whole database:

1

Justification:

no additional assessment factor is needed

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.21 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):

240

Dose descriptor starting point:

LOAEL

Value:

50 mg/kg bw/day

AF for dose response relationship:

3

Justification:

The dose descriptor starting point is based on a LOAEL. 50 mg/kg bw TETA.2HCL was a NOAEL in females but a LOAEL in males.

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

The experimental animal was a rat.

AF for other interspecies differences:

1

Justification:

rats and dogs showed similar NOAELs following 26 weeks of exposure; mice showed a 2-times higher NOAEL at a 2-times shorter duration (13 weeks), indicating that interspecies effect concentrations are small if at all

AF for intraspecies differences:

10

Justification:

Default value according to ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

no additional assessment factor is needed

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)