Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-(2-aminomethylethyl)-.omega.-(2-aminomethylethoxy)-

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.29 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:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

132.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

As no long-term study on inhalation is available, route-to-route extrapolation has been performed (oral to inhalation).

The NOAEL (oral route) observed in an Extended One-Generation Reproductive Toxicity Study, performed according to OECD 443 guideline (Barnett, 2020), was used to derive a DNEL long-term, systemic effects via the inhalation route. The NOAEL was established to be 150 mg/kg bw/day. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point is 132.2 mg/m³ = 150 mg/kg bw/day x 1/(0.38 m³/kg bw/day) x 6.7 m³/10 m³ x 0.5. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure for workers). For workers, the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity).  In addition, the NOAEL needed to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%.

AF for dose response relationship:

1

Justification:

NOAEL is used as the starting point, no additional assessment factor is required

AF for differences in duration of exposure:

2

Justification:

difference in study duration, subchronic to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

covered by calculation for route-to-route extrapolation

AF for other interspecies differences:

2.5

Justification:

Default assessment factor

AF for intraspecies differences:

5

Justification:

worker population

AF for the quality of the whole database:

1

Justification:

Default assessment factor

AF for remaining uncertainties:

1

Justification:

Default assessment factor

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:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEL

Value:

250 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A 90 -day repeated dose toxicity study with dermal application of the test substance was performed according to GLP requirements and equivalent to the OECD guideline 411 (Pharmakon Research International Inc., 1990; key study, Klimisch 2). The NOAEL in this study is established at 250 mg/kg bw/day. The DNEL for long-term, systemic effects for the dermal route of exposure was derived with the NOAEL (dermal) of 250 mg/kg bw/day as dose descriptor starting point.

AF for dose response relationship:

1

Justification:

NOAEL is used as the starting point, no additional assessment factor is required.

AF for differences in duration of exposure:

2

Justification:

difference in study duration, subchronic to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

rat to human

AF for other interspecies differences:

2.5

Justification:

default assessment factor

AF for intraspecies differences:

5

Justification:

worker population

AF for the quality of the whole database:

1

Justification:

default assessment factor

AF for remaining uncertainties:

1

Justification:

default assessment factor

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

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:

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

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:

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

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

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:

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

Additional information - General Population

No consumer use is expected, therefore no hazard assessment for the general population is performed