2-dibutylaminoethanol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.22 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

75

Dose descriptor starting point:

NOAEC

Value:

236.3 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

166.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

Modified starting point: 236.3 mg/m3 *6h/8h *7d/5d *6.7m3/10m3 = 166.2 mg/m3 (ECHA GD Chapter R.8: Characterisation of dose [concentration]-response for human health, section R.8.4.2; v2.1, Nov 2012)

AF for dose response relationship:

1

Justification:

default for OECD TG study with 3 doses (ECHA GD R.8.4.3.1)

AF for differences in duration of exposure:

6

Justification:

default for subacute to chronic (ECHA GD R.8.4.3.1)

AF for interspecies differences (allometric scaling):

1

Justification:

no allometric scaling, if expressed in concentration (e.g. mg/m3 in air) and/or already scaled according to the allometric principle (ECHA GD R.8.4.3.1)

AF for other interspecies differences:

2.5

Justification:

default (ECHA GD 8.4.3.1)

AF for intraspecies differences:

5

Justification:

default (ECHA GD 8.4.3.1)

AF for the quality of the whole database:

1

Justification:

sufficient and reliable studies (ECHA GD R.8.4.3.1)

AF for remaining uncertainties:

1

Justification:

default (ECHA GD 8.4.3.1)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.5 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

9

Dose descriptor:

other: modified dose descriptor, taking into account no/light work but no time scaling: 20.6 mg/m3 *6.7 m3/10 m3 (ECHA GD R.8.4.2)

Value:

13.8 mg/m³

AF for dose response relationship:

1

Justification:

default for OECD TG study with 3 doses (ECHA GD R.8.4.3.1)

AF for differences in duration of exposure:

3

Justification:

In line with ECHA GD R.8.4.3.1, the default factor of 6 for subacute to chronic extrapolation is not considered justified, because an impact of the exposure duration on the observed local effects is considered to be minor. Neither higher incidences nor more severity of the effects in the nasal cavity were observed in the high dose animals of the 90d study compared to the 14d DRF study. Furthermore, only one mid dose female of 90d study showed minimal effects in the nasal cavity, which were not observed in the 14d DRF study. However, an impact cannot fully be excluded and thus, a factor of 3 is used.

AF for interspecies differences (allometric scaling):

3

Justification:

Concerning local effects allometric scaling is not necessary. However, Brüning et al., 2014 suggested an interspecies extrapolating factor (iEF) of 3 for extrapolating from animal data concerning local sensory irriating effects without reliable human data, unless individual data argue for a substance-specific approach. [Sensory irritation as a basis for setting occupational exposure limits, Arch Toxicol (2014) 88: 1855-1879].

AF for other interspecies differences:

1

Justification:

An additional assessment factor for other interspecies differences is no considered necessary due to the iEF = 3, suggested by Brüning et al., 2014.

AF for intraspecies differences:

1

Justification:

An additional assessment factor for intraspecies differences of workers is no considered necessary, due to the iEF = 3, suggested by Brüning et al., 2014; taking into account controlled human volunteer studies and epidemiological studies conducted in the worker environment.
Besides, according to the ECHA GD R.8 (v2.1, Nov 2012; section R.8.4.2) and the ECETOC TR110 [Guidance on assessment factors to derive a DNEL", Technical Report No. 110, ECETOC, 2010.] an extrapolation from animal data to exposure of workers results in the same overall inter-/intraspecies factor of 3:
- interspecies AF = 1, due to no allometric scaling for local effects, and if expressed in concentration and/or already scaled (ECHA GD R.8.4.3.1, ECETOC TR110);
- other interspecies AF = 1, according to ECETOC TR110 the other interspecies and intraspecies differences are interdependent and therefore this aspect is already taken into account in the intraspecies factor of 3 (ECETOC TR110);
- intraspecies AF = 3, the same factor for local effects is proposed in the ECETOC TR110 as for systemic effects, based on a detailed literature review.

AF for the quality of the whole database:

1

Justification:

sufficient and reliable studies (ECHA GD R.8.4.3.1)

AF for remaining uncertainties:

1

Justification:

default (ECHA GD R.8.4.3.1)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 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):

100

Dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

modified starting point: 1* oral NOAEL (ECHA GD R.8.4.2)

AF for dose response relationship:

1

Justification:

default for OECD TG study with 3 doses (ECHA GD R.8.4.3.1)

AF for differences in duration of exposure:

2

Justification:

default for subchronic to chronic (ECHA GD R.8.4.3.1)

AF for interspecies differences (allometric scaling):

4

Justification:

default for rat to human (ECHA GD 8.4.3.1)

AF for other interspecies differences:

2.5

Justification:

default (ECHA GD 8.4.3.1)

AF for intraspecies differences:

5

Justification:

default (ECHA GD 8.4.3.1)

AF for the quality of the whole database:

1

Justification:

sufficient and reliable studies (ECHA GD R.8.4.3.1)

AF for remaining uncertainties:

1

Justification:

default (ECHA GD R.8.4.3.1)

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)

Additional information - workers

Point of departure

-       for inhalation long-term exposure – systemic effects:

The systemic NOAEC from a combined repeated dose toxicity study with the reproduction / developmental toxicity screening test in rats via inhalation conducted according to OECD 422 (BASF SE, 2013) was identified as the appropriate starting point for a systemic DNEL derivation for long-term exposure following inhalation. The NOAEC for general, systemic toxicity of the test substance was 236.3 mg/m³/day for rats which was the highest dose tested. The reduced FC, BW and BWG were considered to be secondary to the local irritating effects and thus, not taken into account for the systemic DNEL, as a local DNEL was also derived.

-       for inhalation long-term exposure – local effects:

The local NOAEC from a combined repeated dose toxicity study with the reproduction / developmental toxicity screening test in rats via inhalation conducted according to OECD 422 (BASF SE, 2013) was identified as the appropriate starting point for local DNEL derivation for long-term exposure following inhalation. The NOAEC for local irritation of respiratory tract was 20.6 mg/m³/day for rats.

-       for dermal long-term exposure – systemic effects

The NOAEL from an 90d Study in rats with gavage administration in corn oil according to OECD 408 (BASF SE, 2019) was identified as the appropriate starting point for systemic DNEL derivation for long-term dermal exposure.  The oral NOAEL in rats was 50 mg/kg bw/d, based on adverse effects observed in the kidney at 150 mg/kg bw/d.

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

Most sensitive endpoint:

irritation (respiratory tract)

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

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

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

Most sensitive endpoint:

irritation (respiratory tract)

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:

DNEL (Derived No Effect Level)

Value:

0.25 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

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are reliable experimental data on oral repeated exposure. No route to route extrapolation is needed.

AF for dose response relationship:

1

Justification:

Default value

AF for differences in duration of exposure:

2

Justification:

Default value for time extrapolation from subchronic to chronic study

AF for interspecies differences (allometric scaling):

4

Justification:

Default value concerning allometric scaling rat - human

AF for other interspecies differences:

2.5

Justification:

Default

AF for intraspecies differences:

10

Justification:

The default value for "consumer" is used

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and reliable (GLP Guideline study)

AF for remaining uncertainties:

1

Justification:

Default

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

For an assessment man via environment, an oral, systemic, long-term DNEL for the general population might be neccessary. However, as no consumer uses are known, no further DNELs for the general population were derived.

Oral long-term exposure – systemic effects:

The systemic NOAEL from a 90 day GLP repeated dose toxicity study in rats via oral administration conducted according to OECD 408 (BASF SE, 2019) was identified as the appropriate starting point for a systemic DNEL derivation for long-term exposure following oral administration. The NOAEL for general, systemic toxicity of the test substance was 50 mg/kg bw/day for rats. The assessment factors were applied according to the "Guidance on information requirements and chemical safety assessment, Chapter R.8, v 2.1, Nov. 2012.