1-aminopropan-2-ol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.6 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:

56 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

89 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation repeated dose toxicity study is available. Thus, extrapolation from a OECD 408 oral study with DIPA is performed: NOAEL = 100 mg/kg bw/d. Correction of the NOAEL DIPA to the NOAEL MIPA based on the molecular weights: 100 mg/kg bw/d * (75.11 g/mol / 133.19 g/mol) = 56 mg/kg bw/d.

Based on the REACH R.8 guidance an inhalation volume for rats of 0.38 m3/kg for 8 hr exposure is used. NOAEL to NOAEC conversion: NOAEC rats = 56 mg/kg/d / 0.38 m3/kg =  147 mg/m3.

No oral absorption data are available for MIPA; hence data of DIPA are used (90% oral absorption). 100% absorption is assumed for inhalation: NOAEC rats = 147 mg/m3 x 90/100 = 133 mg/m3. Correction factor for increased inhalation volume during work: NOAEC worker, 8hr = 6.7 m3/ 10m3 x 132 mg/m3 = 89 mg/m3.

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

2

Justification:

Extrapolation to chronic exposure based on a sub-chronic toxicity study.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation.
(already handled in the correction of the NOAEL)

AF for other interspecies differences:

2.5

Justification:

Default assessment factor.

AF for intraspecies differences:

5

Justification:

Default assessment factor.

AF for the quality of the whole database:

1

Justification:

The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic 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

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)

Additional information - workers

Long-term – inhalation, systemic effects

Supporting the DNEL derivation with the structurally similar DIPA, a 28d repeated dose toxicity study based on hydrochloride salt of MIPA (CAS 7780 -04 -3, OECD 422 study) in rats is available. The derived DNEL value is 4.3 mg/m3 which is in line with the derived value above of 3.6 mg/m3.

NOAEL: 300 mg/kg bw/day; Systemic toxicity of the test substance for the F0 parental males based on some indications for a mild anemic process.

An 8 h respiratory volume of 0.38 m3/kg bw for rats was used for conversion into NOAEL upon inhalation exposure. Correction for activity driven differences of respiratory volumes in workers compared to workers in rest: 6.7 m3/10 m3. No oral absorption data are available for MIPA; hence, data of DIPA are used (90% oral absorption). 100% absorption is assumed for inhalation.

Modification of starting point: 0.38 m3/kg bw x 6.7 m3/10 m3 x 90/100. Correction for MW (75.1/111.6) between MIPA and the hydrochloride salt of MIPA.

Modified dose-descriptor: 300 x 6.7 x 90 x 75.1/ (0.38 x 10 x 100 x 111.6) = 320 mg/m3

Assessment factors:

- Interspecies (other): 2.5 (No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation.)

- Intraspecies: 5 (Default assessment factor)

- Exposure duration: 6 (Default assessment factor for e sub-acute to chronic duration of the study.)

- Dose response: 1

- Quality of database: 1

DNEL-Value:  320 mg/m3 / (2.5 x 5 x 6 x 1 x 1) = 4.3 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.88 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

44.13 mg/m³

Explanation for the modification of the dose descriptor starting point:

Modified DD starting point: NOAEC = 100 mg/kg *75.11/133.19 /1.15 m3/kg *90/100
- NOAEL (90d, oral, DIPA) = 100 mg/kg bw/d.
- *75.1/133.19: Correction for MW (75.1 g/mol / 133.19 g/mol) between MIPA and DIPA. 
- /1.15 m3/kg: A 24 h respiratory volume of 1.15 m3/kg bw for rats was used for conversion into NOAEL upon inhalation exposure.
- *90/100: No oral absorption data are available for MIPA; hence, data of TIPA are used (90% oral absorption). 100% absorption is assumed for inhalation. 

AF for dose response relationship:

1

Justification:

default, OECD study with 3 doses

AF for differences in duration of exposure:

2

Justification:

default for sub-chronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

default after extrapolation from oral to inhalation exposure route.

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

default

AF for the quality of the whole database:

1

Justification:

default

AF for remaining uncertainties:

1

Justification:

default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.88 mg/m³

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.51 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

101.51 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Modified DD starting point: NOAEL = 100 mg/kg *75.11/133.19 *90/50
- NOAEL (90d, oral, DIPA) = 100 mg/kg bw/d.
- *75.1/133.19: Correction for MW (75.1 g/mol / 133.19 g/mol) between MIPA and DIPA. 
- *90/50: No oral absorption data are available for MIPA; hence, data of TIPA are used (90% oral absorption). 50% absorption is assumed by default for dermal exposure. 

AF for dose response relationship:

1

Justification:

default, OECD study with 3 doses

AF for differences in duration of exposure:

2

Justification:

default, sub-chronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

default (rat --> human)

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

default, general population

AF for the quality of the whole database:

1

Justification:

default

AF for remaining uncertainties:

1

Justification:

default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.51 mg/kg bw/day

DNEL related information

DNEL extrapolated from long term DNEL

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:

0.28 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:

56.39 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Modified DD starting point: NOAEL = 100 mg/kg *75.11/133.19
- NOAEL (90d, oral, DIPA) = 100 mg/kg bw/d.
- *75.1/133.19: Correction for MW (75.1 g/mol / 133.19 g/mol) between MIPA and DIPA. 

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

2

Justification:

Default sub-chronic to chronic factor 2

AF for interspecies differences (allometric scaling):

4

Justification:

The standard interspecies factor for rats is 4.

AF for other interspecies differences:

2.5

Justification:

The factor for other interspecies differences, i.e. toxicokinetic/-dynamic differences.

AF for intraspecies differences:

10

Justification:

Default assessment factor for the general population.

AF for the quality of the whole database:

1

Justification:

The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties:

1

Justification:

No remaining unvertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)