Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
44.08 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):
10
Dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
440.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

The corrected starting point is a NOAEC of 440.8 mg/m³.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling for inhalation
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
DNEL (Derived No Effect Level)
Value:
7.81 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):
40
Dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
312.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Estimated 80% dermal absorption rate. Oral NOAEL divided by 0.8 results in dermal NOAEL of 312.5 mg/kg bw.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The long-term systemic DNELs (dermal, inhalation) for workers have been derived from a 90-day oral (gavage) toxicitry study with APD. The NOAEL in this study was 250 m/kg bw/day. This dose level was chosen as the starting point for deriving the DNELs. No DNELs have been derived for the short-term dermal and inhalation exposure for workers, as it is assumed that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure

To convert the oral NOAEL into an inhalation NOAEC, the oral NOAEL (250 m/kg bw) for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg) and adaptation to an 8-hour working day. Therefore, the corrected starting point is a NOAEC of 440.8 mg/m³. No quantitative dose-response data are available for local short-term effects on skin and respiratory tract of APD. The most sensitive local endpoint is eye corrosion.

In general, assessment factors (AF) recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, Version 2, December, 2010) were used when applicable to derive the DNELs. Several AFs for which there is additional information were refined. The difference in metabolic rate between humans and the test species has been taken into account, where relevant. The AF for remaining interspecies differences has been set at 1, as the toxicokinetic data indicates that APD will not be metabolised. Due to its polarity and size, APD will mainly be excreted unmetabolised via the urine (see toxicokinetics).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.87 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):
20
Dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
217.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

To convert the oral NOAEL into an inhalatory NOAEC, the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for 24 h exposure). Therefore, the corrected starting point is a NOAEC of 217.4 mg/m³.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling for inhalation.
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.91 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):
80
Dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
312.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Estimated 80% dermal absorption rate. Oral NOAEL divided by 0.8 results in dermal NOAEL of 312.5 mg/kg bw.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.125 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):
80
Dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
10
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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)

Additional information - General Population

The general population is usually not exposed to 2-amino-1,3–propanediol (APD), based on its identified uses. However, the long-term consumer DNEL for oral, dermal and inhalation systemic effects have been derived.

The long-term systemic DNELs (oral dermal, inhalation) for the general population have been derived from a 90-day oral (gavage) toxicitry study with APD. The NOAEL in this study was 250 mg/kg bw/day. This dose level was chosen as the starting point for deriving the DNEL for all exposure routes. To convert the oral NOAEL into an inhalation NOAEC, the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for 24 h exposure). Therefore, the corrected starting point is a NOAEC of 217.4 mg/m³. The absorption via the inhalation route is considered to be in the same order of magnitude as via the oral route. To convert the oral NOAEL [mg/kg bw/day] into a dermal NOAEL [mg/kg bw/day], the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. European Chemicals Agency, Version 2, December 2010). For APD a dermal absorption of 80% was calculated using QSAR and the available physico-chemical properties. Based on practical experience, the dermal absorption of 80% has to be regarded as a worst-case scenario: A solution of APD is usually used in applications where the pH will be closer to neutral. As a consequence, APD will predominantly be present in an ionised form which will not easily penetrate the skin.

No DNELs have been derived for the short-term dermal and inhalation exposure for the general population, as it is assumed that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure. No quantitative dose-response data are available for local short-term effects on skin and respiratory tract of APD. The most sensitive local endpoint is eye corrosion.

 

In general, assessment factors (AF) recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, Version 2, December 2010) were used when applicable to derive the DNELs. Several AFs for which there is additional information were refined. The difference in metabolic rate between humans and the test species has been taken into account, where relevant. The AF for remaining interspecies differences has been set at 1, as the toxicokinetic data indicates that APD will not be metabolised. Due to its polarity and size, APD will mainly be excreted unmetabolised via the urine (see toxicokinetics).