Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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

Long-term – inhalation, local/systemic effects (based on the 28 days inhalation study in rats)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 10 mg/m3

The exposure of rats to Monoethanolamine caused concentration-related lesions in larynx, trachea and lung. No histopathological effects were seen in any other organ outside the respiratory tract. The NOAEC for local effect was the lowest tested concentration of 10 mg/m3under the current test conditions. The NOAEC for systemic toxicity is the highest concentration of 150 mg/m3.

Step 2) Modification of starting point

1

 

 

 

 

 

According to the REACH guidance, time scaling is not appropriate when the toxic effect is mainly driven by the exposure concentration;

 

Correction for activity is not neccesary becaues the effect is mainly driven by a local mechanism and the corrosive properties of the substance on the larynx and on the trachea. Due to the fact that the rat is an obligatory nose breather the teat-species is in this case over-predictive.No modification of the starting point is applied.

Modified dose-descriptor

10 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No factor for allometric scaling is needed in case of inhalation exposure.Furthermore, the factor for remaining uncertainties is not needed as the rat is a more sensitive species for inhalation exposure and an obligatory nose breather.

Intraspecies

 

 

3

 

Using a reduced factor of 3 is justified because the critical effect is a local effect that is hardly, if at all, determined by toxicodynamics and kinetics. Absorption, distribution and elimination play no/a minor role.

Local effects are largely concentration-dependent whereas exposure time and enzyme polymorphisms are of minor importance in such cases.

Due to the fact that the local effects are driven by local exposure peaks and are not supposed to worsen with time and considering the rat is over-predictive in this case, a joint assessment factor of 3 is applied for intraspecies differences and exposure duration correction.

Exposure duration

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

10 / (1 x 3 x 1 x 1) =3.3 mg/m3

 

Long-term – dermal, systemic effects (based on the 28 days inhalation study in rats)

Using the inhalation study as starting point, the following DNEL is derived:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 150 mg/m3

No systemic effects were observed after inhalation exposure up to 150 mg/m3 for 28 days.

Step 2) Modification of starting point

0.29

 

 

 

100/37.5

A 6 h respiratory volume of 0.29 m3/kg bw for rats was used for conversion into NOAEL upon dermal exposure.

 

Correction for absorption: 100% absorption upon inhalation exposure; 37.5% absorption is assumed for dermal exposure.

Modified dose-descriptor

150 x 0.29 x (100/37.5) = 116 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4 x 1

Assessment factor for allometric scaling. As no effects were observed up to the highest concentration tested, the factor for remaining uncertainties is not applied.

Intraspecies

5

Default assessment factor

Exposure duration

6

The key study is a 28 days inhalation study.

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

116 / (4 x 1 x 5 x 6 x 1 x 1) = 1 mg/kg bw/day

 

(Taking the dermal NOAEL for maternal toxicity (systemic effects) from the developmental toxicity study with rats (Liberacki et al, 1996) as starting point, i.e., 75 mg/kg bw/day, a DNEL of 1.5 mg/kg bw/day (75 / (4 x 2.5 x 5 x 1 x 1) = 1.5 mg/kg bw/day) is calculated)

 

It has to be noted that this is a conservative approach.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Since 3 -Aminopropan-1-ol is used at industrial and professional domains only, no exposure of the general population is expected. Therefore, no DNELs for the general population were calculated.