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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33 mg/kg bw/day
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
40
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
40

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

(2 -Hydroxyethyl)ammonium nitrate is the salt of 2 -Aminoethanol (14 %) and nitric acid (26 %) in water (60 %).

The NOAEC of the inhalation study performed for 2-Aminoethanol as the leading toxophor was used for the derivation of the DNEL. This NOAEC was set at 10 mg/m3 based on local effects. As no systemic effects were observed after inhalation exposure up to the highest concentration tested, 150 mg/m3, for 28 days, derivation of a long-term DNEL based on this NOAEC is a conservative approach with which health hazard effects and risk are considered to be adequately controlled.

For the derivation of the inhalative long-term DNEL, no correction of the starting point had to be performed since 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 test-species is in this case over-predictive. According to the REACH guidance, time scaling is not appropriate when the toxic effect is mainly driven by the exposure concentration. No factor for allometric scaling is needed in case of inhalation route. A factor of 3 is used for intraspecies variation. Absorption, distribution and elimination play no/a minor role since local effects are largely concentration-dependent whereas exposure time and enzyme polymorphisms are of minor importance. Thus, applying these assessment factors, a health-based occupational exposure limit of 3.3 mg/m3 can be calculated. Considering the mass proportions (content of 2-Aminoethanol: 14 %), a DNEL of ca. 23 mg/m3 is obtained for (2 -Hydroxyethyl)ammonium nitrate. In addition, a German occupational exposure limits (OEL) exists for monoethanolamine which is set at 5.1 mg/m3 with an exceeding factor of 2. Considering once again the mass proportions, a health-based DNEL of ca. 35 mg/m3 would be obtained. These values exceed the recommended general nuisance level which is set at 10 mg/m3.

The effects which occurred in the OECD 416 performed with Monoethanolamin-hydrochlorid regarding reproductive toxicity are also covered by a DNEL of 10 mg/m3. In case of using the received NOAEL of 300 mg/kg, a correction for absorption differences and activity driven differences of respiratory volumes in workers compared to workers in rest would need to be added to receive a starting point of 528.95 mg/m3. Additionally, an overall assessment factor of 25 would be established: 2 for time extrapolation and 5 for intraspecies variability and 2.5 for remaining differences. Thus, applying these assessment factors, a health-based occupational exposure limit of ca. 21 mg/m3 would be received. With regard to mass proportions, this value would even be a very conservative DNEL.

For that reason, a DNEL of 10 mg/m3 is recommended for (2 -Hydroxyethyl)ammonium nitrate. This level is considered to be sufficiently protective from possible local and systemic effects.

 

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 MEA 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/m3 under the current test conditions. The NOAEC for systemic toxicity is the highest concentration of 150 mg/m3.

Step 2) Modification of starting point

1

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.

Exposure duration

1

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

Dose response

1

Starting point=NOAEC, therefore no correction

Quality of database

1

GLP-guideline study

DNEL

Value

 2-Aminoethanol

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

(2 -Hydroxyethyl)ammonium nitrate

3.3 mg/m3 * 7.14 (dilution factor) = 23 mg/m3

 

Long-term – dermal, systemic effects (based on the OECD 416 study in rats)

For the derivation of a dermal DNEL, the NOAEL received from the oral OECD 416 was used. Existing dermal studies from Liberacki (1996) did not show any systemic effects but strong local skin effects based on the corrosive properties of 2-Aminoethanol. The corrosive properties are not present in (2 -Hydroxyethyl)ammonium nitrate. This is why data from the OECD 416 performed with 2 -Aminoethanol hydrochloride do more precisely reflect the systemic properties of the salt (2 -Hydroxyethyl)ammonium nitrate.

For the derivation of dermal long-term systemic DNEL, the starting point had to be modified. Here, absorption of oral: 100 % and dermal: 100 % (slight irritating properties which probably enhance uptake through the skin) was assumed. The starting point was 300 mg/kg. Additionally, an overall assessment factor of 40 was established: 4 for interspecies differences, 2 for time extrapolation and 5 for intraspecies variability. Thus, applying these assessment factors, a health-based value of 4.7 mg/kg was received. Considering the mass proportion, a health-based DNEL of 33 mg/kg is recommended for (2-Hydroxyethyl)ammonium nitrate.

 

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 300 mg/kg

The NOAEL was based on systemic effects received from the OECD 416.

Step 2) Modification of starting point

100/100

An oral and dermal absorption of 100 % is assumed.

Modified dose-descriptor

300 mg/kg

Step 3) Assessment factors

 

 

Interspecies

4

Default assessment factor for interspecies differences

Intraspecies

  

5

Default assessment factor for workers 

Exposure duration

2

Default assessment factor, extrapolation from subchronic to chronic

Dose response

1

Starting point=NOAEL, therefore no correction

Quality of database

1

GLP-guideline study

DNEL

Value

 2-Aminoethanol

300 / (4 x 5 x 2 x 1 x 1) = 7.5 mg/kg (corresponds to 4.7 mg/kg 2-Aminoethanol under consideration of mass proportions)

(2 -Hydroxyethyl)ammonium nitrate

33 mg/kg

 

 

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There are only industrial uses for morpholinium toluene-4-sulphonate. General population is not exposed via inhalation, dermal or oral route. Therefore no DNEL is calculated for the general population.