Reaction mass of 2-(methylamino)ethanol, compound with sulphur dioxide and bis[(2-hydroxyethyl)ammonium] sulphite

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

other: NOAEL

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Overall assessment factor (AF):

30

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.7 mg/m³

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:

0.84 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

120

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.84 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

120

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Reaction mass of bis(2-hydroxyethanaminium) sulfite and 2-(methylamino)ethanol - oxosulfane oxide (1:1) is a liquid consisting of N-methylethanolamine (21 %), monoethanolamine (24.6 %), sulfur dioxide (35 %), and water (20 %).

The NOAEL of the OECD 422 guideline study performed for N-methylethanolamine as the leading toxphor was used for the derivation of the DNEL. This NOAEL was set at 50 mg/kg based on kidney effects.

For the derivation of the inhalative long-term DNEL, the starting point had to be modified according to Chapter R.8 of the REACH Guidance. Here, a correction for absorption differences and activity driven differences of respiratory volumes in workers compared to workers in rest was added to receive a starting point of 88.15 mg/m3. Additionally, an overall assessment factor of 30 was established: 6 for time extrapolation and 5 for intraspecies variability. No interspecies factor was used due to the modification of the starting point. Thus, applying these assessment factors, a health-based occupational exposure limit of 3 mg/m3 is recommended for Reaction mass of bis(2-hydroxyethanaminium) sulfite and 2-(methylamino)ethanol - oxosulfane oxide (1:1).

In addition, several occupational exposure limits (OEL) exist for N-methylethanolamine, monoethanolamine, and sulfur dioxide. For N-methylethanolamine the Danish OEL is set at 9 mg/m3, for monoethanolamine the German MAK-value is set at 5.1 mg/m3 and for sulfur dioxide the German MAK-value is set at 2.7 mg/m3. All three substances are characterized by their high alkaline pH-values and corrosivity which had to be taken into account for the assessment of local effects such as respiratory irritation and for the derivation of an OEL. Reaction mass of bis(2-hydroxyethanaminium) sulfite and 2-(methylamino)ethanol - oxosulfane oxide (1:1) in contrast does not have corrosive properties. Additionally, the portions of each of the substances of the substance are between 21 % and 35 % which thus would lead to 3-5fold higher OELs taking into account the dilution factors.

For that reason, a DNEL of 3 mg/m3 is determined with which health hazard effects and risk are considered to be adequately controlled.

 

Long-term – inhalation, local/systemic effects (based on the OECD 422 study in rats)

 

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 50 mg/kg	The NOAEL was based on kidney effects.
Step 2) Modification of starting point	1/0.38*100/100*6.7/10	According to Chapter R.8 of REACH Guidance, correction for absorption differences and for activity driven differences of respiratory volumes in workers compared to workers in rest.
Modified dose-descriptor	88.15 mg/m^3
Step 3) Assessment factors
Interspecies	1	No factor for allometric scaling is needed due to the correction of the starting point
Intraspecies	5	Default assessment factor for workers
Exposure duration	6	Default assessment factor, extrapolation from subacute to chronic
Dose response	1	Starting point=NOAEL, therefore no correction
Quality of database	1	GLP-guideline study
DNEL	Value
	88.15 / (1 x 5 x 6 x 1 x 1) = 3 mg/m^3

 

Short term inhalation DNEL (workers)

For the derivation of a short term DNEL, the DNEL of long-term local and systemic effects was exceeded by a factor of 2.5 leading to a value of 7.7 mg/m3. The factor of 2.5 is based on the respective molecular weights/portions of each substance in the reaction mass and the OELs. In detail, N-methylethanolamine, monoethanolamine, and sulfur dioxide all have similar molecular weights: 64 g/mol, 61 g/mol and 75 g/mol, respectively. SO2 has the lowest OEL with a value of 2.7 mg/m3. This value was established by MAK commission and has an exceeding factor of 1. This OEL was used to derive a DNEL in consideration of the portion of SO2 in the reaction mass and without exceeding the factor of 1. Reaction mass of bis(2-hydroxyethanaminium) sulfite and 2-(methylamino)ethanol - oxosulfane oxide (1:1) contains 35 % of SO2 meaning that the OEL of 2.7 has to be multiplied with a value of 2.8 (100 %/35%) leading to a value of 7.7 mg/m3.

Long-term – dermal, systemic effects (based on the OECD 422 study in rats)

For the derivation of dermal long-term systemic DNEL, the starting point had to be modified. Here, a correction for absorption differences (assumed: oral: 100 %; dermal 50 %) was added to receive a starting point of 100 mg/kg. Additionally, an overall assessment factor of 120 was established: 4 for interspecies differences, 6 for time extrapolation and 5 for intraspecies variability. Thus, applying these assessment factors, a health-based occupational exposure limit of 0.84 mg/kg is recommended for Reaction mass of bis(2-hydroxyethanaminium) sulfite and 2-(methylamino)ethanol - oxosulfane oxide (1:1).

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 50 mg/kg	The NOAEL was based on kidney effects.
Step 2) Modification of starting point	100/50	An oral absorption of 100 %, and a dermal absorption of 50 % is assumed.
Modified dose-descriptor	100 mg/kg
Step 3) Assessment factors
Interspecies	4	Default assessment factor for interspecies differences
Intraspecies	5	Default assessment factor for workers
Exposure duration	6	Default assessment factor, extrapolation from subacute to chronic
Dose response	1	Starting point=NOAEL, therefore no correction
Quality of database	1	GLP-guideline study
DNEL	Value
	100 / (4 x 5 x 6 x 1 x 1) = 0.84 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 Reaction mass of bis(2-hydroxyethanaminium) sulfite and 2-(methylamino)ethanol - oxosulfane oxide (1:1). General population is not exposed via inhalation, dermal or oral route. Therefore no DNEL is calculated for the general population.