Monoethanolamine oleate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

146.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

41.7 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

24

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. In the present case, DNELs have been derived according to the ECETOC guidance (ECETOC, Technical Report No. 110, 2010).

No information on absoprtion of monoethanolamine oleate is available. In accordance with Chapter R.8 of REACH Guidance on information requirements and chemical safety assesment, a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) is proposed to be used in the case of oral-to-inhalation extrapolation. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation. These default factors will be taken forward to DNEL derivation.

The substance does not have to be classified for acute toxicity and therefore derivation of a DNEL_acute is not necessary. The substance is not irritating to skin, but irritating to eyes. However, it is not possible to derive a DNEL for eye irritation on the basis of the available data. It is necessary to stipulate risk management measures that prevent the occurrence of eye irritation.

The substance is not sensitizing, therefore no DNEL for sensitization needs to be derived.

Monoethanolamine oleate is assessed as being non-mutagenic, non-carcinogenic and non-toxic to reproduction and development; therefore no DNELs have been derived for these endpoints.

For repeated dose toxicity, a NOAEL of 1000 mg/kg bw/day, based on the read-across with monoethanolamine, will be taken forward to DNEL derivation. This value is based on the results of the oral 2 -generation reproductive toxicity study with monoethanolamine, in which signs of systemic toxicity were observed in parental females at the highest dose level of 1000 mg/kg bw/day, manifested as reduced food consumption and/or body weight gain during gestation and lactation. In F1 animals, at 300 mg/kg bw/day and 1000 mg/kg bw/day statistically significant increases of absolute and relative kidney weights were observed; however, these increases were not accompanied by histopathological changes. In F0 and F1 males at 1000 mg/kg bw/day absolute and relative organ weights of cauda epididymidis and epididymides were statistically significantly decreased. Prostate weight and the number of homogenization resistant caudal epididymal sperm were statistically significantly decreased in the F0 males. These findings were not accompanied by histopathological changes. Based on this, a NOAEL of 300 mg/kg bw/day was established for general toxicity of monoethanolamine in the study. Applying a correction for molecular weight, a NOAEL of 300× 343.31/61.08 = 1686 mg/kg bw/day can be calculated for monoethanolamine oleate. This value is above the limit dose value of 1000 mg/kg bw/day recommended by OECD Guidelines. As the calculated value for NOAEL is excessively high and may exceed the maximal tolerated physiological dose, the OECD guideline limit value of 1000 mg/kg bw/day will be taken forward for risk assessment and will be used for DNEL derivation.

Long-term – inhalation, systemic effects (based on 2 -generation reproductive toxicity study in rats)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 1000 mg/kg bw/day	Read-across from monoethanolamine; based on reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males;
Step 2) Modification of starting point	2         0.38 m^3/kg bw           6.7 m^3/10 m^3	The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation.   Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2).   Correction for activity driven differences of respiratory volumes in workers compared to workers in rest.
Modified dose-descriptor	1000 / 2 / 0.38 x (6.7/10) = 881.5 mg/m^3
Step 3) Assessment factors
Interspecies	1	No assessment factor for allometric scaling needs to be applied in case of oral to inhalation route-to-route extrapolation
Intraspecies	3	Default assessment factor for workers
Exposure duration	1	As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required.
Dose response	1	A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL
Quality of database	2	Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed.
DNEL	Value
	881.5 / (1 x 3 x 1 x 1 x 2) = 146.9 mg/m^3

 

 

Long-term – dermal, systemic effects (based on 2-generation reproductive toxicity study in rats)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 1000 mg/kg bw/day	Read-across from monoethanolamine; based on reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males;
Step 2) Modification of starting point	1	According to Chapter R.8 of the REACH Guidance on information requirements and chemical safety assessment, a default factor of 1 is proposed for the extrapolation from oral to dermal route of absorption
Modified dose-descriptor	1000 x 1 = 1000 mg/kg bw/day
Step 3) Assessment factors
Interspecies	4	Assessment factor for allometric scaling in case of a study with rats
Intraspecies	3	Default assessment factor for workers
Exposure duration	1	As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required
Dose response	1	A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL
Quality of database	2	Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed.
DNEL	Value
	1000 / (4 x 3 x 1 x 1 x 2) = 41.7 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

43.5 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. In the present case, DNELs have been derived according to the ECETOC guidance (ECETOC, Technical Report No. 110, 2010).

No information on absoprtion of monoethanolamine oleate is available. In accordance with Chapter R.8 of REACH Guidance on information requirements and chemical safety assesment,a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) is proposed to be used in the case of oral-to-inhalation extrapolation. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation. These default factors will be taken forward to DNEL derivation.

The substance does not have to be classified for acute toxicity and therefore derivation of a DNEL_acuteis not necessary. The substance is not irritating to skin, but irritating to eyes. However, it is not possible to derive a DNEL for eye irritation on the basis of the available data. It is necessary to stipulate risk management measures that prevent the occurrence of eye irritation.

The substance is not sensitizing, therefore no DNEL for sensitization needs to be derived.

Monoethanolamine oleate is assessed as being non-mutagenic, non-carcinogenic and non-toxic to reproduction and development; therefore no DNELs have been derived for these endpoints.

For repeated dose toxicity, a NOAEL of 1000 mg/kg bw/day, based on the read-across with monoethanolamine, will be taken forward to DNEL derivation. This value is based on the results of the oral 2 -generation reproductive toxicity study with monoethanolamine, in whichsigns of systemic toxicity were observed in parental females at the highest dose level of 1000 mg/kg bw/day, manifested as reduced food consumption and/or body weight gain during gestation and lactation. In F1 animals, at 300 mg/kg bw/day and 1000 mg/kg bw/day statistically significant increases of absolute and relative kidney weights were observed; however, these increases were not accompanied by histopathological changes.In F0 and F1 males at 1000 mg/kg bw/day absolute and relative organ weights of cauda epididymidis and epididymides were statistically significantly decreased. Prostate weight and the number of homogenization resistant caudal epididymal sperm were statistically significantly decreased in the F0 males. These findings were not accompanied by histopathological changes. Based on this, a NOAEL of 300 mg/kg bw/day was established for general toxicity of monoethanolamine in the study. Applying a correction for molecular weight, a NOAEL of 300× 343.31/61.08 = 1686 mg/kg bw/day can be calculated for monoethanolamine oleate. This value is above the limit dose value of 1000 mg/kg bw/day recommended by OECD Guidelines.As the calculated value for NOAEL is excessively high and may exceed the maximal tolerated physiological dose, the OECD guideline limit value of 1000 mg/kg bw/day will be taken forward for risk assessment and will be used for DNEL derivation.

Long-term – inhalation, systemic effects (based on 2 -generation reproductive toxicity study in rats)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 1000 mg/kg bw/day	Based on read-across from monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males.
Step 2) Modification of starting point	2         1.15 m^3/kg bw	The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation.   Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2).
Modified dose-descriptor	1000 / (2 x 1.15) = 434.8 mg/m^3
Step 3) Assessment factors
Interspecies	1	No assessment factor for allometric scaling needs to be applied in case of oral to inhalation route-to-route extrapolation
Intraspecies	5	Default assessment factor for general population
Exposure duration	1	As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required.
Dose response	1	A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL
Quality of database	2	Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed.
DNEL	Value
	434.8 / (1 x 5 x 1 x 1 x 2) = 43.5 mg/m^3

 

 

Long-term – dermal, systemic effects (based on 2-generation reproductive toxicity study in rats)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 1000 mg/kg bw/day	Based on read-across from monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreased absolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males.
Step 2) Modification of starting point	1	According to Chapter R.8 of the REACH Guidance on information requirements and chemical safety assessment, a default factor of 1 is proposed for the extrapolation from oral to dermal route of absorption
Modified dose-descriptor	1000 x 1 = 1000 mg/kg bw/day
Step 3) Assessment factors
Interspecies	4	Assessment factor for allometric scaling in case of a study with rats
Intraspecies	5	Default assessment factor for general population
Exposure duration	1	As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required
Dose response	1	A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL
Quality of database	2	Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed.
DNEL	Value

1000 / (4 x 5 x 1 x 1 x 2) =25 mg/kg bw/day

Long-term – inhalation, systemic effects (based on 2 -generation reproductive toxicity study in rats)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 1000 mg/kg bw/day	Based on read-across from monoethanolamine; based on the reduced food consumption and/or body weight gain in females during gestation and lactation; statistically significantly decreasedabsolute and relative organ weights of cauda epididymidis and epididymides, prostate weight and the number of homogenization resistant caudal epididymal sperm in males.
Step 2) Modification of starting point	not applicable
Step 3) Assessment factors
Interspecies	4	Assessment factor for allometric scaling in case of a study with rats
Intraspecies	5	Default assessment factor for general population
Exposure duration	1	As the NOAEL was established in a 2 -generation study, no correction for exposure duration is required
Dose response	1	A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL
Quality of database	2	Due to the use of read-across a provisional use of an additional safety factor of 2 is proposed.
DNEL	Value

1000 / (4 x 5 x 1 x 1 x 2) = 25 mg/kg bw/day