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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
other: NAEC
Value:
23.51 mg/m³
AF for dose response relationship:
2
Justification:
Route-to-route extrapolation: oral to inhalation
AF for differences in duration of exposure:
4
Justification:
Subacute (56 d) to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Additional interspecies factor for toxicodynamic/toxicokinetic differences
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
2
Justification:
A screening study is used for DNEL derivation
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.042 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
320
Modified dose descriptor starting point:
NOAEL
Value:
13.3 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
4
Justification:
Subacute (56 d) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human allometric scaling
AF for other interspecies differences:
2.5
Justification:
Additional interspecies factor for toxicodynamic/toxicokinetic differences
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
2
Justification:
A screening study is used for DNEL derivation
AF for remaining uncertainties:
0.8
Justification:
80% dermal absorption
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

No DNELs have been derived for the short-term dermal and inhalation exposure of 2 -methoxyethyl acrylate (2 -MEA) for workers, 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, eye and respiratory tract of 2 -MEA.

The starting point for DNEL derivation is a lowest observed adverse effect level (LOAEL) of 40 mg/kg bw/day obtained from a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD 422 (de Raaf-Beekhuijzen, 2012). Male and female rats were treated with 2-MEA by oral gavage at dose levels of 40, 100 and 250/150 mg/kg bw/day.The males were exposed for 31-35 days and the females were exposed for 42-56 days with the test substance.

In this study,2-MEA led to parental, reproduction and developmental toxicity at all dose levels. Therefore, a no-observed adverse effect level (NOAEL) could not be determined. The LOAEL for systemic toxicity/reproduction toxicity/developmental toxicity is 40 mg/kg bw/day.

As the starting point for the DNEL calculation is a LOAEL, extrapolation of the LOAEL to a NOAEL is considered. For the dose-response relationship an assessment factor of 3 is used(Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November, 2012). Therefore, the dose descriptor starting point is a NOAEL of 13.3 mg/kg bw/day.

According to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November, 2012”, the oral NOAEL needs to be converted into an inhalatory NAEC:the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38m³/kg for 8 h exposure). Additionally, it should be taken into account that during 8 hours light activity at work the respiratory rate becomes higher (10m³/person) than standard (6.7m³/person).Considering these differences, the corrected starting point is a NAEC of 23.51 mg/m³.In the absence of route-specific information, a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in case of oral-to-inhalation extrapolation is included. The inclusion of factor 2 means that 50% (instead of 100%) absorption is assumed for oral absorption, and 100% for inhalation(Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November 2012).

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 [concentration]-response for human health, Version 2.1, November, 2012). For 2-MEA a dermal absorption of 80% was calculated using QSAR and the available physico-chemical properties. A QSAR based modelling published by Potts and Guy (1992), taking into account molecular weight and log Kow, estimated a dermal permeability constant Kp of 1.26E-03 cm/h. Similar to the approach taken by Kroes et al. (2007), the maximum flux Imax (Imax = Kp [cm/h] x water solubility [mg/cm³]) was calculated, resulting in dermal absorption of 181.9 µg/cm²/h 2-MEA. Usually, this value is considered as indicator for a dermal absorption of 80% (Mostert and Goergens, 2011).

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 2.1, November, 2012) were used when applicable to derive the DNEL. The difference in metabolic rate between humans and the test species has been taken into account, where relevant. An AF for exposure duration is applied to take into account the difference between experimental exposure duration and the exposure duration for the worker.In the combined oral repeated dose toxicity with the reproduction/developmental toxicity screening test (de Raaf-Beekhuijzen, 2012) that is used to derive the long-term exposure DNELs, female rats were exposed for at least 56 days. Based on the exposure duration of 56 days and a publication of Batke et al. (2011), an AF of 4 has been chosen in this case, as it reflects the exposure duration accurately.

 

References not cited in the IUCLID:

Batke et al., 2011, Evaluation of time extrapolation factors based on the database RepDose. Toxicol Lett, 205(2):122 -129

Kroes, R. et al. (2007) Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food Chem. Toxicol. 45, 2533–2562

Mostert, V. and Goergens, A. (2011) Dermal DNEL setting: using QSAR predictions for dermal absorption for a refined route-to-route extrapolation. Society of Toxicology, Annual Meeting, http://www.toxicology.org/AI/PUB/Toxicologist11.pdf, ISSN 1096-6080, 120(2): 107

Potts, R. and Guy, R. (1992) Predicting skin permeability. Pharm. Res. 9(5): 663-669

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.029 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
other: NAEC
Value:
11.6 mg/m³
AF for dose response relationship:
2
Justification:
Route-to-route extrapolation: oral to inhalation
AF for differences in duration of exposure:
4
Justification:
Subacute (56 d) to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Additional interspecies factor for toxicodynamic/toxicokinetic differences
AF for intraspecies differences:
10
Justification:
Default value for the general population
AF for the quality of the whole database:
2
Justification:
A screening study is used for DNEL derivation
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.021 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
640
Modified dose descriptor starting point:
NOAEL
Value:
13.3 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
4
Justification:
Subacute (56 d) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human allometric scaling
AF for other interspecies differences:
2.5
Justification:
Additional interspecies factor for toxicodynamic/toxicokinetic differences
AF for intraspecies differences:
10
Justification:
Default value for the general population
AF for the quality of the whole database:
2
Justification:
A screening study is used for DNEL derivation
AF for remaining uncertainties:
0.8
Justification:
80% dermal absorption
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.017 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
800
Modified dose descriptor starting point:
NOAEL
Value:
13.3 mg/kg bw/day
AF for differences in duration of exposure:
4
Justification:
Subacute (56 d) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human allometric scaling
AF for other interspecies differences:
2.5
Justification:
Additional interspecies factor for toxicodynamic/toxicokinetic differences
AF for intraspecies differences:
10
Justification:
Default value for the general population
AF for the quality of the whole database:
2
Justification:
A screening study is used for DNEL derivation
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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 not exposed to 2 -methoxyethyl acrylate (2 -MEA), based on the identified uses. The industrial use of the 2-MEA monomer is as a chemical intermediate in the production of homopolymers and copolymers with other monomers. Residual monomer concentrations of 2 -MEA in polymers are very low in consumer products (< 100 ppm; < 0.01%). Therefore, considerable consumer exposure is not to be expected.

However, the long-term consumer DNELs for oral, dermal and inhalation systemic effects have been derived. No DNELs have been derived for the short-term dermal, oral and inhalation exposure of 2 -MEA 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, eye and respiratory tract of 2 -MEA.

The starting point for DNEL derivation is a lowest observed effect level (LOAEL) of 40 mg/kg bw/day obtained from a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD 422 (de Raaf-Beekhuijzen, 2012). Male and female rats were treated with 2-MEA by oral gavage at dose levels of 40, 100 and 250/150 mg/kg bw/day. The males were exposed for 31-35 days and the females were exposed for 42-56 days with the test substance.

In this study, 2-MEA led to parental, reproduction and developmental toxicity at all dose levels. Therefore, a no-observed adverse effect level (NOAEL) could not be determined. The LOAEL for systemic toxicity/reproduction toxicity/developmental toxicity is 40 mg/kg bw/day.

As the starting point for the DNEL calculation is a LOAEL, extrapolation of the LOAEL to a NOAEL is considered. For the dose-response relationship an assessment factor of 3 is used (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November, 2012). Therefore, the dose descriptor starting point is a NOAEL of 13.3 mg/kg bw/day.

According to the Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health (European Chemicals Agency, Version 2.1, November, 2013), the oral NOAEL should be converted into an inhalatory NAEC: 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 NAEC of 11.6 mg/m³. The inclusion of factor 2 means that 50% (instead of 100%) absorption is assumed for oral absorption, and 100% for inhalation (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November 2012).

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 [concentration]-response for human health, Version 2.1, November, 2012). For 2-MEA a dermal absorption of 80% was calculated using QSAR and the available physico-chemical properties. A QSAR based modelling published by Potts and Guy (1992), taking into account molecular weight and log Kow, estimated a dermal permeability constant Kp of 1.26E-03 cm/h. Similar to the approach taken by Kroes et al. (2007), the maximum flux Imax (Imax = Kp [cm/h] x water solubility [mg/cm³]) was calculated, resulting in dermal absorption of 181.9 µg/cm²/h 2-MEA. Usually, this value is considered as indicator for a dermal absorption of 80% (Mostert and Goergens, 2011).

The oral DNEL for the general population is also based on the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD 422 (de Raaf-Beekhuijzen, 2012).

As the study was performed via the oral route and the corrected NOAEL of 13.3 mg/kg bw/day can be used directly to derive the oral DNEL.

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 2.1, November, 2012) were used when applicable to derive the DNEL. The difference in metabolic rate between humans and the test species has been taken into account, where relevant. An AF for exposure duration is applied to take into account the difference between experimental exposure duration and the exposure duration for the worker. In the combined oral repeated dose toxicity with the reproduction/developmental toxicity screening test (de Raaf-Beekhuijzen, 2012) that is used to derive the long-term exposure DNELs, female rats were exposed for at least 56 days. Based on the exposure duration of 56 days and a publication of Batke et al. (2011), an AF of 4 has been chosen in this case, as it reflects the exposure duration accurately.

 

References not cited in the IUCLID:

Batke et al., 2011, Evaluation of time extrapolation factors based on the database RepDose. Toxicol Lett, 205(2):122 -129

Kroes, R. et al. (2007) Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food Chem. Toxicol. 45, 2533–2562

Mostert, V. and Goergens, A. (2011) Dermal DNEL setting: using QSAR predictions for dermal absorption for a refined route-to-route extrapolation. Society of Toxicology, Annual Meeting, http://www.toxicology.org/AI/PUB/Toxicologist11.pdf, ISSN 1096-6080, 120(2): 107

Potts, R. and Guy, R. (1992) Predicting skin permeability.Pharm. Res. 9(5): 663-669