2-dimethylaminoethyl methacrylate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23.94 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

other: ECHA (2012) with substance-specific adaptations

Overall assessment factor (AF):

18

Dose descriptor starting point:

NOAEC

Value:

643 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

431 mg/m³

Explanation for the modification of the dose descriptor starting point:

Correction for rat standard breathing volume, 8 hrs (ECHA R.8, 2012): 0.38 m³/kg

^{Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3) is required (ECHA R.8, 2012): 6.7 m3/10 m3}

 

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

6

Justification:

The NOAEL is based on a sub-acute study. ECHA specifies the AF for extrapolation from sub-acute to chronic with 6.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Known and widely scientifically accepted mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) metabolising methacrylates in the same way in all vertebrate species. All methacrylates are metabolized to methacrylic acid and the corresponding alcohol. These metabolites are broken down via physiological metabolic pathways. Hence, the AF of 1 is sufficient.

AF for intraspecies differences:

3

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 3 is sufficiently conservative.

AF for the quality of the whole database:

1

Justification:

The key study is of high quality, being rated K2. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

There is no further assessment factor needed for remaining uncertainties, because all of them are addressed by the AFs above.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

47.87 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: ECHA (2012) and substance-specific adaptations

Overall assessment factor (AF):

9

Dose descriptor starting point:

LOAEC

Value:

431 mg/m³

AF for dose response relationship:

3

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

1

Justification:

Concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat’s ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and human have to be taken into account.

AF for intraspecies differences:

3

Justification:

Systemic effects in the repeated dose study with rats were minimal and restricted to slow body weight gain probably due to local irritation of nose and eyes. Especially for irritation of the respiratory epithelium rodents like the rat are more sensitive than humans.
Furthermore, based on the results from the repeated dose inhalation study and from other toxicity studies the test substance is considered to be a local irritant without much specific systemic toxicity, and not much variation of the irritant effect in human workers is expected. Therefore, an assessment factor of 3 for intraspecies variations is considered to be sufficient.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.3 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA (2012) with substance-specific adaptations

Overall assessment factor (AF):

24

Dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Oral to dermal extrapolation is performed as explained in ECHA R. 8, 2012.

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

2

Justification:

The NOAEL is based on a sub-chronic study. ECHA specifies the AF for extrapolation from sub-chronic to chronic with 2.

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling rat to humans (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Known and widely scientifically accepted mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) metabolising methacrylates in the same way in all vertebrate species. All methacrylates are metabolized to methacrylic acid and the corresponding alcohol. These metabolites are broken down via physiological metabolic pathways.
Hence, the AF of 1 is sufficient.

AF for intraspecies differences:

3

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 3 is sufficiently conservative.

AF for the quality of the whole database:

1

Justification:

The key study is of high quality, being rated K1. No adjustment is required.)

AF for remaining uncertainties:

1

Justification:

There is no further assessment factor needed for remaining uncertainties, because all of them are addressed by the AFs above.

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

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)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21.43 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

other: ECHA (2012) with substance-specific adaptations

Overall assessment factor (AF):

30

Dose descriptor starting point:

NOAEC

Value:

643 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

643 mg/m³

Explanation for the modification of the dose descriptor starting point:

According to ECHA guidance (2012), the modification of the dose descriptor starting point is not necessary for DNEL derivation for general population inhalation. 

 

 

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

6

Justification:

The NOAEL is based on a sub-acute study. ECHA specifies the AF for extrapolation from sub-acute to chronic with 6.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Known and widely scientifically accepted mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) metabolising methacrylates in the same way in all vertebrate species. All methacrylates are metabolized to methacrylic acid and the corresponding alcohol. These metabolites are broken down via physiological metabolic pathways. Hence, the AF of 1 is sufficient.

AF for intraspecies differences:

5

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 3 is sufficiently conservative.

AF for the quality of the whole database:

1

Justification:

The key study is of high quality, being rated K2. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

There is no further assessment factor needed for remaining uncertainties, because all of them are addressed by the AFs above.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Most sensitive endpoint:

irritation (respiratory tract)

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

12.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA (2012) with substance-specific adaptations

Overall assessment factor (AF):

40

Dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Oral to dermal extrapolation is performed as explaining in ECHA R8, 2012.

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

2

Justification:

The NOAEL is based on a sub-chronic study. ECHA specifies the AF for extrapolation from sub-chronic to chronic with 2.

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling rat to humans (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Known and widely scientifically accepted mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) metabolising methacrylates in the same way in all vertebrate species. All methacrylates are metabolized to methacrylic acid and the corresponding alcohol. These metabolites are broken down via physiological metabolic pathways. Hence, the AF of 1 is sufficient.

AF for intraspecies differences:

5

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 3 is sufficiently conservative.

AF for the quality of the whole database:

1

Justification:

The key study is of high quality, being rated K1. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

There is no further assessment factor needed for remaining uncertainties, because all of them are addressed by the AFs above.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

12.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA (2012) with substance-specific adaptations

Overall assessment factor (AF):

40

Dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Modification of the dose descriptor starting point is not necessary since it originates from an oral rat study. 

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

2

Justification:

The NOAEL is based on a sub-chronic study. ECHA specifies the AF for extrapolation from sub-chronic to chronic with 2.

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling rat to humans (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Known and widely scientifically accepted mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) metabolising methacrylates in the same way in all vertebrate species. All methacrylates are metabolized to methacrylic acid and the corresponding alcohol. These metabolites are broken down via physiological metabolic pathways. Hence, the AF of 1 is sufficient.

AF for intraspecies differences:

5

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 3 is sufficiently conservative.

AF for the quality of the whole database:

1

Justification:

The key study is of high quality, being rated K1. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

There is no further assessment factor needed for remaining uncertainties, because all of them are addressed by the AFs above.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected