Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
41.66 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no dermal repeated dose toxicity study is available
AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
AF for extrapolation from sub-chronic to chronic (ECHA 2008).
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4 (ECHA 2008).
AF for other interspecies differences:
1
Justification:
The substances are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.
AF for intraspecies differences:
3
Justification:
Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricaboxylic acid cycle) makes a lower variability likely, hence the AF of 3 by ECHA (2008) and ECETOC (2010) is sufficiently conservative for workers.
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Inhalation DNELs:

Due to the extremely low vapour pressure of the long-chain alkyl methacrylate esters (C12 – C22), inhalation exposure is not considered as relevant.

Systemic DNEL for acute exposure:

As there is no evidence for critical effects from acute oral and dermal toxicity studies, the chronic DNEL will be protective against this endpoint.

Local DNELs for acute and long-term exposure:

No critical local effects were identified, the long-chain alkyl methacrylate esters are only slightly irritating to skin. The chronic DNEL will be protective against this endpoint.

 

Derivation of systemic DNEL for long-term exposure

On the basis of the NOAEL at the highest administered dose of 1000 mg/kg body weight / day in the OECD TG 422 repeated dose toxicity and toxicity to reproduction study with dodecyl methacrylate in rats (read-across), a total assessment factor of 24 was used to calculate the dermal DNEL value for systemic effects after long-term exposure of 41.66 mg/kg bw/day.

 

Discussion of the applied assessment factors in detail (AF):

Interspecies factor - allometric scaling: assessment factor 4 (default value for Rat – Human)

Interspecies factor – remaining differences: The limited dermal absorption of the long-chain methacrylate esters was demonstrated in absorption studies with the C12 ester dodecyl methacrylate (0.26 % over 26 hrs in whole rat skin, details see dermal absorption). There is further evidence for low dermal toxicity from animal tests (LD50 in rabbits > 3000 mg/kg).Therefore, the interspecies factor of 2.5 for remaining differences was not applied.

Intraspecies factor – workers: a factor of 3 for workers was taken (ECHA, 2008 and ECETOC, 2010).

Exposure Duration - from subchronic to chronic an assessment factor of 2 was taken by default.

Further assessment factors have not to be considered.

The total assessment Factor is as follows: 4 x 3 x 2 = 24

NOAEL: 1000 mg/kg/d

DNEL (workers, long-term, systemic): 41.66 mg/kg/d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no dermal repeated dose toxicity study is available
AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
AF for extrapolation from sub-chronic to chronic (ECHA 2008).
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4 (ECHA 2008).
AF for other interspecies differences:
1
Justification:
The substances are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.
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 5 by ECHA (2008) and ECETOC (2010) is sufficiently conservative for the general population.
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Inhalation DNELs:

Due to the extremely low vapour pressure of the long-chain alkyl methacrylate esters (C12 – C22), inhalation exposure is not considered as relevant.

Systemic DNEL for acute exposure:

As there is no evidence for critical effects from acute oral and dermal toxicity studies, the chronic DNEL will be protective against this endpoint.

Local DNELs for acute and long-term exposure:

No critical local effects were identified, the long-chain alkyl methacrylate esters are only slightly irritating to skin. The chronic DNEL will be protective against this endpoint.

 

Derivation of systemic DNEL for long-term exposure

On the basis of the NOAEL at the highest administered dose of 1000 mg/kg body weight / day in the OECD TG 422 repeated dose toxicity and toxicity to reproduction study with dodecyl methacrylate in rats (read-across), a total assessment factor of 40 was used to calculate the dermal DNEL value for systemic effects after long-term exposure of 25 mg/kg bw/day.

 

Discussion of the applied assessment factors in detail (AF):

Interspecies factor - allometric scaling: assessment factor 4 (default value for Rat – Human)

Interspecies factor – remaining differences: The limited dermal absorption of the long-chain methacrylate esters was demonstrated in absorption studies with the C12 ester dodecyl methacrylate (0.26 % over 26 hrs in whole rat skin, details see dermal absorption). There is further evidence for low dermal toxicity from animal tests (LD50 in rabbits > 3000 mg/kg). Therefore, the interspecies factor of 2.5 for remaining differences was not applied.

Intraspecies factor – workers: a factor of 5 for general population was taken (ECHA, 2008 and ECETOC, 2010).

Exposure Duration - from subchronic to chronic an assessment factor of 2 was taken by default.

Further assessment factors have not to be considered.

The total assessment Factor is as follows: 4 x 5 x 2 = 40

NOAEL: 1000 mg/kg/d

  

DNEL (general population, long-term, systemic): 25 mg/kg/d