Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC 2010
Overall assessment factor (AF):
47.1
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
15.28 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no data for n-octyl methacrylate available.

Read across to 2 -Ethylhexyl methacrylate:

Factor 2 for oral to inhalation route-to-route extrapolation (ECHA R8, 2012)

Factor 0.38 m³/kg as correction for rat standard breathing volume (ECHA R8, 2012)

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3; ECHA R8, 2012).

AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
The NOAEC is based on a 13-week study. AF for extrapolation from Sub-chronic to chronic (ECHA R8, 2012).
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 R8, 2012).
AF for other interspecies differences:
1
Justification:
Not justified due to known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases, tricarboxylic acid cycle).
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 5 by ECETOC (2010) is sufficiently conservative for workers.)
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality, being rated K1. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
Default value of 2.5 for remaining differences not justified (ECETOC, 2010).
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:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC 2010
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
The NOAEC is based on a 13-week study. AF for extrapolation from Sub-chronic to chronic (ECHA R8, 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4 (ECHA R8, 2012).
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, tricarboxylic acid cycle) makes a lower variability likely, hence the AF of 5 by 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:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

There are no data for n-octyl methacrylate available.

Read across to 2 -Ethylhexyl methacrylate:

Since 2-EHMA is of low acute toxicity with the median lethal dose values (LD50) being significantly greater than 2000 mg/kg by oral and dermal routes and a vapour pressure that is sufficiently low to prevent acute toxicity the derivation of DNELs for systemic long-term exposure is considered sufficiently protective.

Acute & long-term dermal exposure - local effects:

2-EHMA is considered as weak sensitizer, however a quantitative DNEL cannot derived for skin sensitization, even in the presence of a LLNA due to its negative results. Due to low potency of the substance, moderate hazard according to ECHA guiance part E is assigned for acute and long-term local effects.

Long-term exposure (inhalation) - local effects

2-Ethylhexyl methacrylate has a low vapour pressure and there is a valid oral subchronic toxicity study. Like with MMA, local effects resulting from the hydrolysis of the ester to MAA might be expected following inhalation exposure. In the case of MMA this has been shown to be due to the localised concentration of non-specific esterases in nasal olfactory tissues. Data with MMA and n-BMA indicate that the NOEC for this local effect increases with increasing ester chain length within the category. For MMA the NOAEC in rats is 25 ppm while for n-BMA the NOAEC for this lesion is already 310 ppm (LOAEC was 952 ppm) in a subacute study. With 2-EHMA with a saturated vapour density of 50-100 ppm at ambient temperature (64 ppm at 20 °C) it is unlikely that concentrations could ever be reached which cause this effect.

Long-term exposure (inhalation) - systemic effects

In a subchronic 90-day gavage study in rats with 2-EHMA, the lead effects observed were signs of general systemic toxicity at 360 mg/kg body weight/day in both males and females. 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC:120 mg/kg bw/d

NOAEC for rats,for 13 weeks by the oral route

Step 2) Modification of starting point

2

 

0.38 m³/kg

 

10 m3/6.7 m3

Oral to inhalation route-to-route extrapolation (ECHA R8, 2012)

Correction for rat standard breathing volume (ECHA R8, 2012)

-Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3) is required  

(ECHA R8, 2012)

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes. 2.5 for remaining differences not justified (ECETOC, 2010).

Intraspecies

3

Default AF (ECETOC, 2010)

Exposure duration

2

The NOAEC is based on a 13-week study. AF for extrapolation fromSub-chronic to chronic  

(ECHA R8, 2012)

.

Dose response

1

The NOAEC is reliable. No adjustment is required.

Quality of database

1

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

DNEL

Value

Based upon a NOAEC of 120 mg/kg bw/d for rats,for 13 weeks by the oral route.

 Using a total factor (POD modifier and AF) of 47.1 (2 / 0.38x 10/6.7 m³ x 1 x 3 x 2)a DNELlong-term,workerof 2.5mg/m³ is derived.

Long-term exposure (oral/dermal exposure) - systemic effects

In a subchronic 90-day gavage study in rats with 2-EHMA the lead effects observed were signs of non-specific, general systemic toxicity at 360 mg/kg body weight/day in both males and females.

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 120 mg/kg bw/d

NOAEC for rats,for 13 weeks

Step 2) Modification of starting point

1


No adjustment is necessary.

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling rat to humans AF 4 (ECHA R8, 2012)

. 2.5 for remaining differences not justified (ECETOC, 2010).

Intraspecies

3

Default AF (ECETOC, 2010)

Exposure duration

2

The NOAEC is based on a 13-week study. AF for extrapolation fromSub-chronic to chronic  (ECHA R8, 2012)

.

Dose response

1

The NOAEC is reliable. No adjustment is required.

Quality of database

1

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

DNEL

Value

NOAEC: 120 mg/kg bw/d

Using a total factor (POD modifier and AF) of 24 (1 x 1 x 4 x 3 x 2 x 1 x 1)a DNELlong-term,workerof 5.0mg/kg bw/d is derived.

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:
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

General Population - Hazard via oral 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There are only professional and industrial uses of the monomer. For the general population the only known uses are all with (co-)polymers only. As the toxicity of the monomers is comparable, exposure to residual monomer which has been determined as safe in the case with the other members of the lower alkyl methacrylate category is also regarded as safe in the case of n-octyl methacrylate.

 

The substance is not added to food; Additionally, since the substance exhibits a low BCF(37) in fish, is readily biodegradable and rapidly metabolised in rodents and humans, secondary poisoning by the oral route is unlikely to be a relevant route of exposure.