Isodecyl methacrylate

Toxicological Summary

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:

Factor 2 forOral 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 m^3;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 NOEL is reliable. No adjustment 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 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 diferences 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:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

The derivation of the DNEL for Isodecyl methacrylate is based on the analogue substance 2 -Ethylhexyl methacrylate. The repeated dose toxicity of the latter is considered as the worst case. Increasing molecular weight of the alkyl methacrylate esters with an alcohol moiety chain length of C8 and above is leading to lower toxicity due to decreasing volatility, bioavailability and slower metabolism.

Long-term exposure (inhalation) - local effects

Based on phys.-chem- properties and toxicokinetic information, the inhalation pathway is not considered a relevant route of exposure for Isodecyl methacrylate.

Long-term exposure (inhalation) -systemic effects

In a subchronic 90-day gavage study in rats with 2-Ethylhexyl methacrylate 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 2008).
Intraspecies	3	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.)
Exposure duration	2	The NOAEC is based on a 13-week study. AF for extrapolation fromSub-chronic to chronic (ECHA 2008).
Dose response	1	The NOAEC is reliable. No adjustment is required.
Quality of database	1	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.
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.

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.

The substance is not added to food. Additionally, since the analogue substance 2 -Ethylhexyl methacrylate exhibits a low BCF(37) in fish, is readily biodegradable (failing 10-day window) and rapidly metabolised in rodents and humans, secondary poisoning by the oral route is unlikely to be a relevant route of exposure.