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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
37.5 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1
Dose descriptor:
other: German MAK Value (37.5 mg/m3)
AF for dose response relationship:
1
Justification:
not required. See in Discussion for details.
AF for differences in duration of exposure:
1
Justification:
not required. See in Discussion for details.
AF for interspecies differences (allometric scaling):
1
Justification:
not required. See in Discussion for details.
AF for other interspecies differences:
1
Justification:
not required. See in Discussion for details.
AF for intraspecies differences:
1
Justification:
not required. See in Discussion for details.
AF for the quality of the whole database:
1
Justification:
not required. See in Discussion for details.
AF for remaining uncertainties:
1
Justification:
not required. See in Discussion for details.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Isodecyl acrylate is manufactured and processed within closed systems. The primary routes of industrial exposure to isodecyl acrylate are skin contact and inhalation. In an industrial setting, ingestion is not an anticipated route of exposure.

 

The data on 2-ethylhexyl acrylate, an analogue substance of isodecyl acrylate, were used for the repeated studies. Dose-level selection for long-term studies was limited by severity of local effects on the upper respiratory tract, therefore long-term exposure systemic DNELs were not calculated. 

However, a study on skin sensitisation is available on isodecyl acrylate. The substance is a skin sensitizer and a DNEL was calculated based on this study.

 

 

DNEL of 2-ethylhexyl acrylate (long-term local effect by inhalation):

In 2007 the German MAK commission determined a scientific OEL for 2-ethylhexyl acrylate of 5 ppm (37.5 mg/m3), which was confirmed as a German OEL by the regulatory authorities in 2008.

The evaluation is based on the subchronic inhalation study (BASF AG, 1989) with a NOAEC for local effects (as most sensitive parameter) at 10 ppm, at the next higher concentration of 30 ppm only marginal to mild irritation / degeneration of the olfactory epithelium in the nasal cavity was observed. The grading of those effects was the same as observed in the control animals, only the incidence was slightly increased.

Based on the mild and focal effects observed at the LOAEC of 30 ppm, also no dysfunctions of the olfactory epithelium are expected at this concentration. Because rats are obligate nose breathers, and considering physiological parameters such as respiratory minute volume and surface area of the nasal cavity / olfactory epithelium, it was calculated that the exposure of the olfactory epithelium of the rat under experimental conditions was not less than anticipated worker exposure based on increased respiratory rate under work load.

Since no short term inhalation studies are available with 2-ethylhexyl acrylate the MAK commission took data available with acrylic acid, methyl-, ethyl- and butyl acrylate which showed that only a mild enhancement of the local irritation effects were observed over time.

An intraspecies factor may be justified if an effect is linked to enzyme polymorphism however, in cases of unspecific local irritation, especially where the effects are only sequels of pH-shifts or protein denaturation, there is not much variation to be expected. According to the MAK evaluation, based on studies with ethyl acrylate examining the enzymatic activity of carboxylic esterases in the respiratory and olfactory epithelium in rats,cynomolgusmonkeys and men, it can be assumed that the ester cleavage is faster in rats than in men and monkeys (Frederick et al. 2002). Also other studies with succinic-, glutaric and adipinic acid esters showed a faster ester cleavage in the olfactory epithelium of rats compared with men and monkeys (Bogdanffy and Frame 1994), comparable results are know with methyl methacrylate (Mainwaring et al 2001). Acrylic acid is responsible for the nasal lesions caused by acrylates. It was calculated for 2 – 5 ppm ethyl acrylate that the acrylic acid burden of the olfactory epithelium in rats is by a factor 18 higher than it would be in the human olfactory epithelium (Frederick et al. 2002). Based on this data the MAK commission came to the conclusion that the olfactory epithelium of humans is less exposed than those of rats to acrylates. On the basis of the NOAEC of 10 ppm the MAK-value of 2-ethylhexyl acrylate was determined to be 5 ppm. A STEL (15 min) of 5 ppm was recommended based on a pragmatic approach of multiplying the MAK-value by a factor of 1.

This national OEL (long-term) is taken as DNEL, it is based on actual and well documented toxicological information and evaluation of health effects, in which the approach how it is derived is scientifically justified and is therefore in accordance with ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose (concentration)-response for human health (May 2008).

DNEL (long-term, local effect, inhalation) of of 2-ethylhexyl acrylate = 37.5 mg/m3

 

·        BASF AG (1989) Report: Inhalation toxicity of 2-ethylhexyl acrylate as vapor in rats (3 months study), project-no. 50I081/8502,  

·        Bogdanffy MS, Fame SR (1994), Olfactory mucosal toxicity, Integration of morphological and biochemical data in mechanistic studies; Dubasuc esters as an example.Inhalation Toxicology 6, 205-219

·        Frederick CB, Lomax LG, Black KA, Finch L, Scribner HE, Kimbel JS, Morgan KT, Subramaniam PR, Morris JB (2002) Use of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry comparisons of ester vapors. Toxicol. Appl. Pharmacol., 183, 23-40

·        Mainwaring G, Foster JR, Lund V, Green T (2001) Methyl methacrylate toxicity in rat nasal epithelium: studies of the mechanism of action and comparisons  between species.Toxicology 158, 109-118

·        MAK evaluation 2-ethylhexyl acrylate, Toxikologische arbeitsmedizinische Begründung von MAK-Werten, 42. Lieferung 2007

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.5 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
8.4
Dose descriptor:
other: German MAK Value (37.5 mg/m3)
AF for dose response relationship:
1
Justification:
not required
AF for differences in duration of exposure:
4.2
Justification:
Also the possible exposure time may be by a factor 3 (8 hrs. vs. 24 hrs) and by a factor 1.4 (5 days/week vs. 7 days/week) longer.
AF for interspecies differences (allometric scaling):
1
Justification:
not required
AF for other interspecies differences:
1
Justification:
not required
AF for intraspecies differences:
2
Justification:
according to the ECHA Guidance document the intraspecies factor is by a factor 2 higher for general population than for worker.
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
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
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
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:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Since end-use consumer products contain only trace levels of acrylic acid and esters (as a result of polymerization), consumer exposure to acrylate monomers is likely to be low (SRI, 2001).

  • SRI, 2001 . CEH Marketing Research Report, Acrylic Acid and Esters, 606 .4000A, Chemical Economics Handbook -SRI International .

Long-tern exposure systemic DNELs were not calculated because of the lack of long-term systemic effects. Dose-level selection for long-term studies was limited by severity of local effects on the upper respiratory tract.

DNEL of 2-ethylhexyl acrylate (long-term local effect by inhalation):

In 2007 the German MAK commission determined a scientific OEL for 2-ethylhexyl acrylate of 5 ppm (38 mg/m3), which was confirmed as a German OEL by the regulatory authorites in 2008.

The evaluation is based on the subchronic inhalation study (BASF AG, 1989) with a NOAEC for local effects (as most sensitive parameter) at 10 ppm, at the next higher concentration of 30 ppm only marginal to mild irritation / degeneration of the olfactory epithelium in the nasal cavity was observed. The grading of those effects was the same as observed in the control animals, only the incidence was slightly increased. Based on the mild and focal effects observed at the LOAEC of 30 ppm, also no dysfunctions of the olfactory epithelium are expected at this concentrations.

Because rats are obligate nose breathers, and considering physiological parameters such as respiratory minute volume and surface area of the nasal cavity / olfactory epithelium, it was calculated that the exposure of the olfactory epithelium of the rat under experimental conditions was not less than anticipated worker exposure based on increased respiratory rate under work load.

Since no short term inhalation studies are available with 2-ethylhexyl acrylate the MAK commission took data available with acrylic acid, methyl-, ethyl- and butyl acryate which showed that only a mild enhancement of the local irritation effects were observed over time.

An intraspecies factor may be justified if an effect is linked to enzyme polymorphism. In cases of unspecific local irritation, however, especially where the effects are only sequels of pH-shifts or protein denaturation, there is not much variation to be expected. According to the MAK evaluation, based on studies with with ethyl acrylate examining the enzymatic activity of carboxylic esterases in the respiratory and olfactory epithelium in rats, cynomolgus monkeys and men, it can be assumed that the ester cleavage is faster in rats than in men and monkeys.(Frederick et al. 2002). Also other studies with succinic-, glutaric and adipinic acid esters showed a faster ester cleavage in the olfactory epithelium of rats compared with men and monkeys (Bogdanffy and Frame 1994), comparable results are know with methyl methacrylate (Mainwaring et al 2001).

Acrylic acid is responsible for the nasal lesions caused by acrylates. It was calculated for 2 – 5 ppm ethyl acrylate that the acrylic acid burden of the olfactory epithelium in rats is by a factor 18 higher than it would be in the human olfactory epithelium (Frederick et al. 2002).

Based on this data the MAK commission came to the conclusion that the olfactory epithelium of humans is less exposed than those of rats to acrylates. On the basis of the NOAEC of 10 ppm the MAK-value of 2-ethylhexyl acrylate was determined to be 5 ppm. A STEL (15 min) of 5 ppm was recommended based on a pragmatic approach of multiplying the MAK-value by a factor of 1.

This national OEL (long-term) is taken as occupational DNEL, it is based on actual and well documented  toxicological information and evaluation of health effects, in which the approach how it is derived is scientifically justified and is therefore in accordance with ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose (concentration)-response for human health (May 2008).

This value is regarded to be safe for workers; according to the ECHA Guidance document the intraspecies factor is by a factor 2 higher for general population than for worker. Also the possible exposure time may be by a factor 3 (8 hrs. vs. 24 hrs) and by a factor 1.4 (5 days/week vs. 7 days/week) longer. Therefore an additional AF of 8.4 is added to the OEL value of 5 ppm, resulting in a DNEL for general population of 0.60 ppm (4.5 mg/m3).

  • BASF AG (1989) Report: Inhalation toxicity of 2-ethylhexyl acrylate as vapor in rats (3 months study), project-no. 50I081/8502,  
  • Bogdanffy MS, Fame SR (1994), Olfactory mucosal toxicity, Integration of morphological and biochemical data in mechanistic studies; Dubasuc esters as an example. Inhalation Toxicology 6, 205-219
  • Frederick CB, Lomax LG, Black KA, Finch L, Scribner HE, Kimbel JS, Morgan KT, Subramaniam PR, Morris JB (2002) Use of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry comparisons of ester vapors. Toxicol. Appl. Pharmacol., 183, 23-40
  • Mainwaring G, Foster JR, Lund V, Green T (2001) Methyl methacrylate toxicity in rat nasa epithelium: studies of the mechanism of action and comparisons  between species. Toxicology 158, 109-118
  • MAK evaluation 2-ethylhexyl acrylate, Toxikologische arbeitsmedizinische Begründung von MAK-Werten, 42. Lieferung 2007