Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.

Workers - 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:
DNEL (Derived No Effect Level)
Value:
1 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
1

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Acrylic acid is an important intermediate for polymer industry and is produced in large quantities within the European Union.

Acrylic acid serves as an industrial intermediate product, i .e . it is either processed directly into a polyacrylate or polymerised via the intermediate stage of an acrylate ester. Furthermore, acrylic acid is used as an ingredient and occurs as residual monomer in consumer products like adhesives, paints, binding agents and printing inks.

DNEL derivation:

In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m3), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.

The most critical effect of acrylic acid is its strong irritation property, it causes severe burns to skin and eyes in animals and severe irritation in the

respiratory tract. The corrosive properties of the substance are demonstrated in a dose dependent manner . In humans acrylic acid causes skin corrosion and irritation of the respiratory tract.

Within the MAK documentation following considerations to evaluate the OEL for acrylic acid were made:

In a 90-day study, a NOAEC of 25 ppm was obtained for rats after 6-hour inhalation per day, whereas slight damage to the olfactory epithelium was observed in mice even at 5 ppm.

Investigations with an anatomical model of the nasal cavity of an adult rat showed that only 7 %–10 % of the airflow inhaled passes over the olfactory epithelium (Keyhani et al. 1995). Similar investigations with a rat nose model showed that between 13.2 %and 21.7 % of the inspiratory airflow reaches the affected olfactory epithelium in the dorsal medial meatus, depending on the flow rate and the direction of the nostrils (upwards or downwards). At the normal inspiratory rate of 288 ml/min for the F344 rat examined, the rates were 14.6 % if the nostrils pointed downwards and 17 % if they pointed upwards (Kimbell et al. 1997).

After an acrylic acid concentration of 131 ppm was drawn through the upper respiratory passages of tracheotomized F344 rats at a flow rate of 200 ml/min, 97 % of the substance was found to be deposited in the respiratory tract (Morris and Frederick 1995).

The local tissue dose of inhaled acrylic acid in the nasal cavity of humans and rats was estimated by means of a CFD-PBPK model (computational fluid dynamics and physiologically based pharmacokinetic dosimetry model) by way of comparison. Steady-state simulations of the anterior nasal cavity of rats and the human nasal cavity were carried out in a 3-dimensional model. The release of acrylic acid vapour onto the mucous membranes of the upper respiratory tract was determined region for region in the simulations. Calculations were carried out with respiratory minute volumes of 0.1, 0.3 and 0.5 l/minute for rats and 11.4 and 18.9 l/minute for humans. Two compartments with olfactory epithelia (dorsal meatus and ethmoid region) were included for rats while only one compartment was included for the human model since humans have no ethmoid. The model included  the effect of the buffer capacity of the mucus on the degree of ionization of the acid and the diffusion of the ionized and non-ionized species. The model also incorporated local physicochemical processes, partition coefficients, the metabolism of acrylic acid, flow conditions and respiratory parameters. Deposition of 50 % was calculated for the human nasal cavity using this model; compared with the 97 % measured in rats (Morris and Frederick 1995) this is plausible in view of the somewhat wider respiratory passages of the human nose (Fredericket al. 1998). The amounts deposited of a number of substances were also well predicted for rats (Frederick et al. 2001). In further calculations using this model, similar effects on the olfactory epithelium were estimated after acrylic acid concentrations of 4.4 and 25 ppm for rats (respiratory minute volume 0.250 l/minute) and humans (respiratory minute volume 13.9 l/minute) (Andersen et al. 2000; Frederick et al. 2001). However, since the values of important model parameters (e.g. gas phase diffusivity, diffusivity in mucus, diffusivity in squamous epithelium, tissue diffusivity and blood flow through the nasal epithelium) are not based on measurements, but on model simulations and assumptions, the conclusions drawn from the model are to not absolutely reliable.Assuming uniform distribution over the surface of the nasal cavity the ratio for the amounts of acrylic acid deposited in the olfactory epithelium of rats and humans per time unit is about 1 to 3. Taking into account the different airflow that passes over the olfactory epithelium of both species, the effect on the olfactory epithelium is about 1 to 1.6 (Table 1). This calculation considers the respiratory minute volume increased under workplace conditions as the worst-case assumption. In view of the logPowof 0.46 (EU 2002) for acrylic acid, it must be assumed, however, that a larger fraction is deposited in the anterior region of the nose than in the posterior region. Since the olfactory epithelium of the rat is located in the posterior region of the nasal cavity and accounts for almost 50 % of the surface area ofthe nasal cavity (in humans only 4 %; Frederick et al. 1998), i.e. most of the olfactory epithelium is closer to the portal of entry in rats, more acrylic acid will reach the olfactory epithelium in rats than in humans. It can therefore be assumed that the concentrations to which the olfactory epithelium is exposed are not higher in humans than in rats.

Table 1.Comparison of the exposure level of the olfactory epithelium in rats and humans; exposure to acrylic acid concentrations of 25 ppm (75 µg/l)

 

Rat

Human

respiratory minute volume

0.175 l/min for 250 g rat (EPA 1988)

10 m3/8 h= 20.8 l/min

inhaled acrylic acid amount/min

13.1 µg

1563 µg

surface of the nasal cavity

13.79 cm2(Fredericket al. 1998)

245.9 cm2(Fredericket al. 1998)

surface of the olfactory epithelium

6.72 cm2(Fredericket al. 1998)

13.2 cm2(Fredericket al. 1998)

deposition in the nasal cavity

97 % (Morris and Frederick 1995)

about 50 % (Fredericket al. 1998)

average dose on the nasal surface (assuming uniform distribution in the nose)

13.1 µg/min/13.79 cm2× 0.97
= 0.92 µg/cm2/min

1563 µg/min/245.9 cm2× 0.5
= 3.18 µg/cm2/min

airflow over the olfactory epithelium

about 15 % (Fredericket al. 1998)

about 7 % (Fredericket al. 1998)

ratio of the exposure of the olfactory epithelium taking into account the different airflow over the olfactory epithelium (rat = 1)

1

3.18/0.92 × 7 %/15 % = 1.6

Within the MAK documentation it was estimated that the exposure level of the olfactory epithelium in humans at an increased respiratory minute volume (about 21 l/minute = 10 m3/8 hours) is not higher than that in rats (resting tidal volume) and is lower than that in mice. Since irritation of the olfactory epithelium does not substantially increase with time and since interindividual differences are probably slight as acrylic acid does not have to be metabolized, the MAK value for acrylic acid has been established at 10 ppm. Because irritation is the critical effect, acrylic acid has been classified by MAK in Peak limitation category I, and since there are no studies to establish an excursion factor, a basic excursion factor of 1 has been fixed.

  • Andersen M, Sarangapani R, Gentry R, Clewell H, Covington T, Frederick CB (2000) Application of a hybrid CFD-PBPK nasal dosimetry model in an inhalation risk assessment: an example with acrylic acid.Toxicol Sci 57: 312–325
  • Frederick CB, Bush ML, Lomax LG, Black KA, Finch L, Kimbell JS, Morgan KT, Subramaniam RP, Morris JB, Ultman JS (1998) Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways.Toxicol Appl Pharmacol 152: 211–231
  • Frederick CB, Gentry PR, Bush ML, Lomax LG, Black KA, Finch L, Kimbell JS, Morgan KT, Subramaniam RP, Morris JB, Ultman JS (2001) A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities following inhalation exposure.Inhal Toxicol 13: 359–376
  • Keyhani K, Scherer PW, Mozell MM (1995) Numerical simulation of airflow in the human nasal cavity.J Biomech Eng 117: 429–441
  • Kimbell JS,, Gross EA,,RB, Morgan KT (1997) Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages.Toxicol Appl Pharmacol 145: 388–398
  • Morris JB, Frederick CB (1995) Upper respiratory tract uptake of acrylate esters and acid vapors.Inhal Toxicol 7: 557–574

The short term exposure - local effect dermal DNEL is based on 2 studies in mice. A short term (2 weeks) irritation study (BAMM 1979) as well as on a 13 week dermal study (IATG 1979) .

The 13-week dermal irritation study was conducted in three strains of mice to assess the degree and time course of irritation produced by application of acrylic acid three times a week to the dorsal thoracic area (dorsal mid-line midway between the caudal margin of the scapulae and the last rib; approx. 1 cm2) of mice at levels of 0, 1 and 4 percent in acetone. Each dose level consisted of 30 female ICR, 30 male C3H and 30 female B6C3F1 mice. Comparable skin irritation to ICR, C3H and B6C3F1 mice at the 4% dose level are described. Minimal skin reactions were observed in all strains at the 1% dose level. Gross lesions other than skin reactions were incidental to treatment. Microscopic findings characterized as proliferative, degenerative or inflammatory changes were seen predominantly at the 4% level in all strains, occasionally at the 1% level and only rarely in controls. Body weights of all strains at all dose levels were similar.

In the 2 week study the repeated application of 10% and 5% acrylic acid in acetone was irritating to the mouse skin whereas 1% acrylic acid in acetone (v/v) was non-irritating to the skin of mice and did not result in death or loss of body weight.

Based on these two studies it was calculated, that short-term exposure of 100 µl 1% acrylic acid in acetone (= 1.04 mg acrylic acid) will not cause a local effect to skin. No additional assessment factor for interspecies as well as intraspecies differences are taken for this irritation of skin, since in the cited studies acrylic acid was applied repeatedly and as already stated in the MAK documentation interindividual differences are probably slight for irritation as acrylic acid does not have to be metabolized. The DNEL short-term local effect is 1 mg/cm2.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/m³
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m³), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.

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:
DNEL (Derived No Effect Level)
Value:
1 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/cm²
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
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Acrylic acid is an important intermediate for polymer industry and is produced in large quantities within the European Union.

Acrylic acid serves as an industrial intermediate product, i .e . it is either processed directly into a polyacrylate or polymerised via the intermediate stage of an acrylate ester . Furthermore, acrylic acid is used as an ingredient and occurs as residual monomer in consumer products like adhesives, paints, binding agents and printing inks.

DNEL derivation:

In 2006 the German MAK commission determined a scientific OEL for acrylic acid of 10 ppm (30 mg/m3), which was confirmed as a German OEL by the regulatory authorities in 2007 and the European Scientific Committee for Occupational Exposure Limits in 2008.

The most critical effect of acrylic acid is its strong irritation property, it causes severe burns to skin and eyes in animals and severe irritation in the

respiratory tract. The corrosive properties of the substance are demonstrated in a dose dependent manner . In humans acrylic acid causes skin corrosion and irritation of the respiratory tract.

Within the MAK documentation following considerations to evaluate the OEL for acrylic acid were made:

In a 90-day study, a NOAEC of 25 ppm was obtained for rats after 6-hour inhalation per day, whereas slight damage to the olfactory epithelium was observed in mice even at 5 ppm.

Investigations with an anatomical model of the nasal cavity of an adult rat showed that only 7 %–10 % of the airflow inhaled passes over the olfactory epithelium (Keyhani et al. 1995). Similar investigations with a rat nose model showed that between 13.2 % and 21.7 % of the inspiratory airflow reaches the affected olfactory epithelium in the dorsal medial meatus, depending on the flow rate and the direction of the nostrils (upwards or downwards). At the normal inspiratory rate of 288 ml/min for the F344 rat examined, the rates were 14.6 % if the nostrils pointed downwards and 17 % if they pointed upwards (Kimbell et al. 1997).

After an acrylic acid concentration of 131 ppm was drawn through the upper respiratory passages of tracheotomized F344 rats at a flow rate of 200 ml/min, 97 % of the substance was found to be deposited in the respiratory tract (Morris and Frederick 1995).

The local tissue dose of inhaled acrylic acid in the nasal cavity of humans and rats was estimated by means of a CFD-PBPK model (computational fluid dynamics and physiologically based pharmacokinetic dosimetry model) by way of comparison. Steady-state simulations of the anterior nasal cavity of rats and the human nasal cavity were carried out in a 3-dimensional model. The release of acrylic acid vapour onto the mucous membranes of the upper respiratory tract was determined region for region in the simulations. Calculations were carried out with respiratory minute volumes of 0.1, 0.3 and 0.5 l/minute for rats and 11.4 and 18.9 l/minute for humans. Two compartments with olfactory epithelia (dorsal meatus and ethmoid region) were included for rats while only one compartment was included for the human model since humans have no ethmoid. The model included  the effect of the buffer capacity of the mucus on the degree of ionization of the acid and the diffusion of the ionized and non-ionized species. The model also incorporated local physicochemical processes, partition coefficients, the metabolism of acrylic acid, flow conditions and respiratory parameters. Deposition of 50 % was calculated for the human nasal cavity using this model; compared with the 97 % measured in rats (Morris and Frederick 1995) this is plausible in view of the somewhat wider respiratory passages of the human nose (Frederick et al. 1998). The amounts deposited of a number of substances were also well predicted for rats (Frederick et al. 2001). In further calculations using this model, similar effects on the olfactory epithelium were estimated after acrylic acid concentrations of 4.4 and 25 ppm for rats (respiratory minute volume 0.250 l/minute) and humans (respiratory minute volume 13.9 l/minute) (Andersen et al. 2000; Frederick et al. 2001). However, since the values of important model parameters (e.g. gas phase diffusivity, diffusivity in mucus, diffusivity in squamous epithelium, tissue diffusivity and blood flow through the nasal epithelium) are not based on measurements, but on model simulations and assumptions, the conclusions drawn from the model are to not absolutely reliable.Assuming uniform distribution over the surface of the nasal cavity the ratio for the amounts of acrylic acid deposited in the olfactory epithelium of rats and humans per time unit is about 1 to 3. Taking into account the different airflow that passes over the olfactory epithelium of both species, the effect on the olfactory epithelium is about 1 to 1.6 (Table 1). This calculation considers the respiratory minute volume increased under workplace conditions as the worst-case assumption. In view of the logPowof 0.46 (EU 2002) for acrylic acid, it must be assumed, however, that a larger fraction is deposited in the anterior region of the nose than in the posterior region. Since the olfactory epithelium of the rat is located in the posterior region of the nasal cavity and accounts for almost 50 % of the surface area ofthe nasal cavity (in humans only 4 %; Frederick et al. 1998), i.e. most of the olfactory epithelium is closer to the portal of entry in rats, more acrylic acid will reach the olfactory epithelium in rats than in humans. It can therefore be assumed that the concentrations to which the olfactory epithelium is exposed are not higher in humans than in rats.

Table 1.Comparison of the exposure level of the olfactory epithelium in rats and humans; exposure to acrylic acid concentrations of 25 ppm (75 µg/l)

 

Rat

Human

respiratory minute volume

0.175 l/min for 250 g rat (EPA 1988)

10 m3/8 h= 20.8 l/min

inhaled acrylic acid amount/min

13.1 µg

1563 µg

surface of the nasal cavity

13.79 cm2(Fredericket al. 1998)

245.9 cm2(Fredericket al. 1998)

surface of the olfactory epithelium

6.72 cm2(Fredericket al. 1998)

13.2 cm2(Fredericket al. 1998)

deposition in the nasal cavity

97 % (Morris and Frederick 1995)

about 50 % (Fredericket al. 1998)

average dose on the nasal surface (assuming uniform distribution in the nose)

13.1 µg/min/13.79 cm2× 0.97
= 0.92 µg/cm2/min

1563 µg/min/245.9 cm2× 0.5
= 3.18 µg/cm2/min

airflow over the olfactory epithelium

about 15 % (Fredericket al. 1998)

about 7 % (Fredericket al. 1998)

ratio of the exposure of the olfactory epithelium taking into account the different airflow over the olfactory epithelium (rat = 1)

1

3.18/0.92 × 7 %/15 % = 1.6

Within the MAK documentation it was estimated that the exposure level of the olfactory epithelium in humans at an increased respiratory minute volume (about 21 l/minute = 10 m3/8 hours) is not higher than that in rats (resting tidal volume) and is lower than that in mice. Since irritation of the olfactory epithelium does not substantially increase with time and since interindividual differences are probably slight as acrylic acid does not have to be metabolized, the MAK value for acrylic acid has been established at 10 ppm. Because irritation is the critical effect, acrylic acid has been classified by MAK in Peak limitation category I, and since there are no studies to establish an excursion factor, a basic excursion factor of 1 has been fixed.

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 10 ppm, resulting in a DNEL for general population of 1.2 ppm ( 3.6 mg/m3).

  • Andersen M, Sarangapani R, Gentry R, Clewell H, Covington T, Frederick CB (2000) Application of a hybrid CFD-PBPK nasal dosimetry model in an inhalation risk assessment: an example with acrylic acid.Toxicol Sci 57: 312–325
  • Frederick CB, Bush ML, Lomax LG, Black KA, Finch L, Kimbell JS, Morgan KT, Subramaniam RP, Morris JB, Ultman JS (1998) Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways.Toxicol Appl Pharmacol 152: 211–231
  • Frederick CB, Gentry PR, Bush ML, Lomax LG, Black KA, Finch L, Kimbell JS, Morgan KT, Subramaniam RP, Morris JB, Ultman JS (2001) A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities following inhalation exposure.Inhal Toxicol 13: 359–376
  • Keyhani K, Scherer PW, Mozell MM (1995) Numerical simulation of airflow in the human nasal cavity.J Biomech Eng 117: 429–441
  • Kimbell JS,, Gross EA,,RB, Morgan KT (1997) Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages.Toxicol Appl Pharmacol 145: 388–398
  • Morris JB, Frederick CB (1995) Upper respiratory tract uptake of acrylate esters and acid vapors.Inhal Toxicol 7: 557–574

The short term exposure - local effect dermal DNEL is based on 2 studies in mice. A short term (2 weeks) irritation study (BAMM 1979) as well as on a 13 week dermal study(IATG 1979).

The 13-week dermal irritation study was conducted in three strains of mice to assess the degree and time course of irritation produced by application of acrylic acid three times a week to the dorsal thoracic area (dorsal mid-line midway between the caudal margin of the scapulae and the last rib; approx.1 cm2) of mice at levels of 0, 1 and 4 percent in acetone. Each dose level consisted of 30 female ICR, 30 male C3H and 30 female B6C3F1 mice. Comparable skin irritation to ICR, C3H and B6C3F1 mice at the 4% dose level are described. Minimal skin reactions were observed in all strains at the 1% dose level. Gross lesions other than skin reactions were incidental to treatment. Microscopic findings characterized as proliferative, degenerative or inflammatory changes were seen predominantly at the 4% level in all strains, occasionally at the 1% level and only rarely in controls. Body weights of all strains at all dose levels were similar.

In the 2 week study the repeated application of 10% and 5% acrylic acid in acetone was irritating to the mouse skin whereas 1% acrylic acid in
acetone (v/v) was non-irritating to the skin of mice and did not result in death or loss of body weight.

Based on these two studies it was calculated, that short-term exposure of 100 µl 1% acrylic acid in acetone (= 1.04 mg acrylic acid) will not cause a local effect to skin.No additional assessment factor for interspecies as well as intraspecies differences are taken for this irritation of skin, since in the cited studies acrylic acid was applied repeatedly and as already stated in the MAK documentation interindividual differences are probaly slight for irritation as acrylic acid does not have to be metabolized. The DNEL short-term local effect is1 mg/cm2.