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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29.6 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
11.9
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
88 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
4
Acute/short term exposure
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.25 mg/kg bw/day
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
82.8
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

Long term exposure
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Value:
1 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Dose descriptor starting point:
other: NOAEL

Workers - Hazard for the eyes

Additional information - workers

MAA is corrosive and at lower concentrations irritating to tissue. The DNELs derived for oral/dermal and inhalation for long-term exposure are considered sufficiently protective of acute exposure.

Acute, short-term and long-term exposure - local effects:

Undiluted MAA induces full-depth destruction of the skin after 3 min contact. It is considered to be highly corrosive to tissues.

Dilutions if MAA in acetone and water show mild irritation at 4.8 % in a study in mice, in which dilutions of MAA were applied for 21 d in succession, while the effects are more pronounced at 9.6 % in acetone and progress to severe irritation at 19.2 % in acetone (see repeated dose section). There was no effect after single exposures to 5 % in mice and only minimal effects after repeated exposure over 3 weeks. The 1 % DNEL provides a sufficient margin of safety.

Long-term exposure (inhalation) - local effects

In an OECD 413 guideline study (subchronic inhalation toxicity: 90-day) 10 male and female Sprague Dawley rats per test group were whole body exposed to a vapour of the test substance on 6 hours per working day for 90 days (65 exposures). The target concentrations were 20, 40, 100 and 350 ppm (corresponding to 70, 141, 352 and 1232 mg/m3). A concurrent control group was exposed to conditioned air. Methacrylic acid induced signs of general toxicity as indicated by decreased body weight, body weight gain, food consumption and transiently food efficiency in the high concentration male animals. At a concentration as high as 350 ppm, the local irritating effect was marginal, indicated by the hypertrophy/hyperplasia of the respiratory epithelium in the nasal cavity of two female animals. Substance-related changes of the sexual organs were not noted in any of the exposed animals, nor were there any changes of sperm mobility and sperm head counts. Under the current test conditions, the no-observed adverse effect level (NOAEL) in this study is 100 ppm for the male and female rats.

For inhaled acids there is no reason to suspect that there is increased sensitivity in the local irritant effects from subchronic to chronic exposure (ECETOC, 2010). Therefore, the absence of irritation at 100 ppm is used as the point of departure (POD) for the derivation of the DNEL for local effects.

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

352 mg/m3(100 ppm)

NOAEC for local effects in subchronic inhalation study

Step 2) Modification of starting point

8/6


 

-

- Correction of exposure duration in study (6 hrs/day) to default worker exposure (8 hrs/day) is required.

-Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3) is not required (ECHA 2008)because it is a local, concentration-driven effect.

Step 3) Assessment factors

 

 

Interspecies

1

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

Intraspecies

3

Default AF (ECETOC, 2010)

Exposure duration

1

The NOAEC is based on a 13-week study. AF for extrapolation fromSub-chronic to chronic(ECETOC, 2010).

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 on NOAEC for local effects in subchronic inhalation study of 352 mg/m3(100 ppm)

Using a total factor (POD modifier and AF) of 4 (8/6 x 1 x 3 x 1) a DNELlong-term,workerof 88 mg/m3(25 ppm) is derived.

 

 

Long-term exposure (dermal) - systemic effects

For chronic, dermal systemic effects there are no relevant studies. Therefore the point of departure (POD) is derived by reading across from the same study which has already been described above – the 90 d inhalation study with MAA.

  

Description

Value

Remark

Step 1) Relevant dose-descriptor

352 mg/m3(100 ppm)

NOAEC for systemic effects in subchronic inhalation study in rats, 5 d/wk, 6 h/d

Step 2) Modification of starting point

1

0.29 m³/kg

Route-to-route extrapolation

Correction for rat standard breathing volume for 6h (ECHA R8 guidance p. 26, ECHA 2010)

Step 3) Assessment factors

 

 

Interspecies

4

- allometric scaling factor extrapolating from rat to human

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 2008).

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 on a NOAEC of 352 mg/m3(100 ppm) for systemic effects in subchronic inhalation study in rats.

Using a total factor (POD modifier and AF) of 82.8 (1/0.29 x 4 x 3 x 2) a DNELlong-term,workerof 4.25 mg/kg/d is derived.

Long-term exposure (inhalation) - systemic effects

For chronic systemic effects the key study is the same that has been described above for local effects – the 90 d inhalation study with MAA:

In regard to chronic toxicity by inhalation the most sensitive endpoint is local irritation in the upper respiratory tract. The only systemic effect at this concentration is reduced body weight gain and this is associated with reduced food consumption rather than true systemic toxicity. For inhaled acids there is no reason to suspect that there is increased sensitivity in the local irritant effects from subchronic to chronic exposure (ECETOC, 2010). As there were no indications of specific target organ toxicity in the 90 day inhalation study with MAA and acute, subacute and chronic studies with the methyl ester (hydrolysed on a molar basis to MAA) show no specific target organ toxicity in the same dose range, read-across to the chronic MMA data are sufficient to satisfy the endpoint.

With methyl methacrylate, the US National Toxicology Program conducted a series of repeat-exposure inhalation toxicity studies of increasing duration in male and female rats and mice. Effects on the nasal respiratory tract were seen in studies in rats and mice in studies of 14 weeks [Battelle Pacific Northwest Lab (1980a) and 104 weeks duration (NTP; 1986a). In the 14 week study 10 male and female rats and mice were exposed to MMA concentrations 0, 500, 1000, 2000, 3000 and 5000 ppm (6 hr/day, 5 days/wk for 97 d). In the 2 year study for 6 hr/day, 5 days/wk for 24 months 50 male and female rats and mice were treated with 2 concentrations of MMA: rats, male 500 and 1000 ppm; female 250 and 500 ppm; mice male and female, 500 and 1000 ppm.

As the no-observed adverse effect level (NOAEL) in the subchronic study on MAA (100 ppm) is below the NOAEL for other systemic effects in the chronic study with MMA it is protective for systemic toxicity and therefore can be used as the basis for the chronic NOAEC, which is used as the point of departure (POD) for the derivation of the DNEL for chronic, systemic effects.

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

352 mg/m3(100 ppm)

NOAEC for systemic effects in subchronic inhalation study in rats, 5 d/wk, 6 h/d

Step 2) Modification of starting point

8/6


 

10 m3/6.7 m3

- Correction of exposure duration in study (6 hrs/day) to default worker exposure (8 hrs/day) is required.

-Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3) is required (ECHA 2008).

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling rat to humans as inhalation (ECHA 2008). 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 2008).

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 on a NOAEC of 352 mg/m3(100 ppm) for systemic effects in subchronic inhalation study in rats.

Using a total factor (POD modifier and AF) of 11.9 a DNELlong-term,workerof 29.6 mg/m3 (8.4 ppm) is derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.3 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
56
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.55 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
53.7
Dose descriptor:
NOAEC
Acute/short term exposure
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.55 mg/kg bw/day
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
138
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
1

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

MAA is corrosive and at lower concentrations irritating to tissue. The DNELs derived for oral/dermal and inhalation for long-term exposure are considered sufficiently protective of acute exposure.The details of the calculations with the consumer-specific assessment factors are detailed in the tables below. The descriptions of the study details are not repeated here and may be obtained from the worker part.

Acute, short-term and long-term exposure - local effects:

Undiluted MAA induces full-depth destruction of the skin after 3 min contact. It is considered to be highly corrosive to tissues.

Dilutions if MAA in acetone and water show mild irritation at 4.8 % in a study in mice, in which dilutions of MAA were applied for 21 d in succession, while the effects are more pronounced at 9.6 % in acetone and progress to severe irritation at 19.2 % in acetone (see repeated dose section). There was no effect after single exposures to 5 % in mice and only minimal effects after repeated exposure over 3 weeks. It is generally accepted that mice are more sensitive than rabbits or humans . Therefore, the 1 % DNEL provides a sufficient margin of safety.

Long-term exposure (inhalation) - local effects

As in the case of workers, the absence of irritation at 100 ppm is used as the point of departure (POD) for the derivation of the DNEL for local effects for the general public.

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

352 mg/m3(100 ppm)

NOAEC for local effects in subchronic inhalation study

Step 2) Modification of starting point

24/6

7/5

-

- Correction of exposure duration in study (6 hrs/day) to default general population exposure (8 hrs/7day and 7day/wk) is required

-Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/6.7 m3) is not required (ECHA 2008)because it is a local, concentration-driven effect.

Step 3) Assessment factors

 

 

Interspecies

1

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

Intraspecies

5

Default AF (ECETOC, 2010)

Exposure duration

1

The NOAEC is based on a 13-week study. AF for extrapolation fromSub-chronic to chronic(ECETOC, 2010).

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 on NOAEC for local effects in subchronic inhalation study of 352 mg/m3(100 ppm)

Using a total factor (POD modifier and AF) of 28 (24/6 x 7/5 x1 x 5 x 1) a DNELlong-term,general_publicof 12.6 mg/m3 (3.57 ppm) is derived.

 

 

Long-term exposure (dermal) - systemic effects

For chronic, dermal systemic effects there are no relevant studies. Therefore the point of departure (POD) is derived by reading across from the same study which has already been described above – the 90 d inhalation study with MAA.

 

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

352 mg/m3(100 ppm)

NOAEC for systemic effects in subchronic inhalation study in rats, 5 d/wk, 6 h/d

Step 2) Modification of starting point

1

0.29 m³/kg

Route-to-route extrapolation

Correction for rat standard breathing volume for 6h (ECHA R8 guidance p. 26, ECHA 2010)

Step 3) Assessment factors

 

 

Interspecies

4

- allometric scaling factor extrapolating from rat to human

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 2008).

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 on a NOAEC of 352 mg/m3(100 ppm) for systemic effects in subchronic inhalation study in rats.

Using a total factor (POD modifier and AF) of 82.8 (1/0.29 x 4 x 3 x 2) a DNELlong-term,general_populationof 4.25 mg/kg/d is derived.

Long-term exposure (inhalation) - systemic effects

For chronic systemic effects the key study is the same that has been described above for local effects – the 90 d inhalation study with MAA. As the no-observed adverse effect level (NOAEL) in the subchronic study on MAA (100 ppm) is below the NOAEL for other systemic effects in the chronic study with MMA it is protective for systemic toxicity and therefore can be used as the basis for the chronic NOAEC, which is used as the point of departure (POD) for the derivation of the DNEL for chronic, systemic effects.

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

352 mg/m3(100 ppm)

NOAEC for systemic effects in subchronic inhalation study

Step 2) Modification of starting point

24/6

 

 

7/5

Correction of exposure duration in rats (6 hrs/day) to default general population exposure (24 hrs/day) is required.

Correction for experimental exposure of 5 days to 7 days for general population

Step 3) Assessment factors

 

 

Interspecies

1

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

Intraspecies

5

Default AF for General Population (ECHA 2008)

Exposure duration

2

The NOAEC is based on a 13-week study. AF for extrapolation from Sub-chronic to chronic (ECETOC, 2010).

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 on a NOAEC 352 mg/m3(100 ppm) for systemic effects in a subchronic inhalation study

Using a total factor (POD modifier and AF) of 56 (26 / 6 x 7 / 5 x 5 x 2) a DNELlong-term,general_population of 6.3 mg/m3(1.8 ppm) is derived.