Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Animal data

There is a great number of reliable studies available to assess the skin sensitising potential of methyl methacrylate. The variety of used test methods is large, providing positive and negative results in almost equal proportions. Nevertheless, in the most common test systems at least one positive test result can be found

 

For a more precise view on the potential for skin sensitisation, a LLNA is an appropriate test system due to the studied dose relationships. Here, Betts et al. (2006) conducted a LLNA comparable to OECD guideline 429 using concentrations from 10 to 100% dissolved in either acetone or acetone/olive oil (4:1 v/v). 25 µL of the preparations were administered daily for three days to four CBA/ca mice per treatment. Five days after the initiation, animals received 3H labelled methyl thymidine five hours before sacrifice. Stimulation indices (SI), based on the 3H-TdR incorporation, were calculated relative to the corresponding vehicle controls and the EC3 values were determined by interpolation. The EC3 value for methyl methacrylate were 60% (w/v) in acetone and 90% (w/v) in acetone/olive oil (4:1); the EC3 value of the 2,4 -Dinitrochlorbenzene as positive control was 0.036%, leading to the assessment that methyl methacrylate has to be considered as weak skin sensitiser.

Human data

Numerous case reports of skin sensitisation exist from certain occupational environments, where frequent and prolonged unprotected skin contact with monomer containing mixtures was common practice. Repeated exposure to undiluted MMA may lead to skin sensitisation in susceptible persons. This was shown, for instance, by Cavelier et al. (1981) as a 48 -hour occlusive patch test with undiluted MMA, containing 1% hydroquinone, caused positive reactions in 3 of 20 volunteers at a challenge 19 days after initial treatment. Forty-five volunteers were patch tested with 20% MMA in olive oil (stabilizer content 1%) and no reactions were observed even after a challenge application after 30 days. The additional influence of the unusually high stabiliser content of 1 % which is a sensitiser in its own right, however, is unclear.

 

Prevalence of MMA Sensitisation: Case Reports and Other Data

Test Group (selection criteria)

Total no. or no. tested

No. tested positive

Incidence (%)

Reference

Potential bias

comments

dental technicians and students (with and without exposure to MMA, no details reported)

175

0

0

Marx et al., 1982

Bias-negative: possibly no history of exposure to MMA

Rem.: small cohort

dental technicians inwho are members of theEmployer'sLiabilityInsuranceAssociationBGFE (~ 95 % of the workforce in that field in)

No. of applications due to recurrent, severe skin disease (BK 5101)

83191

85238

86102

73871

66696

65419

66412

195

206

200

209

214

247

194

0.23

0.24

0.23

0.28

0.32

0.38

0.29

BGFE, 1995

BGFE, 1996

BGFE, 1997

BGFE, 1998

BGFE, 1999

BGFE, 2000

BGFE, 2001

(all: personal communication)

Bias-small

(Two effects balance each other - not everyone is expected to apply (negative bias) but cases with allergies against metals or other chemicals in the field are also included (positive bias))

Rem.: Probably the most reliable estimate

patients with dermatitis with previous contact with (meth)acrylates (dental products, adhesives) ((meth)acrylate allergy suspected, no further details)

82

1

0.8

Guerra et al. (1993)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

* see note below

patients with dermatitis (suspected of (meth)acrylate allergy; no further details)

1161

9

0.8

Schnuch (1997)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

patients with dermatitis (suspected of (meth)acrylate allergy; no further details)

4221

51

1.2

Schnuch (1996)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

patients with dermatitis (suspected of (meth)acrylate allergy; no further details)

4900

3080

4099

5812

 

1.4

1.2

1.6

1.4

Pratt et al. (2004)

Marks et al.(1995, 1998

and 2003)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

patients with dermatitis with previous contact with (meth)acrylate (no further details)

352

17

4.8

Tucker and Beck (1999)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

patients with dermatitis with previous contact with (meth)acrylate (no further details)

271

20

7.4

Kanerva et al. (1997)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

dental technicians with dermatitis, (details re. Exposure to MMA not reported)

72

9

13

Schnuch and Geier (1994)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

1619 patients with contact dermatitis (23 (meth)acrylate-exposed persons were tested, no further details)

23

3

13

Kiec-Swierczynska (1996)

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

dental technicians (with dermatitis, details re. Exposure to MMA not reported)

93

17

16

Peiler et al., 1996

Bias-positive: patients of dermatologists or dermal clinics are a cohort pre-selected for having a problem with the skin

* This reference and all other ones below look at patients, i.e. cohorts which are more or less selective towards the occurrence of dermatitis, all persons without skin problems have no reason to go to a dermatologist and are so inadvertently excluded from the study

 


Migrated from Short description of key information:
Human data
Skin patch test data indicate that MMA is a contact sensitiser in humans.
 
Animal data
Local Lymph Node Assay, mouse: weakly skin sensitising (OECD 429; Betts et al. 2006).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Adoption from the EU risk assessment (2002):

"A small number of case studies have attempted to link MMA exposure with occupational asthma. Authors reported only immediate responses which are most likely due to an airways irritation. While an immunological mechanism may be deduced in a few cases, the majority of cases do not seem to indicate a mechanism resulting in respiratory sensitisation but due to irritative reactions. It was concluded that there is no convincing evidence that methyl methacrylate is a respiratory sensitiser in humans. Thus, a labelling for respiratory sensitisation is not warranted, however, possible non-specific asthmatic responses due to respiratory tract irritation cannot be excluded and labelling with R 37 is sufficient for the protection of humans. ". Under CLP/EU/UN-GHS R37 is equivalent to STOT single exposure Cat. 3.

Justification for classification or non-classification

Based on the various studies on methyl methacrylate, it is considered that the substance comprises the potential for skin sensitisation and has therefore to be classified with R43/ skin sens. Cat. 1 according to 67/548/EEC and UN GHS requirements, respectively.

Based on the available data there is no convincing evidence that MMA causes respiratory sensitisation. Therefore, a classification for respiratory sensitisation is considered as not justified.