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The sensitization potential of methyl methacrylate and ethyl methacrylate
Edward
M. Jackson
The Sensitization Potential of Methyl Methacrvlate and Ethyl Methacrylate I
Methyl methacrylate (M&LA) and ethyl methacrylate (EMA) are esters of methacrylic acid in the methacrylate class of chemicals, commonly referred to as plastics (see Table 1). Methacrylates are approved for use in a wide variety of medical devices and cosmetic applications, which are listed in Table 2. Despite this wide use of methacrylates, there is confusion in the legal/regulatory literature. First, methyl methacrylate has been incorrectly reported as being banned’ by the U.S. Food and Drug Administration (FDA). Methyl methacrylate has not been banned by the FDA. In 1974, the FDA won a preliminary injunction against a product known as Long Nails, manufactured by C.E.B. Products, Inc. when injuries caused by that product were reported to the agency. After discussions with experts in dermatology, the FDA concluded that the liquid methyl methacrylate in Long Nails was “poisonous and deleterious.” The FDA seized several lots of the Long Nails product. This resulted in several other products containing methyl methacrylate to be voluntarily withdrawn from the market in 1975 and 1976. Second, the U.S. Environmental Protection Agency (EPA) has reviewed ethyl methacrylate to determine an Acceptable Daily Intake (ADI) for the workplace.2 In the absence of sufficient information on ethyl methacrylate, the EPA simply applied the AD1 value for methyl methacrylate. Many construe this as equating the toxicological potency of ethyl methacrylate with methyl methacrylate, which is patently inappropriate. Third, the U.S. National Institute of Occupational Safety and Health (NIOSH) issued a report to provide recommendations for nail salon operators workingwith ethyl methacrylate in sculptured nail applications. 3 The NIOSH report con-
From Jackson Research Associates Inc, Sumner, WA. Presented in part at the Ninth Annual Meeting ofthe Amxrican oj-Contact Dermatitis, Orlando, FL, Februa?y X,1998.
Society
Address repint requests to EdwardM.Jackson, PhD, President, Jackson Research Associates Inc, 20203 121st St., Court E, Sumner, WA 98390. CofyKght 0 1999 6y WB. Saunders Company 1046-199x/1002-0012/$10.00/0
American
Journal
of Contact
Dermatitis,
tains opinion and editorializing that is unsupported by the scientific and medical literature, which incorrectly describes ethyl methacrylate as a “potent sensitizer” which “can cause allergic reaction is if the dose is large enough.” Unfortunately, the contact dermatitis literature on methyl methacrylate and ethyl methacrylate mirrors some of the confusion generated by the inaccuracies in the legal/regulatory literature. Of paramount importance for the practicing clinician is to bear in mind that the methacylate class of compounds, commonly referred to as plastics, is not the same as either the yanoacylates (such as Krazy Glue), nor the acylates. With this understanding of methacrylates, some sense can be made of the information on methyl methacrylate and ethyl methacrylate in the contact dermatitis literature. Methyl methacrylate has been the subject of an expert review by the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC).” Ethyl methacrylate, on the other hand, has been reviewed by the Expert Panel of the Cosmetic Ingredient Review.’ This 1994 review published in 1995 has been recently updated.5 Table 3 is a summary of the cutaneous effects reported in lp4,j It should be noted that these expert reports. any positive report was used to record a positive cutaneous effect from exposure to either ,MMA or EMA. A critical reading of the contact dermatitis literature, therefore, was not employed. As an example, if case reports of sensitization by MMA or EMA were critically reviewed and weighted the result for MMA would have been +++, whereas the case reports for EMA would have been +. The reason for this is that the expert reports could only identify four cases, for a total of six patients reported as positive to EMA. There are many more case reports of patients reported as positive to MMA. In conclusion, both MMA and EMA have the potential to cross-react with other methacrylates in sensitized individuals. MMA can produce irritant contact dermatitis, and is a sensitizer; EMA, Vol 10, No 1 (March),
1999:pp
49-50
49
50
Edward
Table 1. Methacrylates
M. Jackson
Table 2. Methacrylates
Methyl methacrylate Ethyl methacrylate N-butyl methacrylate I-butyl methacrylate Lauryl methacrylate 2-hydroxyethyl methacrylate N-propyl methacrylate I-propyl methacrylate T-butyl methacrylate Cyclohexyl methacrylate Phenyl methacrylate Benzyl methacrylate Stearyl methacrylate Isobornyl methacrylate Ethylene glycol dimethacrylate Diethyleneglycol dimethacrylate 1,6-hexanediol dimethacrylate Ethylene glycol methyl ether methacrylate Ethylene glycol phenyl ether methacrylate 2-(methylthio)ethyl methacrylate Hydroxypropyl methacrylate Trimethylsilyl methacrylate 1,3-butanediol dimethacrylate 1,4-butanediol dimethacrylate Diethyleneglycol methyl ether methacrylate
Medical
Devices
Cosmetics Sculptured
Table 3. Comparison
of the Cutaneous
Irritant contact dermatitis Allergic contact dermatitis Prognostic patch testing Diagnostic patch testing Case reports Occupational exposure Medical personnel Patients Nail salon technicians Nail salon clients Cross sensitization
References on
2. U.S. Environmental Protection Agency: Healthy and environmental profile for ethyl methacrylate. Report EPA/600/X-86/ DC, June,
1986
Effects
of MMA
MMA
3. Spencer
AB,
Estill
CF,
McCammon
DC, April
1995 5. Jackson
EM: Expert
EM4
+
-
+ + + + -
-
+ -
+ + -
+
+
JB,
chemical hazards in the nail salon industry. for Occupational Safety and Health Report Washington,
Review Expert Panel: Final Report Co1 Tax 14(5):452-467, 1995
nails
and EMA1,4,5
et al: Controlling National No. ECTB
Institute 17 l-05v,
22,1997
4. Joint assessment of commodity Methacrylate CAS No. 80-62-6,
1. The Cosmetic Ingredient Ethyl Methacrylate. JAm
Devices
Hearing aids Contact lenses Dental plates Dental fillings Prostheses Bone cement
on the other hand, has not been shown to cause irritant conact dermatitis, and is a weak sensitizer.
212. Washington,
in Medical
and Cosmetics
chemicals no. 30, Methyl Brussels, Belgium, February,
toxicological/pharmacological
opinion
ethyl methacrylate (EMA). Prepared for the American Association October 30, 1998, presented to the Expert the Cosmetic 3,1998
Ingredient
Review
(Washington,
on
Beauty Panel of
DC) December
M. Jackson
The Sensitization Potential of Methyl Methacrvlate and Ethyl Methacrylate I
Methyl methacrylate (M&LA) and ethyl methacrylate (EMA) are esters of methacrylic acid in the methacrylate class of chemicals, commonly referred to as plastics (see Table 1). Methacrylates are approved for use in a wide variety of medical devices and cosmetic applications, which are listed in Table 2. Despite this wide use of methacrylates, there is confusion in the legal/regulatory literature. First, methyl methacrylate has been incorrectly reported as being banned’ by the U.S. Food and Drug Administration (FDA). Methyl methacrylate has not been banned by the FDA. In 1974, the FDA won a preliminary injunction against a product known as Long Nails, manufactured by C.E.B. Products, Inc. when injuries caused by that product were reported to the agency. After discussions with experts in dermatology, the FDA concluded that the liquid methyl methacrylate in Long Nails was “poisonous and deleterious.” The FDA seized several lots of the Long Nails product. This resulted in several other products containing methyl methacrylate to be voluntarily withdrawn from the market in 1975 and 1976. Second, the U.S. Environmental Protection Agency (EPA) has reviewed ethyl methacrylate to determine an Acceptable Daily Intake (ADI) for the workplace.2 In the absence of sufficient information on ethyl methacrylate, the EPA simply applied the AD1 value for methyl methacrylate. Many construe this as equating the toxicological potency of ethyl methacrylate with methyl methacrylate, which is patently inappropriate. Third, the U.S. National Institute of Occupational Safety and Health (NIOSH) issued a report to provide recommendations for nail salon operators workingwith ethyl methacrylate in sculptured nail applications. 3 The NIOSH report con-
From Jackson Research Associates Inc, Sumner, WA. Presented in part at the Ninth Annual Meeting ofthe Amxrican oj-Contact Dermatitis, Orlando, FL, Februa?y X,1998.
Society
Address repint requests to EdwardM.Jackson, PhD, President, Jackson Research Associates Inc, 20203 121st St., Court E, Sumner, WA 98390. CofyKght 0 1999 6y WB. Saunders Company 1046-199x/1002-0012/$10.00/0
American
Journal
of Contact
Dermatitis,
tains opinion and editorializing that is unsupported by the scientific and medical literature, which incorrectly describes ethyl methacrylate as a “potent sensitizer” which “can cause allergic reaction is if the dose is large enough.” Unfortunately, the contact dermatitis literature on methyl methacrylate and ethyl methacrylate mirrors some of the confusion generated by the inaccuracies in the legal/regulatory literature. Of paramount importance for the practicing clinician is to bear in mind that the methacylate class of compounds, commonly referred to as plastics, is not the same as either the yanoacylates (such as Krazy Glue), nor the acylates. With this understanding of methacrylates, some sense can be made of the information on methyl methacrylate and ethyl methacrylate in the contact dermatitis literature. Methyl methacrylate has been the subject of an expert review by the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC).” Ethyl methacrylate, on the other hand, has been reviewed by the Expert Panel of the Cosmetic Ingredient Review.’ This 1994 review published in 1995 has been recently updated.5 Table 3 is a summary of the cutaneous effects reported in lp4,j It should be noted that these expert reports. any positive report was used to record a positive cutaneous effect from exposure to either ,MMA or EMA. A critical reading of the contact dermatitis literature, therefore, was not employed. As an example, if case reports of sensitization by MMA or EMA were critically reviewed and weighted the result for MMA would have been +++, whereas the case reports for EMA would have been +. The reason for this is that the expert reports could only identify four cases, for a total of six patients reported as positive to EMA. There are many more case reports of patients reported as positive to MMA. In conclusion, both MMA and EMA have the potential to cross-react with other methacrylates in sensitized individuals. MMA can produce irritant contact dermatitis, and is a sensitizer; EMA, Vol 10, No 1 (March),
1999:pp
49-50
49
50
Edward
Table 1. Methacrylates
M. Jackson
Table 2. Methacrylates
Methyl methacrylate Ethyl methacrylate N-butyl methacrylate I-butyl methacrylate Lauryl methacrylate 2-hydroxyethyl methacrylate N-propyl methacrylate I-propyl methacrylate T-butyl methacrylate Cyclohexyl methacrylate Phenyl methacrylate Benzyl methacrylate Stearyl methacrylate Isobornyl methacrylate Ethylene glycol dimethacrylate Diethyleneglycol dimethacrylate 1,6-hexanediol dimethacrylate Ethylene glycol methyl ether methacrylate Ethylene glycol phenyl ether methacrylate 2-(methylthio)ethyl methacrylate Hydroxypropyl methacrylate Trimethylsilyl methacrylate 1,3-butanediol dimethacrylate 1,4-butanediol dimethacrylate Diethyleneglycol methyl ether methacrylate
Medical
Devices
Cosmetics Sculptured
Table 3. Comparison
of the Cutaneous
Irritant contact dermatitis Allergic contact dermatitis Prognostic patch testing Diagnostic patch testing Case reports Occupational exposure Medical personnel Patients Nail salon technicians Nail salon clients Cross sensitization
References on
2. U.S. Environmental Protection Agency: Healthy and environmental profile for ethyl methacrylate. Report EPA/600/X-86/ DC, June,
1986
Effects
of MMA
MMA
3. Spencer
AB,
Estill
CF,
McCammon
DC, April
1995 5. Jackson
EM: Expert
EM4
+
-
+ + + + -
-
+ -
+ + -
+
+
JB,
chemical hazards in the nail salon industry. for Occupational Safety and Health Report Washington,
Review Expert Panel: Final Report Co1 Tax 14(5):452-467, 1995
nails
and EMA1,4,5
et al: Controlling National No. ECTB
Institute 17 l-05v,
22,1997
4. Joint assessment of commodity Methacrylate CAS No. 80-62-6,
1. The Cosmetic Ingredient Ethyl Methacrylate. JAm
Devices
Hearing aids Contact lenses Dental plates Dental fillings Prostheses Bone cement
on the other hand, has not been shown to cause irritant conact dermatitis, and is a weak sensitizer.
212. Washington,
in Medical
and Cosmetics
chemicals no. 30, Methyl Brussels, Belgium, February,
toxicological/pharmacological
opinion
ethyl methacrylate (EMA). Prepared for the American Association October 30, 1998, presented to the Expert the Cosmetic 3,1998
Ingredient
Review
(Washington,
on
Beauty Panel of
DC) December