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METHYL METHACRYLATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Methyl methacrylate is a flammable, clear, colorless liquid and is a polymerization hazard when exposed to light, heat, oxygen, or ionizing radiation.

Specific Substances

    1) 2-methylpropenoic acid, methyl ester
    2) Methacrylic acid, methyl ester
    3) Alpha-methylacrylic acid
    4) MMA
    5) CAS 80-62-6
    6) "MONOCITE" METHYACRYLATE MONOMER
    7) 50N
    8) METHACRYLATE MONOMER
    9) METHYL ESTER OF METHACRYLIC ACID
    10) MMA (METHYL METHACRYLATE)
    11) MME (METHYL METHACRYLATE)
    12) ST 1
    1.2.1) MOLECULAR FORMULA
    1) C5-H8-O2

Available Forms Sources

    A) FORMS
    1) It is a flammable, clear, colorless liquid; its odor has been described as distinctive, fruity, ester-like, acrid, and pungent. Methyl methacrylate monomer is a polymerization hazard when exposed to light, heat, oxygen, or ionizing radiation. It is usually found as a commercial or technical grade (99.8% pure) which contains inhibitors to prevent polymerization (AAR, 1998; ACGIH, 1999; (Ashford, 1994; Clayton & Clayton, 1994; ILO, 1998; Lewis, 1996; Lewis, 1997; Lewis, 1997; Verschueren, 1983).
    B) SOURCES
    1) Methyl methacrylate may be produced by alcoholysis (methanol + methacrylamide), by esterification (methanol + methacrylic acid), by the combination of acetone cyanohydrin, methanol, and dilute sulfuric acid, and by the oxidation of tert-butyl alcohol to methacrolein and then to methacrlic acid followed by reaction with methanol (Ashford, 1994; Clayton & Clayton, 1994; Lewis, 1997).
    C) USES
    1) Methyl methacrylate is used in the production of acrylics, clear plastics, marble-like surfaces (for kitchens and baths), extrusion powders, paints and inks, adhesive cements, industrial flooring compositions, precast concrete composites, resin mortars, polishes, dental fillers and cements, and surgical implants (ACGIH, 1999; (Woolf & Shaw, 1998; Gesell & Stephen, 1997; Ashford, 1994; Clayton & Clayton, 1994; Hathaway et al, 1996; Lewis, 1997; Raffle et al, 1994).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Methyl methacrylate is used in the production of acrylics, clear plastics, marble-like surfaces, extrusion powders, paints and inks, adhesive cements, industrial flooring compositions, precast concrete composites, resin mortars, polishes, dental fillers, surgical implants, and bone cements.
    B) TOXICOLOGY: Methyl methacrylate decreases the amplitude of the action potential in peripheral nerves by causing lysis of membrane lipids and destruction of the myelin sheath. It is an irritant and sensitizer, and can cause bronchospasm and dermatitis. At high concentrations, it has CNS and respiratory depressant effects. It is thought to promote granuloma formation and trigger focal bone resorption.
    C) EPIDEMIOLOGY: Exposure to liquid methyl methacrylate is generally occupational. It is usually found as a commercial or technical grade (99.8% pure) which contains inhibitors such as hydroquinone or monomethyl ether of hydroquinone to prevent polymerization. Once polymerized, it is inert.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY
    a) ORAL: Significant systemic toxicity is not expected after acute ingestion. If an object made from the polymer is ingested, it presents a potential foreign body (choking) hazard.
    b) DERMAL: Irritation dermatitis, allergic contact dermatitis, numbness, paresthesias, cold sensation in extremities, and cutaneous burns may occur. Eczematous reactions of onychial and paronychial tissues have been reported in patients using acrylic plastic nails. Dystrophic nail changes may persist for months. Irreversible loss of the fingernails has occurred.
    c) INHALATION: Occupational exposure through inhalation has resulted in asthma, narcosis, headache, dizziness, extremity pain, fatigue, sleep disturbances, irritability, memory loss, depression, laryngitis, anorexia, nausea, drowsiness, and decrement in olfactory ability.
    d) OCULAR: Corneal irritation and lens opacity may occur.
    2) SEVERE TOXICITY
    a) INHALATION: Can cause drowsiness, CNS or respiratory depression.
    b) DERMAL: Chronic exposure can cause peripheral neuropathy.
    c) OTHER: Systemic vasodilation and transient hypotension have been reported following use as a bone cement in total hip replacement procedures. Methacrylic acid-containing primers used in artificial nail cosmetic products are highly corrosive and have been associated with respiratory toxicity and cutaneous burn. Refer to "ACIDS" management for information on methacrylic acid.
    0.2.20) REPRODUCTIVE
    A) There is no evidence of methyl methacrylate-induced teratogenicity in humans but there are conflicting reports in animals.
    0.2.21) CARCINOGENICITY
    A) Long-term follow-up of workers does not support the carcinogenicity of methylmethacrylate but chronic exposure in animals has been associated with fibrosarcomas (Anon, 1994; HSDB , 2000).
    B) At the time of this review, no data concerning the carcinogenicity of methyl methacrylate was found in documents by the National Toxicology Program (US DHHS, 1994), NIOSH (Chemsoft(R) , 1996) or in IRIS (IRIS, 1996).
    0.2.22) OTHER
    A) Trace amounts of stabilizers such as hydroquinone or monomethylether of hydroquinone may be added to the methyl methacrylate monomer to prevent spontaneous polymerization (ACGIH, 1986) and are not generally removed. A study conducted to determine the effects of 4 hr exposure of rats to 10 ppm of a hydroquinone failed to find any toxicity related to the stabilizer (Oberly & Tansy, 1985).

Laboratory Monitoring

    A) No specific lab work or diagnostic procedures should be done in the acute setting unless otherwise clinically indicated.
    B) Nerve conduction studies and pulmonary function tests may be conducted to document possible chronic effects of exposure on peripheral nerves and pulmonary effects.
    C) Patch testing may aid in differentiating irritant dermal effects from allergic dermal responses. This information is used to identify sensitized individuals who should be removed from further exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Treat severe hypotension with IV fluids, dopamine, or norepinephrine.
    C) DECONTAMINATION
    1) Significant systemic toxicity is not expected after acute ingestion; gastrointestinal decontamination is generally not warranted. EYES: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persists, an ophthalmologic exam should be performed. DERMAL: Remove contaminated clothing and wash exposed area thoroughly with soap and water. Treat contact dermatitis with topical corticosteroids. INHALATION: Remove from exposure and give supplemental oxygen if necessary. Treat bronchospasm with inhaled beta agonists.
    D) AIRWAY MANAGEMENT
    1) Endotracheal intubation should be performed in patients with excessive drowsiness and the inability to protect their own airway or severe respiratory distress.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) There is no role for hemodialysis.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients who are asymptomatic or have only mild irritation can be managed at home.
    2) OBSERVATION CRITERIA: Patients with deliberate exposure, or more than mild irritation should be referred to a healthcare facility.
    3) ADMISSION CRITERIA: Patients with CNS depression or persistent pulmonary irritation should be admitted.
    4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear. An industrial hygienist and/or occupation medicine specialist may be useful to evaluate workplace exposures.
    H) PITFALLS
    1) Missing an ingestion of another chemical or other possible etiologies for a patient’s symptoms. History of exposure may be difficult to obtain in some settings.
    I) PHARMACOKINETICS
    1) Methyl methacrylate is metabolized to methacrylic acid (via coenzyme A) which is a normal intermediate in the Krebs cycle. It is hydroxylated to a primary alcohol, after which is oxidized to an aldehyde. Finally, it is converted to pyruvic acid. Low quantities of MMA are readily metabolized via the lipolytic pathways. Another pathway of metabolism involves conjugation with glutathione.
    J) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that can cause hypotension (eg, vasodilators, beta blockers, calcium channel blockers), or neurologic disorders. Other chemicals or drugs that cause CNS depression (eg, toxic alcohols, benzodiazepines, opiates/opioids, antipsychotic medications). Diseases or exposures that produce acute respiratory distress (eg, inhalation of acid or alkaline mists, asthma, COPD).
    0.4.3) INHALATION EXPOSURE
    A) DECONTAMINATION
    1) Remove from exposure and give supplemental oxygen if necessary. Treat bronchospasm with inhaled beta agonists.
    B) AIRWAY MANAGEMENT
    1) Endotracheal intubation should be performed in patients with excessive drowsiness and the inability to protect their own airway or severe respiratory distress.
    0.4.4) EYE EXPOSURE
    A) Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persists, an ophthalmologic exam should be performed.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Remove contaminated clothing and wash exposed area thoroughly with soap and water. Treat contact dermatitis with topical corticosteroids.

Range Of Toxicity

    A) TOXICITY: At concentrations of 0.5 to 5 ppm, workers report frequent headaches, pain in the extremities, irritability, loss of memory, excessive fatigue, and sleep disturbances. With air concentrations from 3 to 77 ppm, surgical assistants who mixed methyl methacrylate bone cement in operating rooms described occasional transient eye irritation. TLV-TWA: 50 ppm. NIOSH: TWA: 100 ppm (410 mg/m(3)); IDLH: 1000 ppm; OSHA PEL: 8-hour TWA: 100 ppm (410 mg/m(3)).

Clinical Effects

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) LOSS OF APPETITE
    1) Anorexia and nausea lasting for several hours occurred in dental students working with MMA (Tansy et al, 1974).
    B) INFLAMMATORY DISEASE OF MUCOUS MEMBRANE
    1) CASE REPORT: Contact stomatitis was reported in a 71-year-old woman who had a positive patch test to the methyl methacrylate monomer extracted from her dentures which have been in use for 15 years and which could have been incompletely polymerized (Kanzaki et al, 1989).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) Methyl methacrylate administered to rats at 2 mmol/kg by gavage did not cause significant gastric edema (Ghanayem et al, 1985).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) Transient but dose-related elevation of serum gamma glutamyl transferase was reported in a patient who underwent hip replacement with polymethyl methacrylate bone cement (Pople & Phillips, 1988).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC ENZYMES INCREASED
    a) RATS exposed to 25 mg MMA twice weekly showed decreases in serum glycoprotein and albumin levels and increases in other hepatic enzymes (Motoc et al, 1971).
    2) HEPATIC NECROSIS
    a) RHESUS MONKEY: Centrilobular necrosis of the liver was found in a rhesus monkey which died in coma after an accidental 22-hour exposure to the vapor (Gosselin et al, 1984).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) Allergic contact dermatitis has been reported (Foussereau et al, 1989; Pegum & Medhurst, 1971; Kanerva et al, 1993). Other acrylic monomers may cross-react and produce similar dermatitis (Fisher, 1980a; Lovell et al, 1985).
    2) The contact dermatitis is characterized by paresthesia and tenderness that outlast the eruption (Ellenhorn & Barceloux, 1988).
    3) CASE REPORT: Erythroderma, hypertension and dyspnea developed acutely in a nurse after repeated exposures to a surgical cement containing 97% methyl methacrylate monomer (Scolnick & Collins, 1988).
    4) CASE REPORT: Pruriginous papulo-erythematous lesions with some degree of hyperkeratosis erupted near the amputation stump and spread to rest of the body sparing the face and the scalp when a man revarnished his lower leg prosthesis with methacrylates. A patch test was positive for methyl methacrylate (Romaguera et al, 1989).
    B) NAIL FINDING
    1) Eczematous reactions of onychial and paronychial tissues have been reported in patients using acrylic plastic nails. Dystrophic nail changes may persist for years; irreversible loss of the fingernails has occurred (Fisher, 1980) 1989; 1990). Methyl methacrylate is no longer used in artificial nail products (Fisher, 1980) 1990).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) Sensitization and allergic contact dermatitis have been reported (Scolnick & Collins, 1988; (Fisher, 1989; Foussereau et al, 1989; Romaguera et al, 1989; Kanerva et al, 1988; Kanerva et al, 1993; Guerra et al, 1993).
    2) CASE REPORT: A 31-year-old nurse exposed to methyl methacrylate vapors developed diffuse erythroderma, dyspnea, headache, hypertension, lethargy, and lightheadedness (Scolnick & Collins, 1986).
    3) Occupational asthma has been reported in persons exposed to methyl methacrylate and polymethyl methacrylate (Lozewicz et al, 1985).

Reproductive

    3.20.1) SUMMARY
    A) There is no evidence of methyl methacrylate-induced teratogenicity in humans but there are conflicting reports in animals.
    3.20.2) TERATOGENICITY
    A) HUMAN EXPOSURE
    1) LACK OF EFFECT
    a) No adverse effects on human reproductive function have been reported. Occupational exposure is unlikely to present a reproductive hazard (AMA, 1985).
    B) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) No teratogenic effects were produced in the fetuses of pregnant mice exposed for 60 hours to levels of 116 and 400 ppm of methyl methacrylate monomer vapor (Tansy & Kendall, 1979).
    2) FETOTOXICITY
    a) Lower fetal weight gains have been observed (Singh et al, 1972).
    3) SKELETAL MALFORMATION
    a) RATS - 27,500 ppm given for 54 minutes to pregnant rats on days 6 to 15 of gestation caused maternal toxicity and significant increases in fetal deaths, hematomas, and skeletal anomalies (Nicholas et al, 1979).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) Pregnant rats exposed to an airborne concentration of 27,500 ppm for 54 minutes on days 6 to 15 of gestation developed maternal toxicity and there were significant increases in fetal deaths, hematomas, and skeletal anomalies (RTECS , 2000; Nicholas et al, 1979).
    2) Methacrylate esters given to pregnant rats on days 5, 10, and 15 of gestation resulted in hemangiomas, increased resorptions, and decreased fetal weights (HSDB , 2000).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS80-62-6 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Methyl methacrylate
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.2) SUMMARY/HUMAN
    A) Long-term follow-up of workers does not support the carcinogenicity of methylmethacrylate but chronic exposure in animals has been associated with fibrosarcomas (Anon, 1994; HSDB , 2000).
    B) At the time of this review, no data concerning the carcinogenicity of methyl methacrylate was found in documents by the National Toxicology Program (US DHHS, 1994), NIOSH (Chemsoft(R) , 1996) or in IRIS (IRIS, 1996).
    3.21.3) HUMAN STUDIES
    A) GASTRIC CARCINOMA
    1) CASE SERIES - Increased prevalence of mortality from colon cancer in persons with the greatest exposure was reported in an epidemiologic study of workers at two acrylic sheet manufacturing plants (Walker et al, 1991). Cause-effect is difficult to determine, since the workers were exposed to other chemicals in addition to methyl methacrylate and exposures were not directly measured (Walker et al, 1991; Anon, 1994).
    2) Increased mortality from colon and rectal cancer was noted in male employees who had been exposed to acrylate monomers, including methyl methacrylate, for at least 10 months (ACGIH, 1991).
    B) LACK OF EFFECT
    1) CASE SERIES - A well-designed cohort study of 2,671 men, 1,561 of whom were exposed to methyl methacrylate, showed no statistically significant excess of cancer rates and all-cause or cause-specific mortalities. No trend was shown on analysis of dose of methyl methacrylate with several cancer sites (Collins et al, 1989).
    3.21.4) ANIMAL STUDIES
    A) NEOPLASM
    1) Rats and mice exposed to MMA vapors at airborne levels of 250 to 1,000 ppm did not develop cancer; inflammation and epithelial hyperplasia of the nasal cavity and degeneration of the olfactory sensory epithelium were observed (NTP, 1986).
    2) An increased incidence of local fibrosarcomas was reported with subcutaneous implants of polymerized methyl methacrylate in rats for up to 39 months (NRC, 1977).

Genotoxicity

    A) Methyl methacrylate induced mutations in bacterial cells (Poss et al, 1979) and caused breaks and rearrangements in chromatids and/or chromosomes of cultured L5178Y mouse lymphoma cells (Moore et al, 1988).

Summary Of Exposure

    A) USES: Methyl methacrylate is used in the production of acrylics, clear plastics, marble-like surfaces, extrusion powders, paints and inks, adhesive cements, industrial flooring compositions, precast concrete composites, resin mortars, polishes, dental fillers, surgical implants, and bone cements.
    B) TOXICOLOGY: Methyl methacrylate decreases the amplitude of the action potential in peripheral nerves by causing lysis of membrane lipids and destruction of the myelin sheath. It is an irritant and sensitizer, and can cause bronchospasm and dermatitis. At high concentrations, it has CNS and respiratory depressant effects. It is thought to promote granuloma formation and trigger focal bone resorption.
    C) EPIDEMIOLOGY: Exposure to liquid methyl methacrylate is generally occupational. It is usually found as a commercial or technical grade (99.8% pure) which contains inhibitors such as hydroquinone or monomethyl ether of hydroquinone to prevent polymerization. Once polymerized, it is inert.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY
    a) ORAL: Significant systemic toxicity is not expected after acute ingestion. If an object made from the polymer is ingested, it presents a potential foreign body (choking) hazard.
    b) DERMAL: Irritation dermatitis, allergic contact dermatitis, numbness, paresthesias, cold sensation in extremities, and cutaneous burns may occur. Eczematous reactions of onychial and paronychial tissues have been reported in patients using acrylic plastic nails. Dystrophic nail changes may persist for months. Irreversible loss of the fingernails has occurred.
    c) INHALATION: Occupational exposure through inhalation has resulted in asthma, narcosis, headache, dizziness, extremity pain, fatigue, sleep disturbances, irritability, memory loss, depression, laryngitis, anorexia, nausea, drowsiness, and decrement in olfactory ability.
    d) OCULAR: Corneal irritation and lens opacity may occur.
    2) SEVERE TOXICITY
    a) INHALATION: Can cause drowsiness, CNS or respiratory depression.
    b) DERMAL: Chronic exposure can cause peripheral neuropathy.
    c) OTHER: Systemic vasodilation and transient hypotension have been reported following use as a bone cement in total hip replacement procedures. Methacrylic acid-containing primers used in artificial nail cosmetic products are highly corrosive and have been associated with respiratory toxicity and cutaneous burn. Refer to "ACIDS" management for information on methacrylic acid.

Heent

    3.4.3) EYES
    A) Methyl methacrylate is moderately irritating to eyes (Clayton & Clayton, 1994; Lewis, 1996). Within minutes of exposure to 110 ppm, rats exhibited behavior suggestive of eye discomfort (Oberly & Tansy, 1985).
    B) CORNEAL IRRITATION: Ocular exposure in rabbits resulted in corneal irritation which lasted several days after exposure (Clayton & Clayton, 1994; NIOSH, 1976).
    1) A localized fibrin mass, damage of corneal endothelium, and swelling of cornea with partial vascularization developed acutely when 10 microliters of methyl methacrylate were injected into the anterior chamber of rabbits (Holyk & Eifrig, 1979).
    C) LENS OPACITY AND IRIS ATROPHY: Anterior lens opacity and areas of iris atrophy developed later in rabbit eyes instilled with MMA (Holyk & Eifrig, 1979).
    3.4.5) NOSE
    A) IRRITATION: Methyl methacrylate is moderately irritating to the nose (NIOSH, 1976).
    B) OLFACTORY DYSFUNCTION: A dose-response relationship between olfactory dysfunction and cumulative exposure scores was identified in a case-control study involving 731 study volunteers who worked in a plant which manufactured methyl methacrylate, ethyl acrylate, butyl acrylate and acrylic acid. The decrement in olfaction was not clinically apparent and reflected a reversible, physiologic impairment (Schwartz et al, 1989).
    1) Acute exposure was not associated with olfactory dysfunction, as determined by cross-sectional data analysis with exposure based on job category (Schwartz et al, 1989).
    2) In a German study, an acute exposure of 20 healthy volunteers to 50 ppm of methyl methacrylate resulted in only minor irritation of the nasal mucosa, but no inflammatory changes in nasal epithelium and impairment of mucociliary transport or olfactory functioning were observed (Muttray et al, 2015).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Systemic vasodilation and transient hypotension have been reported following use as a bone cement in total hip replacement procedures (Duncan, 1989).
    B) HYPERTENSIVE EPISODE
    1) CASE REPORT: Acute hypertension, erythroderma and dyspnea developed in a nurse after repeated exposures to a surgical cement containing 97% methyl methacrylate monomer (Scolnick & Collins, 1986).
    C) CARDIAC ARREST
    1) Reports of cardiac arrest, and fat and bone marrow embolism are presumably due to heat and pressure in the femoral canal while the polymer is curing (Merin, 1983).
    D) ATRIOVENTRICULAR BLOCK
    1) A patient developed transient episodes of atrioventricular block on 2 occasions, 4 weeks apart, immediately after insertion of MMA cement into the femoral cavity (Brown & Parmley, 1982).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CARDIAC FAILURE
    a) MYOCARDIAL DEPRESSION: MMA monomer has been shown to have a direct myocardial depressant effect on isolated perfused rabbit heart (Mir et al, 1973; Wong et al, 1977).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) Occupational asthma has been associated with the use of various methyl methacrylate compounds (Pickering et al, 1986; Lozewicz et al, 1985).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RESPIRATORY DEPRESSION
    a) Respiratory depression been reported in some animal studies involving high dose IV exposure (Deichmann, 1941), but a study involving repeated 4 hr exposure of rats to 110 ppm reported no adverse respiratory effects (Oberly & Tansy, 1985).
    2) HYPERVENTILATION
    a) Transient tachypnea has been reported in some animal studies involving IV doses of 0.03 mL/kg IV (Deichmann, 1941), but another study involving repeated 4 hr exposure of rats to 110 ppm reported no respiratory distress (Oberly & Tansy, 1985).
    3) PULMONARY EDEMA
    a) Atelectasis and emphysema were found in a rhesus monkey which died in coma after an accidental 22-hour exposure to the vapor (Kessler et al, 1977).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) PARESTHESIA
    1) Chronic paresthesias can occur and may outlast dermatitis associated with the exposure (Pegum & Medhurst, 1971; Fisher, 1990; Donaghy et al, 1991).
    B) SECONDARY PERIPHERAL NEUROPATHY
    1) Peripheral neuropathy developed in a dental technician following 30 yrs of dermal and inhalational exposure to methyl methacrylate while forming dental prostheses (Donaghy et al, 1991).
    a) Clinical effects included paresthesias of the fingers, loss of manual dexterity, impaired peripheral sensation, muscle wasting, hand and limb weakness, and depressed or absent reflexes. Electrophysiologic tests indicated a generalized sensorimotor neuropathy with axonal degeneration (Donaghy et al, 1991).
    2) Dental technicians who used bare hands to mold methyl methacrylate putty had significantly slower distal sensory conduction velocities from the digits, implicating mild axonal degeneration in the area of contact with MMA (Rajaniemi et al, 1989; Seppalainen & Rajaniemi, 1984).
    C) HEADACHE
    1) Headache and irritability or excitement may occur (Lewis, 1996; Scolnick & Collins, 1986).
    D) DROWSY
    1) Inhalation of methyl methacrylate vapor can cause dizziness and narcosis (ILO, 1983; Lewis, 1996).
    2) Nail sculptors exposed to methyl methacrylate dusts and vapors, in addition to exposure to other methacrylates, methacrylic acid and solvents, had consistently more complaints of nose and skin irritation, drowsiness, dizzy spells, and trembling of hands, as compared to controls. The differences were not statistically significant (Hiipakka & Samimi, 1987).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEUROPATHY
    a) RATS exposed to 400 ppm of monomer vapor for 60 minutes showed decreased neuronal firing rate (Innes & Tansy, 1981).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific lab work or diagnostic procedures should be done in the acute setting unless otherwise clinically indicated.
    B) Nerve conduction studies and pulmonary function tests may be conducted to document possible chronic effects of exposure on peripheral nerves and pulmonary effects.
    C) Patch testing may aid in differentiating irritant dermal effects from allergic dermal responses. This information is used to identify sensitized individuals who should be removed from further exposure.
    4.1.2) SERUM/BLOOD
    A) No specific lab work or diagnostic procedures should be done in the acute setting unless otherwise clinically indicated.
    4.1.4) OTHER
    A) OTHER
    1) OTHER
    a) Nerve conduction studies and pulmonary function tests may be conducted to document possible chronic effects of exposure on peripheral nerves and pulmonary effects.
    2) ELECTROPHYSIOLOGICAL TESTING
    a) Nerve conduction studies have been conducted to document possible effects of exposure on peripheral nerves (Seppalainen & Rajaniemi, 1984; Rajaniemi et al, 1989; Donaghy et al, 1991).
    3) DERMAL
    a) Patch testing may aid in differentiating irritant dermal effects from allergic dermal responses (Lewis, 1990). This information is used to identify sensitized individuals who should be removed from further exposure.
    4) PULMONARY FUNCTION TESTS
    a) Pulmonary function tests may be useful to identify pulmonary effects such as asthma; however, normal pulmonary function tests cannot be used to exclude the diagnosis of asthma (Sheppard et al, 1990). Some asthmatics have normal pulmonary function when tested.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with CNS depression or persistent pulmonary irritation should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients who are asymptomatic or have only mild irritation can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear. An industrial hygienist and/or occupation medicine specialist may be useful to evaluate workplace exposures.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with deliberate exposure, or more than mild irritation should be referred to a healthcare facility.

Monitoring

    A) No specific lab work or diagnostic procedures should be done in the acute setting unless otherwise clinically indicated.
    B) Nerve conduction studies and pulmonary function tests may be conducted to document possible chronic effects of exposure on peripheral nerves and pulmonary effects.
    C) Patch testing may aid in differentiating irritant dermal effects from allergic dermal responses. This information is used to identify sensitized individuals who should be removed from further exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Significant systemic toxicity is not expected after acute ingestion; gastrointestinal decontamination is generally not warranted.
    6.5.2) PREVENTION OF ABSORPTION
    A) Significant systemic toxicity is not expected after acute ingestion; gastrointestinal decontamination is generally not warranted.
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) No specific lab work or diagnostic procedures should be done in the acute setting unless otherwise clinically indicated.
    2) Nerve conduction studies and pulmonary function tests may be conducted to document possible chronic effects of exposure on peripheral nerves and pulmonary effects.
    3) Patch testing may aid in differentiating irritant dermal effects from allergic dermal responses. This information is used to identify sensitized individuals who should be removed from further exposure.
    B) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Remove from exposure and give supplemental oxygen if necessary. Treat bronchospasm with inhaled beta agonists.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persists, an ophthalmologic exam should be performed.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) Remove contaminated clothing and wash exposed area thoroughly with soap and water. Treat contact dermatitis with topical corticosteroids.

Range Of Toxicity

Summary

    A) TOXICITY: At concentrations of 0.5 to 5 ppm, workers report frequent headaches, pain in the extremities, irritability, loss of memory, excessive fatigue, and sleep disturbances. With air concentrations from 3 to 77 ppm, surgical assistants who mixed methyl methacrylate bone cement in operating rooms described occasional transient eye irritation. TLV-TWA: 50 ppm. NIOSH: TWA: 100 ppm (410 mg/m(3)); IDLH: 1000 ppm; OSHA PEL: 8-hour TWA: 100 ppm (410 mg/m(3)).

Maximum Tolerated Exposure

    A) ACUTE
    1) TLV-TWA: 50 ppm. NIOSH: TWA: 100 ppm (410 mg/m(3)); IDLH: 1000 ppm; OSHA PEL: 8-hour TWA: 100 ppm (410 mg/m(3)) (American Conference of Governmental Industrial Hygienists, 2010; U.S. Occupational Safety, and Health Administration (OSHA), 2010; National Institute for Occupational Safety and Health, 2007).
    2) TCLo (INHL) HUMAN: 125 ppm (RTECS , 2000)
    3) TCLo (INHL) HUMAN: 60 mg/m(3) (RTECS , 2000)
    B) Numbness, coldness, and paresthesia of the fingers have been reported among people who handle the monomer with their bare hands, most notably among dental technicians who mold methyl methacrylate putty. Allergic contact dermatitis as well as occupational asthma have been reported among workers who have been reexposed to methyl methacrylate liquid (ACGIH, 1999; (Hathaway et al, 1996; Raffle et al, 1994).
    C) CONCENTRATION LEVEL
    1) In a German study, an acute exposure of 20 healthy volunteers to 50 ppm of methyl methacrylate resulted in only minor irritation of the nasal mucosa, but no inflammatory changes in nasal epithelium and impairment of mucociliary transport or olfactory functioning were observed (Muttray et al, 2015).
    2) At concentrations of 0.5 to 50 parts per million, 78% of 152 exposed workers reported frequent headaches, 30% reported pain in the extremities, 10% reported irritability, 20% reported loss of memory, and 21% reported excessive fatigue and sleep disturbance (Blagodatin et al, 1976).
    3) At levels of 4 to 49 parts per million, workers in plants manufacturing polymethyl methacrylate sheets had no observable effects in terms of symptomatology and changes in blood pressure, respiratory function testing, hemoglobin and white blood count, urinalysis, and blood chemistry (Cromer J & Kronoveter K, 1976).
    4) With air levels from 3 to 77 parts per million, surgical assistants who mixed methyl methacrylate bone cement in operating rooms described occasional transient eye irritation (NIOSH, 1977).
    5) With exposures higher than 49 parts per million, statistically insignificant effects on serum glucose, blood urea nitrogen, cholesterol, albumin, and total bilirubin levels were noted among workers (Cromer J & Kronoveter K, 1976).
    6) 170 to 250 ppm causes irritation, 2300 ppm is intolerable (NIOSH, 1976).
    7) At concentrations of 100 to 599 mg/m(3), 75% of 300 exposed Soviet women developed irritability, fatigue, headache, and mucous membrane irritation (Dobrinsky, 1970).
    8) 150 mg/m(3) produce CNS effects when inhaled by humans (Gosselin et al, 1984).

Workplace Standards

    A) ACGIH TLV Values for CAS80-62-6 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Methyl methacrylate
    a) TLV:
    1) TLV-TWA: 50 ppm
    2) TLV-STEL: 100 ppm
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: SEN
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    b) SEN: The designation SEN refers to the potential for an agent to produce sensitization, as confirmed by human or animal data. The notation does not imply that this is the critical effect or that this is the sole basis for the TLV. Although, for those TLVs that are based on sensitization, the TLV is meant to protect workers from induction of this effect, but cannot protect workers who have already become sensitized. The notation should be used to assist in identifying sensitization hazards and reducing respiratory, dermal, and conjunctival exposures to sensitizing agents in the workplace. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): URT and eye irr; body weight eff; pulm edema
    d) Molecular Weight: 100.13
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS80-62-6 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Methyl methacrylate
    2) REL:
    a) TWA: 100 ppm (410 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 1000 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS80-62-6 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Methyl methacrylate
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): E ; Listed as: Methyl methacrylate
    a) E : Evidence of non-carcinogenicity for humans.
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Methyl methacrylate
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Methyl methacrylate
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS80-62-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Methyl methacrylate
    2) Table Z-1 for Methyl methacrylate:
    a) 8-hour TWA:
    1) ppm: 100
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 410
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 945 mg/kg -- Somnolence (general depressed activity) (RTECS , 2000)
    B) LD50- (ORAL)MOUSE:
    1) 3625 mg/kg (RTECS , 2000)
    C) LD50- (SUBCUTANEOUS)MOUSE:
    1) 5954 mg/kg -- Somnolence (general depressed activity) (RTECS , 2000)
    D) LD50- (INTRAPERITONEAL)RAT:
    1) 1328 mg/kg (RTECS , 2000)
    E) LD50- (ORAL)RAT:
    1) 7872 mg/kg -- Muscle Weakness; Coma; Respiratory depression (RTECS , 2000)
    F) LD50- (SUBCUTANEOUS)RAT:
    1) 7088 mg/kg -- Somnolence (general depressed activity) (RTECS , 2000)
    G) TCLo- (INHALATION)HUMAN:
    1) 125 ppm -- Effect on sleep; Excitement; Anorexia (RTECS , 2000)
    2) 60 mg/m(3) -- Effects on sleep; Excitement; Blood pressure lowering not characterized in autonomic section (RTECS , 2000)
    H) TCLo- (INHALATION)MOUSE:
    1) 41 g/m(3) for 90M for 15D- intermitent -- Death (RTECS , 2000)
    2) 5000 ppm for 6H for 14W- intermittent -- Other changes in sense organs and special senses (Nose, Eye, Ear, and Taste); Hepatitis (hepatocellular necrosis), zonal; Death (RTECS , 2000)
    3) 500 ppm for 6H for 2Y- intermittent -- Other changes in sense organs and special senses (Nose, Eye, Ear, and Taste); Fibrosis, focal (pneumoconiosis) (RTECS , 2000)
    I) TCLo- (INHALATION)RAT:
    1) Female, 54 mg/m(3) for 24H at 8W prior to mating -- Menstrual cycle changes or disorders (RTECS , 2000)
    2) Female, 4480 mg/m(3) for 2H at 6-18D of pregnancy -- Post-implantation mortality (e.g., dead and or resorbed implants per total number of implants) (RTECS , 2000)
    3) Female, 109 g/m(3) for 17M at 6-15D of pregnancy -- Fetotoxicity (except death, e.g., stunted fetus); Developmental abnormalities in musculoskeletal system (RTECS , 2000)
    4) Female, 109 g/m(3) for 54M at 6-15D of pregnancy -- Fetal death; Other developmental abnormalities (RTECS , 2000)
    5) 116 ppm for 8H/D for 26W- intermittent -- Changes in serum composition (e.g., TP, bilirubin, cholesterol); Nutritional and Gross Metabolic (P); Effects on transaminases (RTECS , 2000)
    6) 1 mg/m(3) for 24H for 60D- continuous -- Muscle contraction or spasticity; Effect on true cholinesterase; Porphyrin including bile pigments (RTECS , 2000)
    7) 115 mg/m(3) for 3H for 17W- intermittent -- EKG changes not diagnostic of above; Other blood changes (RTECS , 2000)
    8) 34,500 mg/m(3) for 16W- intermittent -- Fatty liver degeneration; Changes in kidney, ureter, and Bladder; Effetc on amino acids (including renal excretion) (RTECS , 2000)
    9) 5000 ppm for 6H for 14W- intermittent -- Changes in circulation of brain and coverings (hemorrhage, thrombosis, etc.); Other changes in sense organs and special senses (Nose, Eye, Ear, and Taste); Death (RTECS , 2000)
    10) 500 ppm for 6H for 2Y- intermittent -- Other changes in sense organs and special senses (Nose, Eye, Ear, and Taste); Fibrosis, focal (pneumoconiosis) (RTECS , 2000)

Pharmacology Toxicology

Toxicologic Mechanism

    A) NEUROLOGIC EFFECTS -
    1) MMA decreases the amplitude of the action potential in peripheral nerves (Borchard, 1981).
    2) High concentrations which caused CNS effects have been shown to be due to the desheathing of the sciatic nerve and hyperpolarization of the resting potential in the amphibian (Bohling et al, 1977).
    3) Another but similar mechanism of neurologic toxicity is the diffusion of MMA into the nerve cells causing lysis of membrane lipids and destruction of the myelin sheath (Proctor et al, 1988). Electrophysiologic tests and nerve biopsy in a human chronically exposed to methyl methacrylate showed sensorimotor neuropathy with axonal degeneration and other effects similar to those associated with acrylamide exposure (Donaghy et al, 1991).
    B) PULMONARY EFFECTS -
    1) The direct bronchospastic effect of MMA is thought to be the cause of the tachypnea (Scolnick & Collins, 1986).
    2) MMA has a direct respiratory depressant effect, which may cause apnea (Deichmann, 1941).
    C) OSTEOLYSIS - Polymethylmethacrylate in bone cement implants has been shown to promote granuloma formation and trigger focal bone resorption (Griffiths et al, 1987; Willert et al, 1990). When compared to cryosurgery, though, polymethylmethacrylate did not cause bone necrosis in dogs (Malawer et al, 1988).
    D) FAT EMBOLISM - Traces of MMA cement may activate atypical lipids which tend to coalesce in the pulmonary circulation (Duncan, 1989).
    E) CONTACT LENS-INDUCED EDEMA - Polymethyl methacrylate contact lens caused corneal swelling by fluid absorption across the endothelial layer and not by direct inhibition of epithelial and endothelial ion transport inhibition (Huff, 1990).

Physicochemical

Physical Characteristics

    A) Methyl methacrylate is a flammable, clear, colorless liquid; its odor has been described as distinctive, fruity, ester-like, acrid, and pungent. Methyl methacrylate monomer is a polymerization hazard when exposed to light, heat, oxygen, or ionizing radiation (AAR, 1998; ACGIH, 1999; (Ashford, 1994; Clayton & Clayton, 1994; ILO, 1998; Lewis, 1996; Lewis, 1997; Lewis, 1997; Verschueren, 1983).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 100.13 (RTECS , 2000)

Other

    A) ODOR THRESHOLD
    1) 0.083 (ACGIH, 1999)

References

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