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ACRYLATES, MULTIFUNCTIONAL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Multifunctional acrylates can be found in a variety of products acting as hardeners and sealants.

Specific Substances

    A) COMPONENTS OF THE GROUP
    1) Diethyleneglycol diacrylate (DEGDA)
    2) Diethyleneglycol dimethacrylate (DEDMA)
    3) Dipentaerythritol monohydroxy penta acrylate (DEMPA)
    4) Dipropyleneglycol diacrylate (DPGDA)
    5) Ethyleneglycol diacrylate (EGDA)
    6) Ethyleneglycol dimethacrylate (EGDMA)
    7) Glycerol propoxydiacrylate
    8) Glycerol propoxytriacrylate
    9) MFA (multifunctional acrylates)
    10) Multifunctional acrylates
    11) Neopentylglycol diacrylate (NPGDA)
    12) Neopentylglycol dimethacrylate (NPGDMA)
    13) Oligotriacrylate OTA 480
    14) Pentaerythritol tetraacrylate (PETTA)
    15) Pentaerythritol triacrylate (PETA)
    16) Tetraethyleneglycol diacrylate (TTEGDA or TEGDA)
    17) Tetraethyleneglycol dimethacrylate (TTEGDMA)
    18) Triethyleneglycol diacrylate (TREGDA)
    19) Triethyleneglycol dimethacrylate (TREGDMA)
    20) Trimethylolpropane triacrylate (TMPTA)
    21) Trimethylolpropane trimethylacrylate (TMPTMA)
    22) Tripropyleneglycol diacrylate (TRPGDA or TPGDA)
    23) Urethane acrylate (UA)
    24) 1,4-Butanediol diacrylate (BDA or BUDA)
    25) 1,4-Butanediol dimethacrylate (BDMA)
    26) 1,6-Hexanediol diacrylate (HDODA)
    27) 1,6-Hexanediol dimethacrylate (HDODMA)
    28) 2-Hydroxyethyl acrylate (HEA)
    29) 2-Hydroxyethyl methacrylate (HEMA)
    30) 2-Hydroxypropyl acrylate (HPA)
    31) Hydroxy methacrylate
    32) Hydroxy propyl methacrylate
    33) Polyethylene glycol dimethacrylate
    34) Polyurethane dimethacrylate
    35) Tetrahydrofurfuryl methacrylate

Available Forms Sources

    A) FORMS
    1) GENERAL - These monomers are more complex than low molecular weight acrylates. They are "cured" by UV light which causes instant binding and cross-linking of the polymers (Scolnick, 1992). The result of the UV-induced cross-linking is almost instantaneous setting and drying of the coatings or inks (Andrews & Clary, 1986; Nethercott et al, 1983).
    2) ANAEROBIC ACRYLIC SEALANTS - These liquids polymerize rapidly in the absence of oxygen and in the presence of metals, such as chromium, iron, manganese, and others (Conde-Salazar et al, 1988).
    3) Trade Names
    a) Loctite(R)
    b) 200 series (222, 242, 270, and 290): locking and sealing
    c) 600 series (601, 638, 641, and 648): retention of ball bearings
    d) 500 series (510, 573, 542, and 572): formation and sealing joints
    e) 300 and 400 series (326, 330, 415, and 495): immediate adhesives
    f) Duro(R)
    g) Sta-Lok(R)
    h) Treebond(R)
    4) GENERAL FORMULATIONS (Ranchoff & Taylor, 1985) -
    a) Dimethacrylates (DMA)
    1) Ethylene glycol DMA
    2) Ethoxylated bisphenol A DMA
    3) Polyurethane DMA
    4) Tri-, tetra-, and polyethylene glycol DMA
    b) Diacylates (DA)
    1) Dicyclopentenyloxyethyl acrylate
    2) Ethylene Glycol DA
    3) Ethoxylated bisphenol A DA
    4) Polyurethane DA
    5) Tri-, tetra-, and polyethylene glycol DA
    c) Alkyl methacrylates (MA)
    1) Hydroxyethyl MA
    2) Hydroxypropyl MA
    3) Isobutyl MA
    4) Tetrahydrofurfuryl MA
    d) Alkyl acrylate (A)
    1) Amino A
    2) Cyano A (always mixed with other acrylates)
    3) Hydroxyethyl A
    4) Hydroxypropyl A
    e) Components
    1) Monomer
    2)
    a) Acrylates/dimethacrylates
    3) Polymerization initiators
    4)
    a) Cumene hydroperoxide
    5) Polymerization accelerators
    6)
    a) Dialkyl arylamines
    7) Hydrazines
    8) Saccharin-based compounds
    9) Trialkylamines
    10) Thixotropes
    11) Silicon dioxide
    12) Proprietary chemicals
    13) Thickeners
    14) Coumarone-indene resin
    15) Lubricants
    16) Pigments and dyes
    17) Polymerization Stabilizers
    18) Quinones
    19) Fillers
    20) Cellulose acetate butyrate
    5) ULTRAVIOLET CURING INKS -
    a) Napp(R) (Pedersen et al, 1983) 2-hydroxyethyl methacrylate N,N'-methylene-bis-acrylamide
    b) Nyloprint WD(R) (Pedersen et al, 1983) 2-hydroxyethyl methacrylate
    6) AZIRIDINE PAINT HARDENER -
    a) Polyfunctional aziridine cross-linker or hardener is made by reacting propyleneimine or ethyleneimine with a polyfunctional acrylate such as trimethylolpropane triacrylate (TMPTA) or pentaerythritol triacrylate (PETA) (Cofield et al, 1985).
    b) These hardeners are self-curing in that they require no ultraviolet radiation to cross-link acrylic polymers. Drying may occur more rapidly if heat is applied (Cofield et al, 1985).
    c) These hardeners may be found in paints, paint primers, lacquers, topcoats, undercoats, and other protective coatings (Cofield et al, 1985).
    B) SOURCES
    1) Acrylates can be prepared by dehydration of a corresponding hydroxyalkanoic acid, saponification of alkene nitrile, catalytic hydration of acetylene and carbon monoxide, or the reaction of acetone with hydrocyanoic acid (HSDB , 2001).
    2) 1,6-Hexanediol diacrylate is prepared by the esterification of 1,6-Hexanediol with acrylic acid (HSDB , 2001).
    C) USES
    1) GENERAL -
    a) Multifunctional acrylates are used in photocurable coatings and inks.
    b) Ultraviolet-cured polyacrylates are used in the manufacturing of soft, disposable contact lenses (Peters & Andersen, 1986).
    c) Ultraviolet-cured coatings have been applied to teeth as a dental sealant (Nethercott, 1978).
    2) ANAEROBIC ACRYLIC SEALANTS - Many of the same acrylic compounds used as anaerobic sealants are also used in paint-on artificial self-curing nail extenders (Ranchoff & Taylor, 1985).
    3) AZIRIDINE HARDENERS - These are used in printing inks (Garabrant, 1985) and in plastic flooring materials to increase the wearing properties and ease of cleaning of the flooring (Dahlquist et al, 1983).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) Multifunctional acrylates (MFAs) are not considered an acute hazard following ingestion. Based on animal studies, the acute oral toxicity generally increases as the molecular weight of the acrylate decreases.
    2) Percutaneous absorption resulting in systemic toxicity and death has been reported in experimental laboratory animals. Low molecular weight MFAs are absorbed better percutaneously than following ingestion in animal studies.
    3) These compounds can potentially cause severe eye irritation. Skin irritation and sensitization are associated with occupational contact exposure.
    0.2.4) HEENT
    A) WITH POISONING/EXPOSURE
    1) Some of these compounds can cause conjunctivitis, severe eye irritation, or corrosive injury following eye exposure.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Fatigue, headache, and numbness of the tongue were reported following dermal exposure in one worker.
    2) HEA (2-hydroxyethyl acrylate) had minimal neurotoxic potential in one animal study.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Nausea and vomiting have been reported following dermal exposure in one worker.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Skin irritation, necrosis, and allergic contact dermatitis have been reported in workers.
    0.2.19) IMMUNOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Many multifunctional acrylates cause dermal sensitization. Systemic symptoms associated with patch testing with 2-HEMA, 2-HEA, and EGDMA were reported in one case. Animal studies have shown that multifunctional acrylates are poor immunogens compared to monofunctional acrylates.
    0.2.20) REPRODUCTIVE
    A) No human data were found at the time of this review with the exception of 1 case of menstrual irregularities from exposure to several acrylates. Animal studies at the time of this review did not show conclusive evidence of fetotoxicity or teratogenicity.

Laboratory Monitoring

    A) Specific laboratory measures are not indicated.
    B) Patch tests may aid in determining agents responsible for allergic responses and can be used to eliminate exposure to the causative agent.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    B) Exposed individuals should have a careful, thorough medical history and physical examination performed, looking for any abnormalities. Exposure to chemicals with a strong odor often results in such nonspecific symptoms as headache, dizziness, weakness, and nausea.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    C) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Range Of Toxicity

    A) Minimum lethal human exposure is unknown.
    B) Sensitized individuals may react to any subsequent exposure.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) Multifunctional acrylates (MFAs) are not considered an acute hazard following ingestion. Based on animal studies, the acute oral toxicity generally increases as the molecular weight of the acrylate decreases.
    2) Percutaneous absorption resulting in systemic toxicity and death has been reported in experimental laboratory animals. Low molecular weight MFAs are absorbed better percutaneously than following ingestion in animal studies.
    3) These compounds can potentially cause severe eye irritation. Skin irritation and sensitization are associated with occupational contact exposure.

Heent

    3.4.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Some of these compounds can cause conjunctivitis, severe eye irritation, or corrosive injury following eye exposure.
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CONJUNCTIVITIS: Irritant contact conjunctivitis has been reported in workers using multifunctional acrylates in printing press inks (Nethercott, 1978).
    B) ANIMAL STUDIES
    1) RABBIT: CORROSIVE: Many of the MFAs are severe eye irritants or corrosive when instilled into rabbit eyes in the Draize test (HSDB , 2001; Andrews & Clary, 1986).
    2) RABBIT - NONIRRITATING: HDODA, TMPTMA, TRPGDA, and TTEGDMA are nonirritating when instilled into rabbit eyes in the Draize test (Andrews & Clary, 1986).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) TONGUE NUMBNESS: A 30-year-old woman developed numbness of the tongue associated with skin contact of HEMA and HEA (Andersen, 1986).

Respiratory

    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) RATS: Diethylene glycol diacrylate (DGDA) appears to have low toxicity following inhalational exposure. Rats, exposed to a DGDA-saturated atmosphere for 8 hours at room temperature, did not appear to exhibit any serious adverse effects (HSDB , 2001).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Fatigue, headache, and numbness of the tongue were reported following dermal exposure in one worker.
    2) HEA (2-hydroxyethyl acrylate) had minimal neurotoxic potential in one animal study.
    3.7.2) CLINICAL EFFECTS
    A) FATIGUE
    1) WITH POISONING/EXPOSURE
    a) Fatigue has been reported with workplace exposure to compounds including 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, and ethyleneglycol dimethacrylate (Andersen, 1986).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) RATS: No neuropathological changes and minimal neurobehavioral effects occurred in rats following intraperitoneal injection of 2-hydroxyethyl acrylate (HEA) at 3, 20 or 60 mg/kg daily for 5 days/week over 13 weeks (Moser et al, 1992). In contrast, the structurally similar chemical, acrylamide, produced pronounced neuromuscular defects and axonal degeneration.

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Nausea and vomiting have been reported following dermal exposure in one worker.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 30-year-old woman developed systemic symptoms including nausea and vomiting associated with skin contact with HEMA and HEA (Andersen, 1986).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Skin irritation, necrosis, and allergic contact dermatitis have been reported in workers.
    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) MFAs should be considered to have potential for producing skin irritation (Andrews & Clary, 1986).
    b) Delayed irritation (no immediate sensation of irritation) has been reported from occupational exposure to HPA (Lovell et al, 1985), BDA, HDODA, and TTEGDA (HSDB , 2001; Nethercott et al, 1984; Malten et al, 1979). In two cases, blisters developed 5 to 6 hours after exposure (Lovell et al, 1985).
    B) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Multifunctional acrylates are considered more potent allergens than monomeric acrylate allergens (Nethercott, 1978; Bjorkner, 1984a). Contact with the cured ink or coating is unlikely to result in cutaneous problems in those handling it (Nethercott, 1978).
    b) In general, MFAs should be considered potential sensitizers (Andrews & Clary, 1986; Maurice & Rycroft, 1986; Nethercott et al, 1983). PETA is a sensitizer as potent as methyl methacrylate (Nethercott, 1978).
    c) The following multifunctional acrylates have produced sensitization reactions in humans:
    1) Dipentaerythritol monohydroxy penta acrylate (DEMPA)
    2) Diethyleneglycol dimethacrylate (DEDMA)
    3) Ethyleneglycol dimethacrylate (EGDMA)
    4) 2-Hydroxyethyl acrylate (HEA)
    5) 2-Hydroxyethyl methacrylate (HEMA)
    6) Hydroxypropyl methacrylate (HPA)
    7) Pentaerythritol triacrylate (PETA)
    8) Polyethyleneglycol dimethacrylate
    9) Polyester acrylate
    10) Tetrahydrofurfuryl methacrylate
    11) Triethylene glycol dimethacrylate (TREGDMA)
    12) Trimethylolpropane triacrylate (TMPTA)
    13) Trimehtylolpropane trimethylacrylate (TMPTMA)
    14) Urethane dimethacrylates
    1) REFERENCES: (Emmett, 1977; Smith, 1977; Nethercott, 1978; Bjorkner et al, 1980; Pedersen et al, 1983; Bjorkner, 1984; Clemmensen, 1985; Lovell et al, 1985; Ranchoff & Taylor, 1985; Andrews & Clary, 1986; Peters & Andersen, 1986; Kokelj et al, 1987; Conde-Salazar et al, 1988; Kanerva et al, 1988; Romaguera et al, 1989; Tobler et al, 1990; Marren et al, 1991; Guerra et al, 1993; Kanerva et al, 1993).
    d) Allergic contact dermatitis has been reported in workers using Loctite(R), Sta-Lok(R) products or exposed to constituents of these products (Mobacken, 1983; Magnusson & Mobacken, 1972; Guerra et al, 1993).
    e) CASE SERIES: A printing company had an outbreak of 13 of 51 employees who developed dermatitis of the hands and face after switching from a solvent-based ink to a water-based ink containing a polyfunctional aziridine hardening agent. This hardening agent contained an excess of TMPTA (Garabrant, 1985).
    f) CASE REPORT: Contact dermatitis, consisting of eczema of the hands and ears and bullous lesions on the fingertips, occurred in a 32-year-old manicurist following occupational exposure to artificial nail products containing acrylates. After giving up her job as a manicurist because of the dermatitis, she began work as a dental nurse. Following occupational exposure to a variety of acrylates resulted in a recurrence of the dermatitis within 4 months. Patch testing with artificial nail products showed positive reactions, within 48 hours, to 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate, ethylene glycol dimethacrylate (EGDMA), 1,6-hexandiol diacrylate, 2-hydroxyethyl acrylate, and triethyleneglycol diacrylate (Kiec-Swierczynska et al, 2013).
    C) HYPERSENSITIVITY REACTION
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: CROSS-SENSITIZATION: In one plant, 5 of 26 workers potentially exposed to the formulation of ultraviolet-cured ink developed eczematous dermatitis. Four of these five workers subsequently had positive patch tests to PETA, TMPTA, and DEMPA. The positive reaction to DEMPA was thought to be a cross-sensitization reaction since none of the employees were exposed to this MFA in the workplace (Emmett, 1977).
    1) Sensitization to hydroxypropyl acrylate (HPA) may have produced cross-sensitization to hydroxypropyl methacrylate and hydroxyethyl methacrylate (HEMA) in one case (Lovell et al, 1985).
    D) NAIL FINDING
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Transient fingernail onycholysis occurred in a woman exposed to 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxylethyl acrylate (2-HEA) and ethyleneglycol dimethacrylate (EGDMA) (Andersen, 1986).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) DERMATITIS CONTACT
    a) GUINEA PIGS: Methacrylated multifunctional acrylic compounds were found to be non-sensitizers or weak sensitizers in guinea pigs (Bjorkner, 1984a). Other sensitizing acrylates in the guinea pig model are ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, 2-Hydroxypropyl acrylate and 2-hydroxyethyl methacrylate (ACGIH, 1986; Van der Walle & Bensink, 1982).
    b) GUINEA PIGS: Some studies involving guinea pigs have found that dimethacrylates are more potent sensitizers than diacrylates (Van der Walle et al, 1983).
    c) GUINEA PIGS: Ranking of dermal sensitization in guinea pigs based on three studies (ranked strongest sensitization scores to weakest sensitization scores):
    1) neopentyl glycol diacrylate (NPGDA)>
    2) tripropylene glycol diacrylate (TPGDA)>
    3) 1,4-butanediol diacrylate (BUDA)>
    4) 1,6-hexanediol diacrylate (HDDA)>
    5) diethylene glycol diacrylate (DEGDA)
    d) Neither triethylene glycol diacrylate (TREGDA) nor tetraethylene glycol diacrylate (TEGDA) produced sensitization in the studies reviewed (Roberts, 1987).
    e) 2-Hydroxypropyl acrylate is a sensitizer in guinea pigs (ACGIH, 1986).
    f) SENSITIZATION STUDY LIMITATIONS: The dose of test compound can influence the result, with high induction dose failing to cause sensitization (overload effect) and low induction dose causing strong sensitization (Roberts, 1987). Some studies reporting no sensitization for various acrylates may be due to the overload effect in dosing.
    2) ALLERGIC REACTION
    a) CROSS-SENSITIZATION (GUINEA PIG): Methyl methacrylate was not a good screen for cross-sensitization in the guinea pig (Van der Walle & Bensink, 1982).
    3) SKIN NECROSIS
    a) DEGDA, HDODA, TREGDA, and TRPGDA may produce severe skin irritation or necrosis following a single exposure (Andrews & Clary, 1986).
    b) HPA is corrosive to skin (ACGIH, 1986). In general, severe irritation or skin necrosis developed with repeated exposure in animals (Andrews & Clary, 1986).
    4) IRRITATION
    a) GUINEA PIG: In guinea pigs it was found that diacrylates are strong irritants and dimethacrylates are weak irritants (HSDB , 2001; Van der Walle et al, 1983).
    b) RABBITS: Diethylene glycol diacrylate was moderately irritating to rabbit skin (HSDB , 2001).

Immunologic

    3.19.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Many multifunctional acrylates cause dermal sensitization. Systemic symptoms associated with patch testing with 2-HEMA, 2-HEA, and EGDMA were reported in one case. Animal studies have shown that multifunctional acrylates are poor immunogens compared to monofunctional acrylates.
    3.19.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) DERMAL SENSITIZATION: Many multifunctional acrylates cause sensitization (Andrews & Clary, 1986; Lovell et al, 1985; Kanerva et al, 1988; Tobler et al, 1990; Kanerva et al, 1993).
    b) Sensitization to dental composite resin products containing multifunctional acrylates occurred in 2 dental nurses and 1 dentist following occupational exposure (HSDB , 2001). Acrylates are considered the fourth most common cause of contact sensitization due to resins.
    c) CASE REPORT: Contact dermatitis, consisting of eczema of the hands and ears and bullous lesions on the fingertips, occurred in a 32-year-old manicurist following occupational exposure to artificial nail products containing acrylates. After giving up her job as a manicurist because of the dermatitis, she began work as a dental nurse. Following occupational exposure to a variety of acrylates resulted in a recurrence of the dermatitis within 4 months. Patch testing with artificial nail products showed positive reactions, within 48 hours, to 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate, ethylene glycol dimethacrylate (EGDMA), 1,6-hexandiol diacrylate, 2-hydroxyethyl acrylate, and triethyleneglycol diacrylate (Kiec-Swierczynska et al, 2013).
    B) ACUTE ALLERGIC REACTION
    1) WITH POISONING/EXPOSURE
    a) Cross-sensitization may occur (Lovell et al, 1985).
    C) SYSTEMIC DISEASE
    1) WITH POISONING/EXPOSURE
    a) SYSTEMIC SENSITIZATION RESPONSE: A woman with a history of fatigue, headache, nausea, vomiting, tongue numbness, and irregular menstruation associated with occupational exposure to 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxyethyl acrylate (2-HEA) and ethyleneglycol dimethacrylate (EGDMA), developed systemic symptoms 6 to 12 hours after patch testing with these chemicals. No dermal hypersensitivity reactions were present (Andersen, 1986).
    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IMMUNOGLOBULINS INCREASED
    a) GUINEA PIG immunization studies demonstrated that it is possible to raise serum antibodies against 4-vinyl pyridine and methyl acrylate but not TMPTA (trimethylolpropane triacrylate).
    b) All three compounds have been associated with induction of contact sensitivity reactions in guinea pigs. These data suggest that MFAs may be poor immunogens compared to the more immunogenic monofunctional acrylates (Bull et al, 1987).

Reproductive

    3.20.1) SUMMARY
    A) No human data were found at the time of this review with the exception of 1 case of menstrual irregularities from exposure to several acrylates. Animal studies at the time of this review did not show conclusive evidence of fetotoxicity or teratogenicity.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) RATS - PETA and GPDA produced equivocal findings at clearly maternally toxic dose levels. A small number of fetuses/litters were found to have uncommon malformations (Andrews & Clary, 1986).
    2) In a subsequent study, PETA produced no fetotoxic or teratogenic effects when the dose given the mothers caused minimal toxic effects (Andrews & Clary, 1986).
    B) LACK OF EFFECT
    1) RATS - TTEGDA, TRPGDA, HDODA, GPTA, and TMPEOTA were found not to be fetotoxic or teratogenic in pregnant rats given a single dose of material during days 6 to 15 of gestation at a clearly maternally toxic dose (Andrews & Clary, 1986).
    2) No teratogenic potential was demonstrated when TMPTA and TMPTMA were screened for activity at doses approaching maternally lethal levels (Andrews & Clary, 1986). The number of fetuses examined in this study was very small.

Carcinogenicity

    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) CONCLUSION - NPGDA, TREGDA, and TTEGDA are potentially weak carcinogens when applied dermally on a chronic basis (Andrews & Clary, 1986).
    a) Five (TMPTA, TMPTMA, HDODA, TRPGDA, and TTEGDMA) of eight MFAs tested for carcinogenicity and chronic dermal toxicity were found to produce no increased incidence of skin or visceral tumors when male MICE (C3H/HeJ) were treated dermally twice weekly for 80 weeks or until tumors were diagnosed or the animals became morbid or died (Andrews & Clary, 1986).
    b) TMPTA, TRPGDA, and HDODA treated ANIMALS received 100 mg/kg.
    c) TTEGDMA and TMPTMA treated ANIMALS received 1,000 mg/kg.
    d) PETA, TREGDA, and TTEGDA showed some potential for carcinogenicity or tumorigenicity (Andrews & Clary).
    2) DePass et al (1985) tested 2-ethylhexyl acrylate (EHA), methylcarbamoyloxyethyl acrylate (MCEA), neopentyl glycol diacrylate (NPGDA), esterdiol-204-diacrylate (EDDA), pentaerythritol tri(tetra)acrylate (PETA), and three acrylated urethane oligomers for potential dermal oncogenicity in C3H/HeJ male MICE. In this model EHA and NPGDA were found to have oncogenic potential.
    B) DERMATITIS
    1) PETA administered at a dose of 100 mg/kg caused slight skin irritation.
    C) LYMPHOMA-LIKE DISORDER
    1) PETA administered at a dose of 100 mg/kg caused lymphomas with spleen or lymph node involvement at the end of the study period in 6 of 50 MICE.
    2) TREGDA given at a dose of 100 mg/kg caused lymphomas in four MICE at the end of the study period.
    D) SKIN HYPERTROPHY
    1) TREGDA given at a dose of 100 mg/kg produced severe skin damage. Six MICE had skin tumors at the end of the study period.
    2) TTEGDA produced severely damaged skin at a dose of 100 mg/kg and an increased incidence of skin tumors.
    3) Of the negative control groups, one MOUSE developed a skin papilloma in both the mineral oil and no-treatment groups.
    E) SKIN CARCINOMA
    1) Of the positive control group in a study, 42 of 50 MICE receiving a estimated dose of 1 mg/kg of benzo(a)pyrene developed squamous cell carcinomas of the skin.
    F) CHRONIC TOXICITY
    1) NPGDA was evaluated for chronic dermal toxicity. A dose of 200 mg/kg applied dermally 3 times weekly for life produced 8 ANIMALS with skin tumors of 40 ANIMALS studied.
    2) PETA was also evaluated at a dose of 120 mg/kg applied dermally 3 times weekly for life. There was no evidence of skin tumorigenic potential by PETA in this study (Andrews & Clary, 1986).

Genotoxicity

    A) SALMONELLA TYPHIMURIUM (AMES) ASSAYS -
    1) Ethyleneglycol diacrylate (EGDA) - negative. strain TA98, TA100, TA1535, TA1537, with or without S9 activation (HSDB , 2001; Cameron et al, 1991)
    2) Ethylene glycol dimethacrylate (EGDMA) - negative. strains TA98, TA100, TA1535, TA1537, with or without S9 activation (Thompson et al, 1991)
    3) Trimethylolpropane triacrylate (TMPTA) - negative. strains TA98, TA100, TA1535, TA1537, TA1538 with or without S9 activation (Thompson et al, 1991)
    4) Trimethylolpropane triacrylate (TMPTA) - weakly positive in TA1535 with S9 activation (Cameron et al, 1991)
    5) Trimethylolpropane trimethacrylate (TMPTMA) - weakly positive in TA1535 with S9 activation (Cameron et al, 1991)
    B) L5178Y TA+/- MOUSE LYMPHOMA ASSAY -
    1) Ethyleneglycol diacrylate (EGDA) - positive with and without S9 (Cameron et al, 1991)
    2) Ethylene glycol dimethacrylate (EGDMA) - positive with S9 (Cameron et al, 1991)
    3) Trimethylolpropane triacrylate (TMPTA) - negative (Thompson et al, 1991)
    4) Trimethylolpropane triacrylate (TMPTA) - positive without S9 (Cameron et al, 1991)
    5) Trimethylolpropane trimethacrylate (TMPTMA) - negative with and without S9 activation (Cameron et al, 1991)
    C) UNSCHEDULED DNA SYNTHESIS/RAT HEPATOCYTES -
    1) TMPTA - negative (Thompson et al, 1991)

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Specific laboratory measures are not indicated.
    B) Patch tests may aid in determining agents responsible for allergic responses and can be used to eliminate exposure to the causative agent.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If respiratory tract irritation is present, monitor chest x-ray.

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 symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    6.3.4) DISPOSITION/EYE EXPOSURE
    6.3.4.1) ADMISSION CRITERIA/EYE
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.1) ADMISSION CRITERIA/DERMAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Monitoring

    A) Specific laboratory measures are not indicated.
    B) Patch tests may aid in determining agents responsible for allergic responses and can be used to eliminate exposure to the causative agent.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    B) ACTIVATED CHARCOAL
    1) There is no data available to suggest that these compounds may or may not be adsorbed to activated charcoal.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive. There is no specific antidote for these compounds.
    2) Exposed individuals should have a careful, thorough medical history and physical examination performed, looking for any abnormalities. Exposure to chemicals with a strong odor often results in such nonspecific symptoms as headache, dizziness, weakness, and nausea.
    B) IRRITATION SYMPTOM
    1) There are no reported cases of MFA ingestions in the literature at this time. These compounds may produce GI irritation.
    2) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    C) GASTROINTESTINAL OBSTRUCTION
    1) MECHANICAL OBSTRUCTION - If these compounds are ingested in the liquid form, they may become cured to a solid form following ingestion. This may present a mechanical obstruction problem.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) BRONCHOSPASM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    B) MONITORING OF PATIENT
    1) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
    2) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.
    C) IRRITATION SYMPTOM
    1) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    2) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).
    a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.
    1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).
    3) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
    4) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.
    D) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    E) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) SKIN ABSORPTION
    1) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    B) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    C) ACUTE ALLERGIC REACTION
    1) Workers who develop hypersensitivity dermal reactions may need to be precluded from further exposure.
    D) ANAPHYLAXIS
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    E) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

    A) ADULT
    1) A 30-year-old woman developed work-related systemic symptoms including fatigue, headache, nausea, vomiting, numbness of the tongue, and irregular menstruation following exposure to ultraviolet curable acrylic compounds including 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, and ethyleneglycol dimethacrylate.
    a) She also developed systemic symptoms associated with patch testing. She refused to be tested in a blind fashion to identify specific agent(s) producing the symptoms (Andersen, 1986).

Range Of Toxicity

Summary

    A) Minimum lethal human exposure is unknown.
    B) Sensitized individuals may react to any subsequent exposure.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) Have not been established.

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) BDA
    1) LD50- (ORAL)RAT:
    a) 3.5 mL/kg (Andrews & Clary, 1986)
    B) DEGDA
    1) LD50- (ORAL)MOUSE:
    a) 550 mg/kg (RTECS, 2001)
    2) LD50- (ORAL)RAT:
    a) 250-5000 mg/kg (Andrews & Clary, 1986; RTECS, 2001)
    C) EGDA
    1) LD50- (ORAL)RAT:
    a) 1.1 mL/kg (Carpenter et al, 1974)
    D) EGDMA
    1) LD50- (ORAL)MOUSE:
    a) 2 g/kg (RTECS, 2001)
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 2800 mg/kg (RTECS, 2001)
    3) LD50- (ORAL)RAT:
    a) 3300 mg/kg (RTECS, 2001)
    E) GPDA
    1) LD50- (ORAL)RAT:
    a) 3.6 g/kg (Andrews & Clary, 1986)
    F) GPTA
    1) LD50- (ORAL)RAT:
    a) > 500-5000 mg/kg (Andrews & Clary, 1986)
    G) HDODA
    1) LD50- (INTRAPERITONEAL)RAT:
    a) 760 mg/kg (RTECS, 2001)
    2) LD50- (ORAL)RAT:
    a) >/= 5 g/kg (Andrews & Clary, 1986; RTECS, 2001)
    H) HPA
    1) LD50- (ORAL)RAT:
    a) 250-500 g/kg (ACGIH, 1986)
    I) PETA
    1) LD50- (ORAL)RAT:
    a) > 500-5000 mg/kg (Andrews & Clary, 1986)
    J) TMPEOTA
    1) LD50- (ORAL)RAT:
    a) > 500-5000 mg/kg (Andrews & Clary, 1986)
    K) TMPTA
    1) LD50- (ORAL)RAT:
    a) > 5 g/kg (Andrews & Clary, 1986)
    L) TMPTMA
    1) LD50- (ORAL)RAT:
    a) 5.7 mL/kg (Carpenter et al, 1974)
    M) TREGDA
    1) LD50- (ORAL)RAT:
    a) > 500-5000 mg/kg (Andrews & Clary, 1986)
    N) TREGDMA
    1) LD50- (ORAL)MOUSE:
    a) 10750 mg/kg (RTECS, 2001)
    2) LD50- (ORAL)RAT:
    a) 10837 mg/kg (RTECS, 2001)
    O) TRPGDA
    1) LD50- (ORAL)RAT:
    a) 6.8 g/kg (Andrews & Clary, 1986)
    P) TTEGDA
    1) LD50- (ORAL)RAT:
    a) > 500-5000 mg/kg (Andrews & Clary, 1986)
    Q) TTEGDMA
    1) LD50- (ORAL)RAT:
    a) > 5000 mg/kg (Andrews & Clary, 1986)

Pharmacology Toxicology

Toxicologic Mechanism

    A) These compounds are potent irritants and sensitizers (Andrews & Clary, 1986).

Physicochemical

Physical Characteristics

    A) 2-HYDROXYPROPYL ACRYLATE: liquid (ACGIH, 1986)

Molecular Weight

    A) DIETHYLENEGLYCOL DIACRYLATE: 214 (Bjorkner, 1984a)
    B) ETHYLENEGLYCOL DIMETHACRYLATE: 198 (Bjorkner, 1984a)
    C) NEOPENTYLGLYCOL DIACRYLATE: 212 (Bjorkner, 1984a)
    D) NEOPENTYLGLYCOL DIMETHACRYLATE: 240 (Bjorkner, 1984a)
    E) OLIGO TRIACRYLATE: 480 (Bjorkner, 1984a)
    F) PENTAERYTHRITOL TETRACRYLATE: 352 (Bjorkner, 1984a)
    G) PENTAERYTHRITOL TRIACRYLATE: 298 (Bjorkner, 1984a)
    H) TETRAETHYLENEGLYCOL DIACRYLATE: 302 (Bjorkner, 1984a)
    I) TETRAETHYLENEGLYCOL DIMETHACRYLATE: 330 (Bjorkner, 1984a)
    J) TRIETHYLENEGLYCOL DIACRYLATE: 258 (Bjorkner, 1984a)
    K) TRIETHYLENEGLYCOL DIMETHACRYLATE: 286 (Bjorkner, 1984a)
    L) TRIPROPYLENEGLYCOL DIACRYLATE: 300 (Bjorkner, 1984a)
    M) 1,4-BUTANEDIOL DIACRYLATE: 198 (Bjorkner, 1984a)
    N) 1,4-BUTANEDIOL DIMETHACRYLATE: 226 (Bjorkner, 1984a)
    O) 1,6-HEXANEDIOL DIACRYLATE: 226 (Bjorkner, 1984a)
    P) 1,6-HEXANEDIOL DIMETHACRYLATE: 254 (Bjorkner, 1984a)
    Q) 2-HYDROXYPROPYL ACRYLATE: 130.14 (ACGIH, 1986a)

References

General Bibliography

    1) ACGIH: Documentation of the Threshold Limit Values, 5th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1986.
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