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EPOXY RESINS AND POLYAMINES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The term 'epoxy' refers to the presence of a three-membered epoxide ring, consisting of two carbon atoms and an oxygen atom. Epoxy resins are formed by condensation of an epoxy compound (usually epichlorohydrin) with an alcohol, phenol or fatty acid to form an ether or ester linkage. The most common type, the 'bisphenol A resin', has a glycidyl ether linkage at each end of the molecule. The resins range in molecular weight from the smallest, diglycidyl ether of bisphenol A (molecular weight 340), to resins of molecular weight 908 and more.
    B) Once an epoxy resin is formed, it is hardened or 'cured' to provide greater stability and strength. Hardeners, such as polyamines, polyamides and anhydrides, react with epoxy groups on the resin to link several molecules.
    C) Reactive diluents may be added to high-molecular-weight epoxy resins to decrease viscosity, in amounts as high as 10 to 15 percent. These consist of low-molecular-weight compounds, such as monoglycidyl ethers, usually containing only one active epoxy group (Anon, 1981). Diluents may be present in epoxy resin products not labeled as containing these substances (Jolanki et al, 1987).
    D) Epoxy resins systems (resin and curing agent) are widely used as adhesives, moulding resins, surface coatings and reinforced plastics. The resins are usually long chain polymers produced by condensation of epichlorhydrin and bisphenol A.

Specific Substances

    A) GENERAL TERMS
    1) Age (allyl glycidyl ether)
    2) Epoxy resin
    3) Resin, epoxy
    CONSTITUENTS OF THE GROUP
    1) Diglycidyl ether of bisphenol A (DGEBA)
    2) Diglycidyl ether of tetrabromo-bisphenol A (Br-DGEBA)
    3) Tetraglycidyl-4,4'-methylene dianiline (TGMDA)
    4) Triglycidyl derivative of p-aminophenol (TGPAP)
    5) o-diglycidylphthalate
    6) 4,4-isopropylidene diphenyl epichlorohydrin
    7) Vinyl cyclohexene diepoxide
    RELATED COMPOUNDS
    1) HARDENERS/AMINES
    2) Triglycidyl isocyanurate (TGIC) AMINES
    3) (3-Amino-methyl-3,5,5-trimethylcyclohexylamine) (IPDA)
    4) Triethylenetetramine (TETA)
    5) Isophorone diamine (IPDA)
    6) Metaphenylenediamine
    7) Xylenediamine
    8) 6 bis (4-amine-3-methyl-cyclohexyl)methane
    9) Diaminodiphenyl sulphone (DDS)
    10) Methylene dianilene
    11) Diaminodiphenylmethane
    12) Boron trifluoride monoethylamine complex
    13) Trimethyl-1,6-hexanediamine
    14) Isophorondiamine
    15) Ethylene diamine (EDA)
    HARDENERS/ANHYDRIDES
    1) Dodecenyl succinic anhydride
    2) Hexahydrophthalic anhydride
    3) phthalic anhydride
    4) trimellitic anhydride
    5) tetrachlorophthalic anhydride
    6) himic anhydride
    7) maleic anhydride
    HARDENERS/ AMIDES
    1) Dicyandiamide
    REACTIVE DILUENTS
    1) Phenyl glycidyl ether
    2) Cresyl glycidyl ether
    3) Butyl glycidyl ether
    4) Allyl glycidyl ether
    5) 1,4-butanediol diglycidyl ether
    6) Neopentyl glycol diglycidyl ether
    7) hexanediol diglycidyl ether

Available Forms Sources

    A) FORMS
    1) Viscosity ranges from low viscosity liquids to solids depending on molecular weight. Solvents added to reduce viscosity may include glycidyl ether (phenyl, allyl or butyl), styrene oxide or styrene epoxide.
    2) Clay like epoxy, which is solid (parts A and B), has not presented a substantial ingestion hazard so far. Conversion to a solid by cross-linking of the polymers is brought about by the curing agent or hardener.
    3) Epoxy resins may penetrate through rubber, polyethylene and PVC gloves. Nitrile and nitrile-butatoluene-rubber gloves gave protection for 48 hours in sensitized workers (Blanken et al, 1987).
    4) Systems requiring external heat for curing commonly use acid anhydride hardeners, whereas exothermic or cold curing systems usually involve polyamines (piperazine, di- or triethylenetriamine). Fumes of both the resin and curing agent are emitted during the curing process.
    B) SOURCES
    1) Small amounts of uncured epoxy resins may be present in plastic medical equipment, such as nasal cannulas (Wright & Fregert, 1983; Toome, 1989), hemodialysis tubing (Mork, 1979), pacemakers (Romaguera & Grimalt, 1981), ostomy bags (Van Ketel et al, 1983; Fregert & Orsmark, 1984; Beck et al, 1985), vinyl hospital identification bands (Fisher, 1985) and insulin pump infusion sets (Boom & Vandriel, 1985).
    2) Uncured epoxy resins may also be found in many metallic objects found in household use, such as twist-off-bottle caps, film cassettes, metal food and cosmetic packages, signboards, and brass hooks and door knobs (Fregert et al, 1980). Other household sources include textile labels (Gregert & Orsmark, 1984), knee patches (Taylor et al, 1983), plastic tool handles (Fischer et al, 1987), and cleaning gloves (Jenkinson & Burrows, 1987).
    3) Trade names include Epon 825(R) (contained in the standard patch test tray) and Epon 828(R).
    C) USES
    1) Epoxy resins systems (resin and curing agent) are widely used as adhesives, moulding resins, surface coatings and reinforced plastics. The resins most commonly used are long chain polymers produced by condensation of epichlorhydrin and bisphenol A.
    2) Non-bisphenol A epoxy resins, such as cycloaliphatic epoxies, are used as transformer encapsulating compounds, electrical equipment insulators, coatings for plastics, metals and paper, and in electron microscopy (Dannaker, 1988).
    3) Triglycidyl isocyanurate (TGIC) is a triepoxy compound used as a cross-linker agent for the polyester resins. It is used in dry paint, a particle paint with no solvent (Rubinstein et al, 2002).

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: Epoxy resins and polyamines are widely used as adhesives, moulding resins, surface coatings and reinforced plastics. Hardeners, such as polyamines, polyamides, and anhydrides, react with epoxy groups on the resin to link several molecules.
    B) TOXICOLOGY: Polyamine hardeners are extremely basic (pH 13 to 14) and have irritant and caustic alkaline properties. These damage the keratin layer of the skin and remove surface lipids, while ingestion may result in severe oral or esophageal burns. Dermal resin systems are among the most important causes of industrial contact dermatitis, and may cause sensitization and/or irritation in up to half of exposed workers.
    C) EPIDEMIOLOGY: Although thousands of exposures occur every year (especially with workers industrially), most of these have only minor or no symptoms.
    D) WITH POISONING/EXPOSURE
    1) DERMAL EXPOSURE: Dermal exposures may result in severe skin irritation, contact dermatitis or, in prolonged or severe exposure, burns. Skin irritation may range from eczema, urticaria, photodermatitis, erythema, persistent itching, severe facial swelling, blistering, and erythema multiforme. Sclerotic skin changes are also possible.
    2) ORAL EXPOSURE: Ingestion of polyamines can cause oral and esophageal burns. Patients may report drooling, dysphagia, substernal or abdominal pain, nausea and vomiting. Dyspnea and stridor could develop if aspiration or upper airway burns develop. Ingestion of methylenedianiline has produced glycosuria. Hypotension, bradycardia, T-wave inversion and ST segment abnormalities were reported in a case of accidental ingestion of methylenedianilene.
    3) INHALATIONAL EXPOSURE: Inhalation of fumes from cured epoxy resins may cause coughing and bronchospasm that may persist for several days. Fumes may also result in periorbital edema, facial pruritus, conjunctivitis, and eyelid contact dermatitis. In addition, nasal pruritus, congestion, sneezing, rhinitis, rhinorrhea, epistaxis, and nasal mucosal erosions have occurred. Organic acid anhydrides may cause an asthmatic-rhinitis syndrome, a flu-like syndrome (cough, fever, myalgias, dyspnea, chills developing 4 to 12 hours after exposure), pulmonary disease-anemia syndrome (cough, dyspnea, hemoptysis, hemolytic anemia, restrictive lung disease, pulmonary infiltrates and rarely respiratory failure) or irritant respiratory effects. Death from asphyxiation has been reported very rarely.
    4) Exposure to methylenedianiline can cause hepatitis. 4,4-methylenedianiline has been linked to bladder cancer. There has been a report of hemolytic anemia after exposure to trimelliticanhydride. Lymphocytopenia and eosinophilia have also been reported after exposure to epoxies.
    0.2.20) REPRODUCTIVE
    A) Estrogens influence the development, growth, and function of the uterus through estrogen receptors alpha and beta. One animal study showed that in utero exposure (not neonatal) of rats to bisphenol A promotes uterine disruption (thinning of the uterine epithelium during estrus) in offspring, probably by influencing expression and distribution of these receptors.

Laboratory Monitoring

    A) Plasma concentrations of these agents are not clinically useful.
    B) No specific lab work is indicated in most cases except as merited by a patient's symptoms (eg, patients with respiratory sequelae may require a chest x-ray, pulse oximetry, or pulmonary function tests).
    C) In patients with exposure to methylenedianiline, monitoring of liver enzymes may be indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Most patients with mild to moderate symptoms may be managed by simple decontamination or removal from exposure and supportive treatment as needed. Treat bronchospasm with inhaled beta2 agonists and systemic corticosteroids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Severe toxicity is extremely rare. However, ingestion of polyamine hardeners that are extremely basic may cause severe alkali burns which may require endoscopy to evaluate the extent of injury. In addition, patients with severe respiratory symptoms from organic acid anhydrides may require intubation.
    C) DECONTAMINATION
    1) INGESTION: Gastrointestinal decontamination is not recommended. Ingestion of most epoxy resins or polyamines has low systemic toxicity. Dilution with water or milk may be first line treatment with those with minimal symptoms. For ingestion of polyamine hardeners, endoscopy and more invasive treatment may be needed.
    2) INHALATION: Move patient to fresh air and monitor for respiratory distress. Administer oxygen and assist ventilation as needed. Bronchospasm may be treated with inhaled beta2 agonists and oral or parenteral corticosteroids.
    3) DERMAL EXPOSURE: Decontaminate skin or mucous membranes immediately with water and a soft sponge. Medical evaluation may be indicated if irritation or pain persists after decontamination.
    4) EYE EXPOSURE: Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation or photophobia persists, evaluation from a healthcare professional may be needed.
    D) AIRWAY MANAGEMENT
    1) Rarely necessary but should be considered in patients with concern for upper airway burns or worsening respiratory distress.
    E) ANTIDOTE
    1) None.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with minimal or no symptoms after inadvertent exposures may be observed at home.
    2) OBSERVATION CRITERIA: Patients who are suicidal or with persistent or worsening symptoms should be sent to a healthcare facility for observation until symptoms are stable or improved.
    3) ADMISSION CRITERIA: Patients with persistent or worsening symptoms despite a period of observation or treatment should be admitted to the hospital, and may require ICU admission if symptoms are especially severe (eg, respiratory distress requiring intubation, severe alkali burns from ingestion). Patients should remain in the hospital until stable and clearly improving.
    4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for any patient with severe effects or in whom the diagnosis is unclear. In addition, patients with esophageal burns may require consultation from gastroenterology for endoscopy or general surgery for operative exploration or repair. Manufacturers may be contacted for MSDS and potentially other respiratory data concerning their products.
    G) PITFALLS
    1) Unfamiliarity with these compounds may result on over-aggressive or a lack of appreciation of potential complications with certain exposures (eg, caustic alkali burns from polyamine hardeners or hepatitis from methylenedianiline).
    H) TOXICOKINETICS
    1) Epoxy resins and polyamines may cause burns to skin within an hour following exposure.
    I) DIFFERENTIAL DIAGNOSIS
    1) Dermatologic irritation can mimic other substances that can cause a contact dermatitis, including poison ivy and metal allergies. Respiratory symptoms may mimic other irritant gases.
    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.
    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) Decontaminate skin or mucous membranes immediately with water and a soft sponge. A physician may need to examine the exposed area if irritation or pain persists after the area is washed.

Range Of Toxicity

    A) TOXICITY: There is very limited data to assess the range of toxicity after acute or chronic human exposure. Following inhalations of a few breaths of a powdered dry-paint (triglycidylisocyanurate, a triepoxy compound), a parcel handler developed eye and nose irritation, a dry cough, and a burning chest discomfort, which improved after eye irrigation and 3 treatments of nebulized albuterol.

Clinical Effects

Summary Of Exposure

    A) USES: Epoxy resins and polyamines are widely used as adhesives, moulding resins, surface coatings and reinforced plastics. Hardeners, such as polyamines, polyamides, and anhydrides, react with epoxy groups on the resin to link several molecules.
    B) TOXICOLOGY: Polyamine hardeners are extremely basic (pH 13 to 14) and have irritant and caustic alkaline properties. These damage the keratin layer of the skin and remove surface lipids, while ingestion may result in severe oral or esophageal burns. Dermal resin systems are among the most important causes of industrial contact dermatitis, and may cause sensitization and/or irritation in up to half of exposed workers.
    C) EPIDEMIOLOGY: Although thousands of exposures occur every year (especially with workers industrially), most of these have only minor or no symptoms.
    D) WITH POISONING/EXPOSURE
    1) DERMAL EXPOSURE: Dermal exposures may result in severe skin irritation, contact dermatitis or, in prolonged or severe exposure, burns. Skin irritation may range from eczema, urticaria, photodermatitis, erythema, persistent itching, severe facial swelling, blistering, and erythema multiforme. Sclerotic skin changes are also possible.
    2) ORAL EXPOSURE: Ingestion of polyamines can cause oral and esophageal burns. Patients may report drooling, dysphagia, substernal or abdominal pain, nausea and vomiting. Dyspnea and stridor could develop if aspiration or upper airway burns develop. Ingestion of methylenedianiline has produced glycosuria. Hypotension, bradycardia, T-wave inversion and ST segment abnormalities were reported in a case of accidental ingestion of methylenedianilene.
    3) INHALATIONAL EXPOSURE: Inhalation of fumes from cured epoxy resins may cause coughing and bronchospasm that may persist for several days. Fumes may also result in periorbital edema, facial pruritus, conjunctivitis, and eyelid contact dermatitis. In addition, nasal pruritus, congestion, sneezing, rhinitis, rhinorrhea, epistaxis, and nasal mucosal erosions have occurred. Organic acid anhydrides may cause an asthmatic-rhinitis syndrome, a flu-like syndrome (cough, fever, myalgias, dyspnea, chills developing 4 to 12 hours after exposure), pulmonary disease-anemia syndrome (cough, dyspnea, hemoptysis, hemolytic anemia, restrictive lung disease, pulmonary infiltrates and rarely respiratory failure) or irritant respiratory effects. Death from asphyxiation has been reported very rarely.
    4) Exposure to methylenedianiline can cause hepatitis. 4,4-methylenedianiline has been linked to bladder cancer. There has been a report of hemolytic anemia after exposure to trimelliticanhydride. Lymphocytopenia and eosinophilia have also been reported after exposure to epoxies.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CONJUNCTIVITIS: Fumes of cured epoxy resins may cause facial pruritus, periorbital edema and conjunctivitis (Laurberg & Christiansen, 1984). Contact with powdered dry-paint resulted in eye irritation which improved after eye irrigation (Rubinstein et al, 2002).
    2) EYELID DERMATITIS: Contact eyelid dermatitis has been reported in individuals sensitized to epoxy resins (Nethercott et al, 1989).
    3) RETINOPATHY: CASE REPORT: Permanent pigmentary retinopathy was reported in a case of accidental ingestion of methylene dianilene. Blurred vision began four days after ingestion, and within three weeks visual acuity was limited to perception of light. Gradual partial visual recovery occurred over several months (Roy et al, 1985).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) EPISTAXIS: Significant epistaxis, rhinitis and nasal mucosal erosions have been reported after exposure to heated epoxy resin containing hexahydrophthalic anhydride. All effects resolved spontaneously after removal from the exposure (Grammer et al, 1993).
    2) SNEEZING: Nasal pruritus, congestion, rhinorrhea and sneezing have been reported in workers exposed to epoxy resins (Moller et al, 1985) Nielson et al, 1992).
    3) SECRETIONS: Frequency of nasal secretions is significantly increased in workers exposed to epoxy resins (Nielsen et al, 1992).
    4) IRRITATION of the nose and eyes were noted in a worker who accidentally inhaled a powdered dry paint (triglycidylisocyanurate). Symptoms resolved over the next 24 hours (Rubinstein et al, 2002).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) BURNS: Ingestion of polyamines results in burns to lips, tongue, oral mucosa or hypopharynx. Presence or absence of burns in the mouth may or may not indicate burns of the esophagus. Pain may occur substernally or abdominally.
    2) DYSPHAGIA may occur with drooling. Spontaneous emesis may aggravate some of these findings.
    3) NO EFFECT: Tissue response to a new epoxy resin-based root canal sealer (AH Plus sealer) was analyzed in dogs following root canal work. No inflammatory cells and no areas of necrosis were observed in any specimen (Leonardo et al, 1999).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Hypotension, bradycardia, T-wave inversion and ST segment abnormalities were reported in a case of accidental ingestion of methylene dianilene (Roy et al, 1985).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) Fumes of cured epoxy resins may cause coughing, asthmatic attacks and bronchospasm for several days beyond exposure. A consistent, reversible increase in airway resistance measured by serial pulmonary function tests has been reported in workers exposed to an amine hardener resin system. This effect was more pronounced in smokers (Tepper, 1962).
    b) Acute, severe, bronchospasm (occupational asthma) may be provoked by inhalation challenge tests to organic anhydrides and result in both immediate and late asthmatic responses (Aleva et al, 1992; Bernstein et al, 1982; Zeiss et al, 1977; Howe et al, 1983; Gallagher et al, 1983; Moller et al, 1985; Ward & Davies, 1982; Nielsen et al, 1989; Taylor, 1991).
    1) It has been noted that patients with occupational asthma reported symptoms begin late in the shift early in the week, but symptoms occur immediately after coming to work at the end of the week. (Venables & Taylor, 1990).
    2) In a study of shipyard painters exposed to epoxy paints, the prevalence of lower respiratory tract symptoms was significantly higher in these workers than in controls. A significant linear relationship was seen between percent decrease in FEV(1) and hours of exposure to epoxy paints (Rempel et al, 1991).
    B) DISORDER OF RESPIRATORY SYSTEM
    1) WITH POISONING/EXPOSURE
    a) TRIMELLITIC ANHYDRIDE: Exposure to trimellitic anhydride dust or fumes can produce any of four distinct clinical syndromes (Pien et al, 1988):
    1) An IGE-mediated asthma-rhinitis syndrome;
    2) A late respiratory systemic syndrome known as the 'TMA flu' occurring 4 to 12 hours after exposure, consisting of cough, dyspnea, myalgia, fever and chills;
    3) Pulmonary disease-anemia syndrome, characterized by cough, dyspnea, hemoptysis, hemolytic anemia, restrictive lung disease, pulmonary infiltrates and occasionally respiratory failure;
    4) Irritant respiratory effects.
    b) Other organic acid anhydrides may cause any of the above four clinical syndromes. Methyl tetrahydrophthalic anhydride has been shown to cause an IgE-mediated response and bronchial hyperreactivity in an occupationally exposed patient (Nielsen et al, 1989).
    C) INJURY DUE TO ASPHYXIATION
    1) WITH POISONING/EXPOSURE
    a) Three workers died of asphyxia after working in a non-ventilated underground water tank with an epoxy resin-based waterproofing paint. A reactive diluent in the epoxy resin glycidyl ether produced fumes that displaced oxygen in the tank, thus causing asphyxia (Gavino et al, 1990).
    D) INCREASED IMMUNOGLOBULIN
    1) WITH POISONING/EXPOSURE
    a) IGE: Strong evidence supports the findings that acid anhydrides may be involved in the IgE antibody-combining site. In a study of tetrachlorophthalic anhydride, it was shown that smokers were at a higher risk of developing a specific IgE-mediated bronchial response (Taylor, 1991).
    E) INJURY OF UPPER RESPIRATORY TRACT
    1) WITH POISONING/EXPOSURE
    a) The epiglottis, vocal cords and trachea may be involved with signs/symptoms of dyspnea, stridor and early shock. Dysphagia may occur with drooling. Spontaneous emesis may aggravate some of these findings.
    b) Inhalation of a powdered dry paint resulted in a dry cough, nasal irritation and burning chest discomfort. No wheezing was noted. treatments of nebulized albuterol resulted in resolution of symptoms (Rubinstein et al, 2002).

Neurologic

    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS EFFECTS
    a) Acute ingestion of epichlorohydrin in laboratory animals has resulted in cyanosis, somnolence, tremor, ataxia, muscular relaxation or paralysis, seizures, respiratory arrest and death (Gosselin et al, 1984; RTECS , 1999).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) STRICTURE OF ESOPHAGUS
    1) WITH POISONING/EXPOSURE
    a) Ingestion of polyamines may result in burns and strictures of the oral pharynx and esophagus. Dysphagia and increased salivation may occur (Rivera et al, 1981). Dysphagia may occur with drooling. Spontaneous vomiting may aggravate some of these findings.

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Exposure to an epoxy resin curing agent, methylenedianiline (MDA), produced toxic hepatitis in 84 people who ate contaminated bread (Kopelman et al, 1966) Kopelman et al, 1966a), in 12 workers using the material in an insulating material manufacturing plant exposed via dermal contact (McGill & Motto, 1974), in 4 of 6 men laying epoxy resin-based flooring (Bastian, 1984) and in a case of accidental one-time ingestion in a 28-year-old man (Roy et al, 1985).
    1) MDA produces a characteristic mixed cholestatic-hepatocellular jaundice with an abrupt onset. Symptoms of severe right-upper-quadrant pain, high fever, chills and rash are followed by jaundice with/or without hepatomegaly. The duration of illness ranges from 1 to 7 weeks. In one case, hepatomegaly developed 6 weeks after ingestion, resolving 2 to 3 weeks later. Liver transaminases remained increased 1 year after the episode (Roy et al, 1985).
    b) CASE REPORT: A 42-year-old man developed acute hepatitis after exposure to 4,4'-methylenedianiline (MDA) after starting a new job processing insulation of polyurethane pipes. He presented with a 10-day history of generalized malaise and mild epigastric discomfort. He also had icterus, stool discoloration, and dark-colored urine that started a day before presentation. Laboratory results revealed mild normocytic anemia (Hb 12.5 g/dL), marked eosinophilia (2500/mcL), elevated liver enzymes (AST 1136 Units/L, ALT 1306 Units/L, and ALP 242 Units/L), markedly elevated serum bilirubin concentrations (total bilirubin 22 mg/dL, direct bilirubin 14 mg/dL), prolonged INR 1.22, decreased serum albumin concentrations (3 g/dL). Hepatomegaly and a moderate quantity of ascetic fluid in the perihepatic space were observed during abdominal imaging. A liver biopsy on day 7 revealed diffuse cellular infiltration, marked cholestasis and moderate fibrosis, consistent with the diagnosis of toxic hepatitis. Following supportive therapy, including treatment with methylprednisolone 32 mg daily (gradually tapered), his condition rapidly improved. He was discharged on day 24 (Giouleme et al, 2011).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GALL BLADDER DISORDER
    a) RATS: Acute toxicity of methylene dianiline (MDA) on the hepatobiliary function in rats was described. MDA rapidly diminished bile flow and altered the secretion of bile constituents and was highly injurious to biliary epithelial cells (Kanz et al, 1992). Humans may develop jaundice, cholangitis with cholestasis, or toxic hepatitis.

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMOLYTIC ANEMIA
    1) WITH POISONING/EXPOSURE
    a) Hemolytic anemia may occur in patients exposed to fumes containing TRIMELLITIC ANHYDRIDE. Spontaneous remission may occur within several weeks (Rivera et al, 1981).
    B) LEUKOPENIA
    1) WITH POISONING/EXPOSURE
    a) Epoxy resins were identified as a risk factor for lymphocytopenia among pattern and model makers with occupational exposure (odds ratio, 1.94; 95 percent confidence interval, 1.02 to 3.07). Duration of exposure or percentage of time exposed were not clearly associated with these findings (Demers et al, 1994).
    C) EOSINOPHIL COUNT RAISED
    1) WITH POISONING/EXPOSURE
    a) A case report of occupational-induced asthma by diamine groups of a hardener was accompanied by significant eosinophilia in peripheral blood and in bronchoalveolar lavage fluid (Aleva et al, 1992).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) SKIN FINDING
    1) WITH POISONING/EXPOSURE
    a) Epoxy resin exposure may produce severe burns to skin, dermatitis, lacrimation or sneezing. Some dye bases (such as metaphenylenediamine), after oxidation, may cause skin to turn yellow. Cutaneous amine reactions include chemical burns, erythema, persistent itching, severe facial swelling, and blistering with leaking of serous fluid, crusting and scaling (Cohen, 1985).
    B) SYSTEMIC SCLEROSIS
    1) WITH POISONING/EXPOSURE
    a) Widespread sclerotic skin changes, erythema, brownish pigmentation and telangiectasia were reported in two workers engaged in the polymerization of epoxy resins with an amine hardener (Yamakage et al, 1980). A 17-year follow-up of these two workers showed systemic manifestations and indurated sclerotic skin changes that disappeared within 5 years. No internal organ involvement developed during the period of follow-up (Ishikawa et al, 1995).
    C) ECZEMA
    1) WITH POISONING/EXPOSURE
    a) Acute and chronic eczema, described as an itchy erythematous papular vesicular dermatitis, has been reported after occupational contact with epoxy resins and hardeners (Xuemin et al, 1992).
    D) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Occupational exposure to epoxy resins may cause irritant dermatitis, believed to be related to the alkaline hardeners (Jolanki et al, 1987a).
    b) CASE SERIES: Five patients (age range: 34 to 71 years) developed allergic contact dermatitis after exposure to epoxy resin and later developed persistent photosensitivity either simultaneously (2 patients) or 5 months to 12 years (3 patients) post-exposure. All patients had positive patch testing to epoxy resin. Photosensitivity continued for at least 2 years after diagnosis in all patients. The mechanism to explain the relationship between epoxy resins and photosensitivity remains unclear (Kwok et al, 2013).
    E) URTICARIA
    1) WITH POISONING/EXPOSURE
    a) Contact urticaria has been reported after occupational exposure (Jolanki et al, 1987a).
    F) PHOTOSENSITIVITY
    1) WITH POISONING/EXPOSURE
    a) Persistent light reactive photoallergic contact dermatitis was described in eight outdoor pipe repair workers using an epoxy resin (Allen & Kaidbey, 1979).
    b) CASE SERIES: Five patients (age range: 34 to 71 years) developed allergic contact dermatitis after exposure to epoxy resin and later developed persistent photosensitivity either simultaneously (2 patients) or 5 months to 12 years (3 patients) post-exposure. All patients had positive patch testing to epoxy resin. Photosensitivity continued for at least 2 years after diagnosis in all patients. The mechanism to explain the relationship between epoxy resins and photosensitivity remains unclear (Kwok et al, 2013).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) GLYCOSURIA
    1) WITH POISONING/EXPOSURE
    a) Glycosuria has been reported after ingestion of methylenedianilene (Roy et al, 1985).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ALLERGIC CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Contact dermatitis is a common occupational illness in workers exposed to epoxy resins (Leow et al, 1995; Kiec-Swierczynska, 1995). According to studies, epoxy resins are the third most common cause of occupational allergic contact dermatitis (Ortiz-Frutos et al, 1993).
    b) Although most cases of sensitization occur after exposure to uncured resin, cured resins in the form of sawdust have also been reported to cause dermatitis (Suhonen, 1983; Ward & Davies, 1982). Some hardeners, such as triglycidyl isocyanurate (TGIC), have also been reported to cause contact dermatitis (Foulds & Koh, 1992).
    c) Sources of epoxy resins that resulted in allergic contact dermatitis in 23 patients were: epoxy resin adhesives, epoxy resin grouting agent and miscellaneous sources, including fibre/laminating paper, the manufacture of tennis rackets, printing inks used in electronics and epoxy paints (Leow et al, 1995).
    d) Allergenicity depends on the molecular weight of the resin and the amount of free oligomer in the 'cured' product. The oligomer with a molecular weight of 340 is a potent human sensitizer, and may be present in trace amounts in products containing mainly larger molecules, resulting in sensitization (Jolanki et al, 1987a). The oligomer with a molecular weight of 624 is an animal sensitizer only, and those with molecular weights of 908 and more are nonsensitizing (Anon, 1981).
    e) PREVALENCE
    1) Among 20,808 consecutive dermatitis patients patch tested for reaction to epoxy resin, 275 (1.3%) tested positive. Specific conditions reported among the 275 allergic patients included atopic dermatitis in 10.1%, hand dermatitis in 43.3%, and facial dermatitis in 34.7% (Bangsgaard et al, 2012).
    2) Of 486 patients diagnosed with occupational dermatitis, 99 (20%) were found sensitive to at least 1 of 7 epoxy allergens, as shown by patch testing; 52% of patients were sensitive only to resin; 22% , to resin and hardener; and 16%, only to hardener (Kiec-Swierczynska, 1995).
    3) The prevalence in one epoxy resin plant involving 228 workers was 4.4% (Prens et al, 1986), and in another plant involving 135 workers was 18% (van Putten et al, 1984).
    f) ONSET
    1) Based on a questionnaire response from 95 patients in contact with epoxy resins at work who had a positive reaction to epoxy resin patch testing, the onset of dermatitis after starting work ranged from less than 3 months in 34 patients (36.6 %) to greater than 5 years in 15 (15.8%) patients (Bangsgaard et al, 2012).
    2) According to one study, the average exposure time before onset of allergic contact dermatitis was 18.4 months (range, 1 month to 3 years) in 23 patients (Leow et al, 1995).
    3) Allergic contact dermatitis may result after only one exposure to strong allergens such as diglycidyl ether of bisphenol A epoxy resin.
    g) CASE REPORTS
    1) Allergic contact dermatitis was reported in a chemical industrial worker after contact with ethylenediamine (EDA), contained in epoxy hardeners. The dermatitis was considered a direct effect of EDA sensitization (Chieregato et al, 1994).
    2) Erythema multiforme, presenting as an intense pruritic papular eruption, has been linked with an allergic contact dermatitis due to an epoxy resin and hardener (Whitfeld & Rivers, 1991).
    3) Hand and arm exudative eczema and purpuric eruptions have been described (Laurberg & Christiansen, 1984).
    B) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) Specific IgE and IgG antibodies against tetrachlorophthalic acid and human albumin conjugate were found in seven patients with tetrachlorophthalic acid-induced asthma (Taylor, 1991).
    C) RHINITIS
    1) WITH POISONING/EXPOSURE
    a) One report suggests that an immunologic mechanism, with increased titers of IgG and IgE against hexahydrophthalyl-human serum albumin, was responsible for the rhinitis, epistaxis and nasal mucosal erosions that occurred in six workers who were exposed to heated epoxy resin containing hexahydrophthalic anhydride (HHPA). Other workers with similar exposures to HHPA, but with no or minimal antibodies, did not have these effects. (Grammer et al, 1993).
    D) INCREASED IMMUNOGLOBULIN
    1) IgG against trimellitic anhydride human serum albumin complex has been documented in exposed workers (Gerhardsson et al, 1993).

Reproductive

    3.20.1) SUMMARY
    A) Estrogens influence the development, growth, and function of the uterus through estrogen receptors alpha and beta. One animal study showed that in utero exposure (not neonatal) of rats to bisphenol A promotes uterine disruption (thinning of the uterine epithelium during estrus) in offspring, probably by influencing expression and distribution of these receptors.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Estrogens influence the development, growth, and function of the uterus through estrogen receptors alpha and beta. One animal study showed that in utero exposure (not neonatal) of rats to bisphenol A promotes uterine disruption (thinning of the uterine epithelium during estrus) in offspring, probably by influencing expression and distribution of these receptors (Schonfelder et al, 2004).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) BLADDER CARCINOMA
    1) CASE SERIES - Long-term (> 20 years) follow-up of 10 workers exposed to MDA showed one worker contracted transitional cell bladder cancer. Other studies have shown similar bladder cancers in people exposed to MDA, which is structurally related to known bladder carcinogens such as benzidine (Liss & Guirguis, 1994).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations of these agents are not clinically useful.
    B) No specific lab work is indicated in most cases except as merited by a patient's symptoms (eg, patients with respiratory sequelae may require a chest x-ray, pulse oximetry, or pulmonary function tests).
    C) In patients with exposure to methylenedianiline, monitoring of liver enzymes may be indicated.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor liver enzymes in patients exposed to methylenedianiline.

Methods

    A) OTHER
    1) The low-molecular-weight diglycidal ether of bisphenol A is part of the standard contact dermatitis patch test series. Manufacturers should be contacted regarding patch test materials for other types of epoxy resins.

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 persistent or worsening symptoms despite a period of observation or treatment should be admitted to the hospital, and may require ICU admission if symptoms are especially severe (eg, respiratory distress requiring intubation, severe alkali burns from ingestion). Patients should remain in the hospital until stable and clearly improving.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients with minimal or no symptoms after inadvertent exposures may be observed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a medical toxicologist or poison center for any patient with severe effects or in whom the diagnosis is unclear. In addition, patients with esophageal burns may require consultation from gastroenterology for endoscopy or general surgery for operative exploration or repair. Manufacturers may be contacted for MSDS and potentially other respiratory data concerning their products.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients who are suicidal or with persistent or worsening symptoms should be sent to a healthcare facility for observation until symptoms are stable or improved.

Monitoring

    A) Plasma concentrations of these agents are not clinically useful.
    B) No specific lab work is indicated in most cases except as merited by a patient's symptoms (eg, patients with respiratory sequelae may require a chest x-ray, pulse oximetry, or pulmonary function tests).
    C) In patients with exposure to methylenedianiline, monitoring of liver enzymes may be indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital gastrointestinal decontamination is not recommended. Ingestion of most epoxy resins or polyamines has low systemic toxicity. Dilution with a small amount of milk or water is reasonable if performed shortly after exposure.
    B) 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).
    C) DERMAL EXPOSURE
    1) Decontaminate skin or mucous membranes immediately with water and a soft sponge. Medical evaluation may be indicated if irritation or pain persists after decontamination.
    D) EYE EXPOSURE
    1) Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation or photophobia persists, evaluation from a healthcare professional may be needed.
    E) INHALATION EXPOSURE
    1) Move patient to fresh air and monitor for respiratory distress. Administer oxygen and assist ventilation as needed. Bronchospasm may be treated with inhaled beta2 agonists and oral or parenteral corticosteroids.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY: Gastrointestinal decontamination is not recommended. Ingestion of most epoxy resins or polyamines has low systemic toxicity. Dilution with water or milk may be first line treatment with those with minimal symptoms. For ingestion of polyamine hardeners, endoscopy and more invasive treatment may be needed.
    B) 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).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Most patients with mild to moderate symptoms may be managed by simple decontamination or removal from exposure and supportive treatment as needed. Treat bronchospasm with inhaled beta2 agonists and systemic corticosteroids.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Severe toxicity is extremely rare. However, ingestion of polyamine hardeners that are extremely basic may cause severe alkali burns which may require endoscopy to evaluate the extent of injury. In addition, patients with severe respiratory symptoms from organic acid anhydrides may require intubation.
    B) MONITORING OF PATIENT
    1) Plasma concentrations of these agents are not clinically useful.
    2) No specific lab work is indicated in most cases except as merited by a patient's symptoms (eg, patients with respiratory sequelae may require a chest x-ray, pulse oximetry, or pulmonary function tests).
    3) In patients with exposure to methylenedianiline, monitoring of liver enzymes may be indicated.
    C) ENDOSCOPIC PROCEDURE
    1) There is little information regarding the use of endoscopy, corticosteroids or surgery in the setting of concentrated epoxy resins and polyamine ingestion. The following information is derived from experience with other corrosives.
    2) SUMMARY: Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated.
    3) INDICATIONS: Endoscopy should be performed in adults with a history of deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after unintentional ingestion (Crain et al, 1984). Endoscopy should also be performed in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion (Gaudreault et al, 1983; Nuutinen et al, 1994). Children and adults who are asymptomatic after accidental ingestion do not require endoscopy (Gupta et al, 2001; Lamireau et al, 2001; Gorman et al, 1992).
    4) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.
    a) REFERENCES: (Dogan et al, 2006; Symbas et al, 1983; Crain et al, 1984a; Gaudreault et al, 1983a; Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992)
    5) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):
    a) Advancing across the cricopharynx under direct vision
    b) Gently advancing with minimal air insufflation
    c) Never retroverting or retroflexing the endoscope
    d) Using a pediatric flexible endoscope
    e) Using extreme caution in advancing beyond burn lesion areas
    f) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).
    6) GRADING
    a) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding, and perforation is related to the severity of the initial burn (Zargar et al, 1991):
    b) Grade 0 - Normal examination
    c) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
    d) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
    e) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
    f) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation or gastrointestinal bleeding may occur.
    g) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.
    7) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
    8) SCINTIGRAPHY - Scans utilizing radioisotope labelled sucralfate (technetium 99m) were performed in 22 patients with caustic ingestion and compared with endoscopy for the detection of esophageal burns. Two patients had minimal residual isotope activity on scanning but normal endoscopy and two patients had normal activity on scan but very mild erythema on endoscopy. Overall the radiolabeled sucralfate scan had a sensitivity of 100%, specificity of 81%, positive predictive value of 84% and negative predictive value of 100% for detecting clinically significant burns in this population (Millar et al, 2001). This may represent an alternative to endoscopy, particularly in young children, as no sedation is required for this procedure. Further study is required.
    9) MINIPROBE ULTRASONOGRAPHY - was performed in 11 patients with corrosive ingestion . Findings were categorized as grade 0 (distinct muscular layers without thickening, grade I (distinct muscular layers with thickening), grade II (obscured muscular layers with indistinct margins) and grade III (muscular layers that could not be differentiated). Findings were further categorized as to whether the worst appearing image involved part of the circumference (type a) or the whole circumference (type b). Strictures did not develop in patients with grade 0 (5 patients) or grade I (4 patients) lesions. Transient stricture formation developed in the only patient with grade IIa lesions, and stricture requiring repeated dilatation developed in the only patient with grade IIIb lesions (Kamijo et al, 2004).
    D) CORTICOSTEROID
    1) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
    2) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
    3) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
    4) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
    5) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
    6) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
    7) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
    8) STUDIES
    a) ANIMAL
    1) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973a).
    2) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
    3) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).
    b) HUMAN
    1) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
    2) META ANALYSIS
    a) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
    b) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
    c) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).
    3) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
    4) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
    5) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).
    a) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
    b) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
    c) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
    d) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
    e) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).
    6) ADVERSE EFFECTS
    a) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).
    E) SURGICAL PROCEDURE
    1) SUMMARY: Initially if severe esophageal burns are found a string may be placed in the stomach to facilitate later dilation. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. Dilation is indicated after 2 to 4 weeks if strictures are confirmed. If dilation is unsuccessful colonic intraposition or gastric tube placement may be needed. Early laparotomy should be considered in patients with evidence of severe esophageal or gastric burns on endoscopy.
    2) STRING - If a second degree or circumferential burn of the esophagus is found a string may be placed in the stomach to avoid false channel and to provide a guide for later dilation procedures (Gandhi et al, 1989).
    3) STENT - The insertion of a specialized nasogastric tube or stent immediately after endoscopically proven deep circumferential burns is preferred by some surgeons to prevent stricture formation (Mills et al, 1978; (Wijburg et al, 1985; Coln & Chang, 1986).
    a) STUDY - In a study of 11 children with deep circumferential esophageal burns after caustic ingestion, insertion of a silicone rubber nasogastric tube for 5 to 6 weeks without steroids or antibiotics was associated with stricture formation in only one case (Wijburg et al, 1989).
    4) DILATION - Dilation should be performed at 1 to 4 week intervals when stricture is present(Gundogdu et al, 1992). Repeated dilation may be required over many months to years in some patients. Successful dilation of gastric antral strictures has also been reported (Hogan & Polter, 1986; Treem et al, 1987).
    5) COLONIC REPLACEMENT - Intraposition of colon may be necessary if dilation fails to provide an adequate sized esophagus (Chiene et al, 1974; Little et al, 1988; Huy & Celerier, 1988).
    6) LAPAROTOMY/LAPAROSCOPY - Several authors advocate laparotomy or laparoscopy in patients with endoscopic evidence of severe esophageal or gastric burns to evaluate for the presence of transmural gastric or esophageal necrosis (Cattan et al, 2000; Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993).
    a) STUDY - In a retrospective study of patients with extensive transmural esophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (esophagoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).

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) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    2) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    3) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three 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 nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    4) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    5) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    B) 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) DERMAL DECONTAMINATION
    1) 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) CONTRAINDICATED TREATMENT
    1) Do NOT cover skin or mucous membranes.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

    A) ADULT
    1) ROUTE OF EXPOSURE
    a) A 28-year-old man accidentally swallowed several mouthfuls of a solution of methylene dianilene in potassium carbonate and gamma butyrolactone. Initial signs and symptoms included coma, areflexia, pallor, miosis, Cheyne-Stokes respiration, bradycardia, hypotension, T-wave inversion and ST abnormalities. He was alert after two hours and vomited. By the second day, serum transaminases and bilirubin were increased. On the fourth day a pigmentory toxic retinopathy developed, which resolved incompletely within a few months. Other complications included hematuria, glycosuria, mild sensory peripheral neuropathy and erythema multiforme. Pruritus and hepatomegaly developed six weeks after ingestion, and persisted for two to three weeks. Liver function tests remained abnormal one year after the episode (Roy et al, 1985).

Range Of Toxicity

Summary

    A) TOXICITY: There is very limited data to assess the range of toxicity after acute or chronic human exposure. Following inhalations of a few breaths of a powdered dry-paint (triglycidylisocyanurate, a triepoxy compound), a parcel handler developed eye and nose irritation, a dry cough, and a burning chest discomfort, which improved after eye irrigation and 3 treatments of nebulized albuterol.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) Limited data are available on human acute toxicity.
    B) ANIMAL DATA
    1) Epichlorohydrin administered daily for 10 to 20 days at concentrations of 0.1 milliliter/kilogram killed all mice in a sample population. Application to the skin of 0.5 milliliter/kilogram daily killed all of a group of rats in 4 days. For mice, 8300 parts per million in atmosphere for 30 minutes was fatal (Gosselin et al, 1984).
    2) A concentration of 250 parts per million for 8 hours was lethal to 50 percent of rats in an LC50 study (RTECS , 2002).

Maximum Tolerated Exposure

    A) ACUTE
    1) CASE REPORT: Following inhalation of a few breaths of a powdered dry-paint (triglycidylisocyanurate, a triepoxy compound), a parcel handler developed eye and nose irritation, a dry cough, and a burning chest discomfort. Eye irrigation and 3 treatments with nebulized albuterol resulted in symptomatic improvement of eye and chest pain (Rubinstein et al, 2002).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) DIETHYLENETRIAMINE
    1) LD50- (ORAL)RAT:
    a) 1080 mg/kg (RTECS , 2002a)
    B) EPICHLOROHYDRIN
    1) LD50- (ORAL)RAT:
    a) 90 mg/kg (RTECS , 2002a)

Pharmacology Toxicology

Toxicologic Mechanism

    A) CAUSTIC - The polyamine hardeners are extremely basic (pH 13 to 14) and have volatile and caustic alkaline properties. These damage the keratin layer of the skin and remove surface lipids (Kanerva et al, 1994). Ingestion may thus result in severe skin or esophageal burns.
    B) DERMAL - Dermal resin systems are among the most important causes of industrial contact dermatitis and may cause irritation and/or sensitization in a high percentage of exposed workers. Epoxy resins are well-known sensitizers, and a single exposure may induce sensitization (Kanerva et al, 1994). Positive patch-tests to epoxy resins can be as high as 50 percent in some occupational settings (Blanken et al, 1987). The main source of epoxy sensitization is reported to be paints and surface coatings (Jolanki et al, 1987).

Physicochemical

Molecular Weight

    A) varies

References

General Bibliography

    1) Aceto T Jr, Terplan K, & Fiore RR: Chemical burns of the esophagus in children and glucocorticoid therapy. J Med 1970; 1:101-109.
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