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DIMETHYL SULFOXIDE (DMSO)

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dimethyl sulfoxide is an industrial solvent. It is a very hygroscopic liquid, and is prepared by air-oxidation of dimethyl sulfide in the presence of nitrogen oxides.

Specific Substances

    1) DIMETHYL SULFOXIDE
    2) DMSO
    3) Methyl sulphoxide
    4) NSC-763
    5) SQ-9453
    6) Molecular Formula: C2-H6-OS
    7) NIOSH/RTECS PV 6210000
    8) CAS 67-68-5
    1.2.1) MOLECULAR FORMULA
    1) C2-H6-O-S

Available Forms Sources

    A) FORMS
    1) Dimethyl sulfoxide is available as 50% w/w aqueous solution for intravesical instillation (Prod Info RIMSO-50(R) intravesical irrigant, 2012). It is also available as 99% topical solution (Prod Info Cryoserv(TM), 2003).
    B) SOURCES
    1) Dimethyl sulfoxide is an industrial solvent. It is a very hygroscopic liquid, and is prepared by air-oxidation of dimethyl sulfide in the presence of nitrogen oxides (Budavari, 1996; S Sweetman , 2001).
    C) USES
    1) MEDICAL USES
    a) Dimethyl sulfoxide (DMSO) is indicated for the symptomatic relief of interstitial cystitis (Prod Info RIMSO-50(R) intravesical irrigant, 2012).
    b) Dimethylsulfoxide is also used for extravasation caused by amsacrine, cisplatin, dactinomycin, mitomycin, and MitoXANTRONE (Gippsland Oncology Nurses Group, 2010; Wengstrom et al, 2008). Limited availability in the US (Schulmeister, 2011).
    2) INDUSTRIAL USES
    a) Dimethyl sulfoxide is used as a solvent for acetylene, sulfur dioxide and other gases; in organic reactions; as antifreeze or hydraulic fluid when mixed with water; as a solvent for Orlon; and as a paint and varnish remover. It dissolves some hydrocarbons more than others (Budavari, 1996).
    b) It is also used as a metal-complexing agent; as a solvent for polymerization and cyanide reactions; as an analytical reagent; for spinning polyacrylonitrile and other synthetic fibers; in industrial cleaners, pesticides, and paint stripping; and in hydraulic fluids (Lewis, 1993).
    c) Products intended for industrial use may be contaminated with trace amounts of heavy metals, especially lead.
    3) VETERINARY USES
    a) A 90% w/w gel is available for topical treatment of muscle and joint pains in dogs and horses. It is also available (60% w/v) mixed with fluocinolone acetonide as a otic preparation for treatment of chronic otitis in dogs (Luery et al, 1984).

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 THERAPEUTIC USE
    1) DMSO has shown very few toxic symptoms in humans. The most common are nausea, skin rashes, headache, and an unusual garlic-onion-oyster smell in body and breath.
    2) DMSO is a skin, eye, and respiratory tract irritant. It may cause skin irritation and reddening if spilled on clothing and allowed to remain. DMSO readily penetrates the skin and may carry other dissolved chemicals into the body.
    3) DMSO may cause urticaria and, rarely, anaphylaxis.
    4) DMSO is an experimental teratogen and also causes other reproductive effects in experimental animals. It is also a questionable carcinogen with experimental tumorigenic data.
    0.2.4) HEENT
    A) WITH THERAPEUTIC USE
    1) Dry throat, mouth, and nasal passages are possible with prolonged use.
    B) WITH POISONING/EXPOSURE
    1) Transient photophobia and color vision disturbances have been reported.
    2) ANIMAL STUDIES - The lenticular changes causing myopia seen in animals following chronic use have not yet been reported in humans.
    0.2.6) RESPIRATORY
    A) WITH THERAPEUTIC USE
    1) The unusual oyster breath is a common finding. Dyspnea and increased symptoms of bronchial asthma are possible.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Headache, dizziness, and sedation have been seen.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, diarrhea, anorexia and constipation may occur.
    0.2.9) HEPATIC
    A) WITH THERAPEUTIC USE
    1) Elevated liver enzymes have been reported, and two questionable cases of liver toxicity have been reported.
    0.2.10) GENITOURINARY
    A) WITH THERAPEUTIC USE
    1) A dose dependent hematuria is possible.
    0.2.13) HEMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Possible eosinophilia has been reported, and when given IV, hemolysis and increased serum osmolality has been reported.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Stinging and burning of the skin as well as rashes and vesicles have been seen. A heat reaction may occur if administered on wet skin. Systemic contact dermatitis has occurred from intravesical administration.
    0.2.19) IMMUNOLOGIC
    A) WITH THERAPEUTIC USE
    1) DMSO releases histamine from mast cells.
    0.2.20) REPRODUCTIVE
    A) Data for humans are lacking. Teratogenic effects have been seen in animals. permatozoa of honey bees frozen with DMSO as the cryoprotectant produced total sterility in 3% of the female progeny. Total sterility is very rare in honey bees.

Laboratory Monitoring

    A) Although analysis is available from special laboratories, the levels have little clinical meaning.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Emesis should NOT be induced, since this is a solvent and aspiration is possible. If large amounts have been ingested, consider lavage after intubation.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) SUPPORTIVE CARE - Monitor the patient's liver function, kidney function, hemoglobin, and platelet function.
    D) PERITONEAL DIALYSIS was tried in one case report (Yellowlees et al, 1980) and deemed not effective.
    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) Rashes are common reactions that may need physical examination.
    3) DMSO carries other substances through the skin. Take a careful history as to what other chemicals might be involved, and observe for toxic effect from these chemicals.
    0.4.6) PARENTERAL EXPOSURE
    A) Too rapid administration or too concentrated a solution will cause hemolysis and subsequent hematuria. Monitor for this when administering DMSO intravenously.

Range Of Toxicity

    A) There are no therapeutic or toxic blood levels established.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) DMSO has shown very few toxic symptoms in humans. The most common are nausea, skin rashes, headache, and an unusual garlic-onion-oyster smell in body and breath.
    2) DMSO is a skin, eye, and respiratory tract irritant. It may cause skin irritation and reddening if spilled on clothing and allowed to remain. DMSO readily penetrates the skin and may carry other dissolved chemicals into the body.
    3) DMSO may cause urticaria and, rarely, anaphylaxis.
    4) DMSO is an experimental teratogen and also causes other reproductive effects in experimental animals. It is also a questionable carcinogen with experimental tumorigenic data.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) HYPOTHERMIA - Experimental animals develop hypothermia prior to death following massive single doses (Gosselin et al, 1984).

Heent

    3.4.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Dry throat, mouth, and nasal passages are possible with prolonged use.
    B) WITH POISONING/EXPOSURE
    1) Transient photophobia and color vision disturbances have been reported.
    2) ANIMAL STUDIES - The lenticular changes causing myopia seen in animals following chronic use have not yet been reported in humans.
    3.4.2) HEAD
    A) WITH THERAPEUTIC USE
    1) FLUSHING of the face was seen in a patient who received an infusion of 120 mL of 10% DMSO (O'Donnell et al, 1981).
    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) ANIMAL STUDIES
    a) CATARACT FORMATION - Topically and orally administered DMSO has been said to cause cataracts in dogs and rabbits. DMSO eye drops did not cause this affect in rabbits (Rubin & Barnett, 1967; Smith et al, 1967; Wood et al, 1967).
    b) DMSO-induced (dose related) cataracts is fairly similar for all animal species (Olson, 1982).
    c) CONJUNCTIVAL ERYTHEMA - Single intravitreal injections of a 1%, 10%, 50%, and 100% DMSO in rabbits produced transient, but no permanent toxic effects to lens or retina. The most noticeable affects were conjunctiva erythema and focal retinal edema (Silverman & Yoshizumi, 1983).
    d) There have been reports from animal studies that lenticular changes involving the refractive index of the lens and causing myopia and hyperopia have occurred. This effect has not been seen in man or other primates. The report mentions conjunctival irritation, but this may be due to touch contamination, not a systemic reaction (Brobyn, 1975).
    2) LENS CHANGES - No adverse ocular effects were seen in 9 of 12 patients receiving topical DMSO 70% solution applied to the hands three times daily for 12 weeks. Mild nuclear lens changes were seen in one patient. These changes were not similar to those seen in animal studies (Shirley et al, 1989).
    B) WITH POISONING/EXPOSURE
    1) PHOTOPHOBIA - Transient photophobia and disturbances of color vision have been reported.
    3.4.6) THROAT
    A) WITH THERAPEUTIC USE
    1) DRY THROAT - Chronic or acute symptoms include dry throat, mouth, and nasal passages (Brobyn, 1975).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) VASODILATATION
    1) WITH THERAPEUTIC USE
    a) DMSO typically causes vasodilation.
    B) TACHYARRHYTHMIA
    1) WITH THERAPEUTIC USE
    a) Tachycardia was noted in a patient who was given 120 mL of a 10% DMSO solution IV. The sinus tachycardia lasted about 30 minutes (O'Donnell et al, 1981).
    C) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension was noted in a patient who received 120 mL of a 10% DMSO solution IV (O'Donnell et al, 1981).
    D) CHEST PAIN
    1) WITH THERAPEUTIC USE
    a) Chest pains have been reported after use (Klingman, 1965).

Respiratory

    3.6.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) The unusual oyster breath is a common finding. Dyspnea and increased symptoms of bronchial asthma are possible.
    3.6.2) CLINICAL EFFECTS
    A) SMELL OF BREATH - FINDING
    1) WITH THERAPEUTIC USE
    a) There is a general garlic-onion-oyster odor to the breath which appears within minutes of an IV or topical dose, due to a sulfone metabolite (Luery et al, 1984).
    B) DYSPNEA
    1) WITH THERAPEUTIC USE
    a) There is a report of dyspnea and worsening of bronchial asthma symptoms (Brown, 1982).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Headache, dizziness, and sedation have been seen.
    3.7.2) CLINICAL EFFECTS
    A) CEREBRAL EDEMA
    1) WITH THERAPEUTIC USE
    a) There is some evidence that DMSO will decrease cerebral edema (Sherman & Easton, 1980).
    B) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Dizziness and sedation have been seen (Council Report, 1982).
    C) PSYCHOMOTOR AGITATION
    1) WITH THERAPEUTIC USE
    a) Agitation was seen in a patient who received an infusion of 120 mL of 10% DMSO (O'Donnell et al, 1981).
    D) TOXIC ENCEPHALOPATHY
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - An 82-year-old man who received an unknown dose of DMSO IV 5 days/week for 3 weeks developed confusion, lethargy, and disorientation during the third week. Later he was noted to have agitation, dysarthria, and hypoactive reflexes. These symptoms persisted for 8 days after discontinuation of the therapy, and emotional lability remained for another week (Bond et al, 1989).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, diarrhea, anorexia and constipation may occur.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting have been seen (O'Donnell et al, 1981).
    B) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Both diarrhea and constipation have been reported (Brobyn, 1975).
    C) LOSS OF APPETITE
    1) WITH THERAPEUTIC USE
    a) Anorexia may be seen (Brobyn, 1975).

Hepatic

    3.9.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Elevated liver enzymes have been reported, and two questionable cases of liver toxicity have been reported.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Two cases of liver toxicity have been reported, but there is considerable doubt whether DMSO was the causative agent (Yellowlees et al, 1980). Others have reported elevated liver enzymes without serious toxicity (Knott, 1980).

Genitourinary

    3.10.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) A dose dependent hematuria is possible.
    3.10.2) CLINICAL EFFECTS
    A) BLOOD IN URINE
    1) WITH THERAPEUTIC USE
    a) Dose dependent hematuria and burning on urination have reported (Muther & Bennett, 1980).
    B) POLYURIA
    1) WITH THERAPEUTIC USE
    a) DMSO promotes diuresis (de la Torre et al, 1975).

Hematologic

    3.13.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Possible eosinophilia has been reported, and when given IV, hemolysis and increased serum osmolality has been reported.
    3.13.2) CLINICAL EFFECTS
    A) HEMOLYSIS
    1) WITH THERAPEUTIC USE
    a) Intravenous administration of a 13% to 15% DMSO solution in D5W may cause hemolysis and increase serum osmolality (Runckel & Swanson, 1980).
    b) The amount of hemolysis seen will vary with DMSO concentration, rate of administration, and solution osmolality (Gerhards & Gibian, 1967; Distefano & Klahn, 1965; Caujolle et al, 1967).
    B) EOSINOPHIL COUNT RAISED
    1) WITH THERAPEUTIC USE
    a) Eosinophilia has also been reported (Brobyn, 1975).

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Stinging and burning of the skin as well as rashes and vesicles have been seen. A heat reaction may occur if administered on wet skin. Systemic contact dermatitis has occurred from intravesical administration.
    3.14.2) CLINICAL EFFECTS
    A) PAIN
    1) WITH THERAPEUTIC USE
    a) Concentrations of greater than 10% cause a stinging and burning sensation. Most therapeutic applications use a 60 to 90% gel or solution. If the skin is not clean and dry, water will catalytically react to produce heat. Administration of a greater than 50% solution may cause erythematous reactions (Olson, 1982).
    b) CASE REPORT - A 19-year-old male experienced burning and swelling of the skin following application of topical DMSO 99% (v/v) for a suspected daunorubicin extravasation. Symptoms persisted for 2 hours despite cooling measures. The patient was re-challenged 5 days later and incurred pain, burning, inflammation and erythema of the treated area. All symptoms resolved within 4 hours (Creus et al, 2002).
    B) URTICARIA
    1) WITH THERAPEUTIC USE
    a) Urticarial rash and vesicles have been reported possibly due to the release of histamine (Luery et al, 1984). DMSO is a counterirritant.
    C) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - Dermatitis occurred in a 49-year-old man after intravesical instillation of 50% aqueous solution of dimethyl sulfoxide for the treatment of interstitial cystitis. The reaction recurred 2 days following an additional treatment and when patch tests were performed with diluted DMSO preparations (Nishimura et al, 1988).

Immunologic

    3.19.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) DMSO releases histamine from mast cells.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) DMSO releases histamine from mast cells, causing rash and hypersensitivity reactions (Luery et al, 1984).
    B) DISORDER OF IMMUNE FUNCTION
    1) WITH THERAPEUTIC USE
    a) DMSO is also suspected to cause antiinflammatory activity and immunosuppressive activity (Weetman et al, 1982).

Reproductive

    3.20.1) SUMMARY
    A) Data for humans are lacking. Teratogenic effects have been seen in animals. permatozoa of honey bees frozen with DMSO as the cryoprotectant produced total sterility in 3% of the female progeny. Total sterility is very rare in honey bees.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) ANIMALS - Teratogenic effects have been seen in animals (Prod Info Rimso-50(R), dimethyl sulfoxide, 1990).
    B) CONGENITAL ANOMALY
    1) HUMAN - Data for humans are still lacking (Product Info Rimso-50(R), 1990).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) HONEY BEES - Harbo (1986) found that spermatozoa of honey bees frozen with DMSO as the cryoprotectant produced total sterility in 3% of the female progeny. Total sterility is very rare in honey bees (Hitchcock, 1956).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS67-68-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) RTECS (1991) states DMSO is an equivocal tumorigenic agent by their criteria.

Genotoxicity

    A) DMSO tested positive for mutagenicity in bacteria and caused DNA damage in a mouse model (RTECS , 1991).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Although analysis is available from special laboratories, the levels have little clinical meaning.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor hepatic and renal function.

Methods

    A) OTHER
    1) DMSO and its metabolites could be analyzed in special laboratories, but since there is no therapeutic or toxic blood level, this would have little meaning.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Although analysis is available from special laboratories, the levels have little clinical meaning.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Emesis should NOT be induced, since this is a solvent and aspiration is possible.
    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) SUMMARY
    1) Emesis should not be induced, since this is a solvent and aspiration is possible. If large amounts have been ingested, consider lavage after intubation.
    B) ACTIVATED CHARCOAL
    1) 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.
    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).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Evaluate liver function, kidney function, hemoglobin, and platelet count

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).
    6.8.2) TREATMENT
    A) GENERAL TREATMENT
    1) Systemic effects should be treated as above.
    B) IRRITATION SYMPTOM
    1) Although lens toxicity has not been seen in humans, consider an ophthalmic examination at the time of the exposure and in one week for any changes.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DMSO is rapidly absorbed (usually less than 30 minutes) so rapid washing is important.
    2) 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) PROCEDURE EDUCATION
    1) DMSO carries other chemicals through the skin. A careful history should be taken as to what drugs/chemicals might have been on the skin prior to exposure (Olson, 1982).
    B) IRRITATION SYMPTOM
    1) Chemical irritation resulting in a rash is common and should be treated symptomatically. If severe or persistent, the rash should be evaluated by a physician.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) There are no data evaluating hemoperfusion or hemodialysis.
    B) PERITONEAL DIALYSIS
    1) In one case with serious liver toxicity (Yellowlees et al, 1980) peritoneal dialysis was tried, with little apparent clinical effect.

Abstracts

Case Reports

    A) ADULT
    1) An 82-year-old man received an unknown dose of DMSO IV 5 days/week for 3 weeks. During the third week he developed confusion, lethargy, and disorientation. After the final infusion, he was admitted with agitation, dysarthria, and hypoactive reflexes. Laboratory abnormalities were suggestive of dehydration and improved with hydration (serum osmolality 311 mmol/L and serum sodium 152 mmol/L). Encephalopathic signs persisted for 7 days and emotional lability for another week. A DMSO serum concentration 4 days after discontinuation was 160 mg/dL, which is comparable to peak levels achieved 4 hours after administration of 1 g/kg (Bond et al, 1989).

Range Of Toxicity

Summary

    A) There are no therapeutic or toxic blood levels established.

Therapeutic Dose

    7.2.1) ADULT
    A) INTERSTITIAL CYSTITIS
    1) DMSO is only approved for use in the treatment of interstitial cystitis, where 50 mL of a 50% solution is instilled directly into the bladder by catheter or aseptic syringe and allowed to remain for 15 minutes. Treatment should be repeated every 2 weeks to obtain maximum symptomatic relief (Prod Info RIMSO-50(R) intravesical irrigant, 2012).
    2) For patients with severe interstitial cystitis with very sensitive bladders, the initial treatment, should be done under anesthesia (eg, saddle block) (Prod Info RIMSO-50(R) intravesical irrigant, 2012).

Minimum Lethal Exposure

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

Maximum Tolerated Exposure

    A) ACUTE
    1) The lowest published toxic dose for man (intravenous route) was 606 mg/kg. Toxic effects were to the gastrointestinal system (nausea or vomiting) and the liver (jaundice, other not specified) (RTECS , 2001).
    2) The lowest published toxic dose for woman (dermal route) was 1800 mg/kg. Toxic effects were to the respiratory system (dyspnea, cyanosis) and hematologic (changes not specified) (RTECS , 2001).
    B) ANIMAL DATA
    1) Dimethyl sulfoxide applied intragastrically for 10 minutes in rats caused extensive mucosal damage. In concentrations of 5%, 10%, or 100%, dimethyl sulfoxide caused superficial damage to 33%, 36%, and 97%, respectively, of the corpus mucosa, and 28%, 44%, and 96%, respectively, of the antral mucosa. Concentrated dimethyl sulfoxide also caused damage to the pits and glands in some areas of the mucosa (Sorbye et al, 1993).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) There is no therapeutic or toxic blood level established.
    b) The serum DMSO level in an elderly patient with encephalopathy was 160 milligrams/deciliter four days after discontinuation of therapy. The corresponding metabolite level (DMSO2) was 300 milligrams/deciliter (Bond et al, 1989).

Workplace Standards

    A) ACGIH TLV Values for CAS67-68-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS67-68-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS67-68-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS67-68-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 2500 mg/kg (RTECS, 2001)
    B) LD50- (ORAL)MOUSE:
    1) 7920 mg/kg (RTECS, 2001)
    C) LD50- (SKIN)MOUSE:
    1) 50 gm/kg (RTECS, 2001)
    D) LD50- (SUBCUTANEOUS)MOUSE:
    1) 14 gm/kg (RTECS, 2001)
    E) LD50- (INTRAPERITONEAL)RAT:
    1) 8200 mg/kg (RTECS, 2001)
    F) LD50- (ORAL)RAT:
    1) 14500 mg/kg (RTECS, 2001)
    G) LD50- (SKIN)RAT:
    1) 40 gm/kg (RTECS, 2001)
    H) LD50- (SUBCUTANEOUS)RAT:
    1) 12 gm/kg (RTECS, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) DMSO has several possible actions.
    1) LOCAL ANESTHETIC (Percy & Carson, 1981) - DMSO lowers the conduction velocity of isolated nerves in ANIMALS, and provided pain relief equal to morphine when given topically, SQ, IP, and IV, but not orally (Jimenez & Wilkens, 1982).
    2) ANTIINFLAMMATORY ACTIONS may be due to its ability to scavenge free radicals, stabilize lysosomal membranes (Jimenez & Wilkens, 1982), and produce vasodilation.
    3) COLLAGEN - DMSO has an effect on collagen fibers. The mechanism is unknown but may have to do with dissolving collagen and leaving elastic fibers intact.
    4) FREEZING - There is considerable debate whether DMSO protects cells from freezing and will reduce increased intracranial pressure. These effects are still under investigation.
    5) CARRIER - DMSO enhances the percutaneous absorption of substances or molecular weight less than 3,000. It also decreases movement of water soluble substances once in the skin, thus creating a dermal reservoir.
    6) DMSO is a free radical hydroxide trapper (Brayton, 1986).
    7) In ANIMALS, DMSO temporarily reduced autoantibody levels. Its use may have a temporary immunosuppressive effect.

Toxicologic Mechanism

    A) DMSO enhanced cholinergic contractions in isolated guinea pig central airways induced by transmural electrical field stimulation (Schreiber & Slapke, 1990). The authors speculate that enhancement of neurotransmission might be a possible cause of DMSO-induced neurotoxicity.
    B) DMSO may induce histamine release from mast cells (Brayton, 1986).

Physicochemical

Physical Characteristics

    A) Dimethyl sulfoxide is a clear (water-white), very hygroscopic liquid, with slightly sulfurous odor (or practically no odor) (Budavari, 1996).
    B) Slightly bitter taste with a sweet after-taste (Budavari, 1996).
    C) Dimethyl sulfide is excreted through the lungs and skin, and is responsible for the characteristic odor (garlic-like) from patients (S Sweetman , 2001).

Molecular Weight

    A) 78.14 (Budavari, 1996)

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