Dmso toxicity

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What Is DMSO?

Gloria Ramirez January 11, — February 19, [1] was an American woman from Riverside, California who was dubbed "the Toxic Lady" or "the Toxic Woman" by the media when several hospital workers became ill after exposure to her body and blood. She had been admitted to the emergency department while suffering from late-stage cervical cancer. While treating Ramirez, several hospital workers fainted and others experienced symptoms such as shortness of breath and muscle spasms. Five workers required hospitalization, one of whom remained in an intensive care unit for two weeks. Shortly after arriving at the hospital, Ramirez died from complications related to cancer. The incident was initially considered to be a case of mass hysteria. An investigation by Lawrence Livermore National Laboratory proposed that Ramirez had been self-administering dimethyl sulfoxide as a treatment for pain, which converted into dimethyl sulfatean extremely poisonous and highly carcinogenic alkylating agent, via a series of chemical reactions in the emergency department. Although this theory has been endorsed by the Riverside Coroner's Office and published in the journal Forensic Science Internationalit is still a matter of debate in the scientific community. She was extremely confused and was suffering from tachycardia and Cheyne—Stokes respiration. The medical staff injected her with diazepammidazolamand lorazepam to sedate her. When it became clear that Ramirez was responding poorly to treatment, the staff tried to defibrillate her heart; at that point several people saw an oily sheen covering Ramirez's body, and some noticed a fruity, garlic-like odor that they thought was coming from her mouth. A registered nurse named Susan Kane attempted to draw blood from Ramirez's arm and noticed an ammonia -like smell coming from the tube. She passed the syringe to Julie Gorchynski, a medical resident, who noticed manila-colored particles floating in the blood. At this point, Kane fainted and was removed from the room. Shortly thereafter, Gorchynski began to feel nauseated. Complaining that she was lightheaded, she left the trauma room and sat at a nurse's desk. A staff member asked her if she was okay, but before she could respond she also fainted. Maureen Welch, a respiratory therapist who was assisting in the trauma room was the third to pass out. The staff was then ordered to evacuate all emergency department patients to the parking lot outside the hospital. Overall, 23 people became ill and five were hospitalized. The county health department called in California's Department of Health and Human Serviceswhich put two scientists, Drs.

Dimethyl sulfoxide (DMSO): a review.


Dimethyl sulfoxide DMSO is widely used in biological studies as a cryoprotective agent for cells and tissues, and also for cryopreserved platelets PLT s. Apoptosis of EA hy cells with 0. On the basis of these findings, it was concluded that DMSO was toxic to the hematologic system. This should be taken into account when assessing the infusion effects of cryopreserved PLT s or other blood products requiring DMSO as a vehicle, such as cryopreserved stem cells, in order to avoid adverse therapeutic effects. Dimethyl sulfoxide [DMSO, CH 3 2 SO], a highly polar organic liquid that has one polar sulfinyl domain and two apolar methyl groups, is used widely as a chemical solvent 12. Because of its ability to penetrate biological membranes, it is used as an agent for hypothermal storage of blood cells, including the cryopreservation of platelets PLTs 34. DMSO can readily penetrate into living cells and modulates membrane permeability, which gives it cryoprotective property 5. DMSO decreases the formation of intracellular ice crystals; therefore, frozen injuries of cells and tissues mixed with DMSO can be reduced 6. In general, DMSO has low acute and chronic toxicity for animal, plant, and aquatic life 89. According to the reports, in vivo studies investigating the metabolic fate of DMSO in human indicate that DMSO is rapidly absorbed, reaching a peak in serum at 4—8 h after oral or transcutaneous administrations, is cleared from the blood within h after ingestion of a single dose, and is primarily excreted in urine unchanged or as DMSO 2 the major metabolite found in human 101112 Although clinic studies have reported that PLT products cryopreserved with DMSO were infused into the human body, the effects have been controversial. Massive intravenous infusion with DMSO cryopreserved products can cause occasional skin irritation, garlicky breath and body odor, and liver and kidney dysfunction. There have been reports of leukemia patients presenting with abdominal pain, nausea, headache, bradycardia, and other symptoms, even death 15161718192021 These investigations were mostly restricted to the skin, oral cavity, and respiratory tract, less is known about effects on the hematologic system. Thus, it was important for us to evaluate adverse effects of DMSO itself on the hematologic system. For that purpose, we investigated the effects of DMSO on the membrane stability and function of blood cells and the proliferation of vascular endothelial cells involved in the infusion response, using in vitro blood cells and EAhy cells stimulated with DMSO or without DMSO control. The study was approved by the Ethics Committee of the Academy of Military Medical Sciences and all aspects of the study comply with the Declaration of Helsinki. Ethics Committee of the Academy of Military Medical Sciences specifically approved that no informed consent was required because data were going to be analyzed anonymously. RBCs had no other treatment. Finally, we selected 0. Free hemoglobin levels were examined using the detection kit. FHb was measured by ultraviolet spectrophotometer Persee, China. After incubation for 6—9 min, PLT aggregation activity was measured, and the maximum aggregation rate was used to represent platelet aggregation activation. The corresponding platelet poor plasma PPP was used as the control in light transmission method. At specific times every 0. Platelet apoptosis experiments were done using the same procedure described for RBCs. These cells were individually incubated with or without DMSO 0. Cell appearance was observed daily by optical microscope. Cell proliferation was assayed by MTS assay for five consecutive days according to the manufacturer's protocol.

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At Burst Biologics, we see a lot of double-edged swords throughout science and medicine. Medicine can treat all kinds of conditions but has potential side effects. Surgery carries the risk of complications, even if it means a new lease on life. Dimethyl sulfoxide is a colorless liquid discovered in 19th century Germany as a byproduct of wood pulp when producing paper. One of its most notable properties is its ability to permeate across cell membranes. This quickly proved useful for dermatological conditions like skin inflammation, or scleroderma. The year marked the first trial of DMSO usage to prevent freezing damage to living cells. However, all these decades later, the chemical is still only approved by the FDA for a single function. On the positive side, DMSO can permeate across cell membranes, allowing it to inhibit intracellular ice formation. But even with all these great properties, DMSO has its drawbacks. The chemical is associated with possible toxicity and a range of serious side effects. Also, prolonged exposure to dimethyl sulfoxide directly impacts cellular function and growth. The same effect can occur in a clinical setting. Once cells begin to thaw, they are susceptible to the cytotoxic effects of dimethyl sulfoxide. With that in mind, how exactly does this chemical affect patients in the real world? As serious as these conditions are, this is only a partial list of the identified ARs related to DMSO, based on many studies centered around the physiological role of the chemical in ARsfrom neurotoxic reactions to shock. Studies also show that the adverse effects are cumulative. Patients receiving multi-dose therapies containing DMSO may suffer progressively more severe symptoms over time. In any allograft or stem cell transplantation procedure, there are many components involved. Some of these factors, such as dead cell debris after thaw or the low temperature of infused products, can also lead to ARs. If we know that DMSO has the potential to be harmful to patients, the next question is, what do we do with that information? After all, cryopreservation is still a necessity if we want patients to enjoy the benefits of allografts and tissue supplementation. Here are four other widely discussed strategies for minimizing adverse reactions to dimethyl sulfoxide in cryopreserved grafts:. The first three solutions hold some promise, but the bottom line is, nothing is safer than simply avoiding DMSO altogether. We developed a patent-pending process to preserve product integrity and address the potentially harmful agent of DMSO in our cryopreservation media. Our internal team has demonstrated the efficacy of this DMSO-free cryopreservation medium, which enlists USP grade non-toxic ingredients. Ultimately, the products do their job well without even a hint of dimethyl sulfoxide. Learn more about our committment to being DMSO-free. Previous Next. Common allergic reactions include flushing, rash, and edema. Gastrointestinal — Affecting the limbic-hypothalamic pathways, DMSO can result in symptoms like nausea, abdominal pain, and emesis. Renal — The incidence of kidney-related ARs is comparatively low but includes symptoms like hemoglobinuria, proteinuria, and urine incontinence. Cardiovascular — Symptoms include hypertension, arrhythmias, tachycardia, shock, cardiac arrest, and seizure. Neurological — Symptoms include bilateral thalamic infarction, blurred vision, severe encephalopathy, cognition, muscle weakness, and numbness. Hepatic — Symptoms include progressive jaundice. Here are four other widely discussed strategies for minimizing adverse reactions to dimethyl sulfoxide in cryopreserved grafts: Reducing overall DMSO concentration Administering medication before and after transplantation Optimizing the infusion procedure Using alternative CPAs for cryopreservation The first three solutions hold some promise, but the bottom line is, nothing is safer than simply avoiding DMSO altogether. Share This Story! Facebook Twitter LinkedIn Email. Related Posts.

How Safe is Dimethyl Sulfoxide (DMSO): Why We Ditched DMSO


DMSO is an unusually nontoxic organic solvent that is finding increased use in pharmaceutical synthesis, the manufacture of electronics, and drug delivery in the body. Its use is supported by over 50 years of industrial and academic experience. Reproductive and Developmental Toxicity. A great number of toxicological, environmental and medical studies have been performed with DMSO to determine the safety of this chemical. Many of these studies have been published as references at the end of this bulletin. This summary only lists some of the results found, but in-depth details are reported in the original publications. DMSO is a commercially manufactured dipolar aprotic solvent which is also a naturally occurring substance. DMSO is created in the atmosphere at a rate of billion pounds per year from dimethyl sulfide, which is produced by metabolic processes in soil and sediments. DMSO is also found in natural waters and soil. Metabolism of DMSO in soil by microorganisms results in the formation of sulfur and dimethyl sulfide. DMSO has low acute and chronic toxicity for animal, plant and aquatic life. Exposure to test organisms at high concentrations by contact, ingestion or inhalation consistently show low toxicity. DMSO is not listed as a carcinogen by regulatory authorities and is actually used as a neutral solvent in the Ames mutagenicity tests. DMSO is not a teratogen in mice, rats or rabbits. Because of this low potential for toxicity, the EPA has approved DMSO as a solvent or a cosolvent, in pesticides which are applied before crop emergence or prior to the formation of edible parts of food plants. Since then, a large number of people have received this treatment. DMSO has been approved for use in other pharmaceutical formulations in the U. In addition, inthe FDA endorsed the recommendation of the expert working group of the International Conference on Harmonization relative to the residual solvents in pharmaceuticals. DMSO was placed in the safest category, class 3 solvents, with low toxic potential. Class 3 includes no solvent known as a human health hazard at levels normally accepted in pharmaceuticals. Solvents in Class 3 Table 1 may be regarded as less toxic and of lower risk to human health. Available data indicate that they are less toxic in acute or short-term studies and negative in genotoxicity studies. It is considered that amounts of these residual solvents of 50 mg per day or less corresponding to 5, ppm or 0. Higher amounts may also be acceptable provided they are realistic in relation to manufacturing capability and good manufacturing practice GMP. When handling or using DMSO, a potential for exposure exists. Therefore, the following information should be considered regarding possible exposure routes. Skin contact, the most likely exposure, has been extensively studied with humans and animals. Large dosages over prolonged periods showed only minor toxic effects such as minor skin irritation, itching and burning Although DMSO is absorbed rapidly through the skin, it has a low degree of toxicity via dermal route of administration. Also, it has been found that the molecular weight of chemical compounds can preclude their transdermal penetration by DMSO. DMSO is not alone in its ability to penetrate human skin, and proper industrial hygiene should be practiced when working with all solvents. Table 2 provides relative permeability data for some common solvents. Some of the physical properties of DMSO are included in the following table.

Unexpected low-dose toxicity of the universal solvent DMSO.

Dimethyl sulfoxide DMSOan oxidation product of dimethyl sulfide, is an exceptional solvent possessing a number of commercial uses. Its structural formula is:. It freely mixes with water with the evolution of heat and lowers the freezing point of aqueous solutions. It is soluble in many other compounds including ethanol, acetone, diethyl ether, glycerin, toluene, benzene and chloroform. DMSO is a solvent for many aromatic and unsaturated hydrocarbons as well as inorganic salts and nitrogen-containing compounds. DMSO has a high dielectric constant due to the polarity of the sulfur-oxygen bond. Its basicity is slightly greater than water due to enhanced electron density at the oxygen atom. It forms crystalline salts with strong protic acids and coordinates with Lewis acids. It modifies hydrogen bonding. DMSO is a hygroscopic stable organic liquid essentially odorless and water white in color. Other physical characteristics include:. Dimethyl sulfoxide when administered topically or orally is rapidly absorbed and distributed in living material. Using S 35 -labeled DMSO 1 the maximal blood concentration after cutaneous application was achieved in approximately 10 minutes in rats and less than 1 hour in dogs. In rats and dogs the substance did not accumulate in the organs but the concentration in the treated skin and underlying muscle was increased. The main route of excretion is via the urine partially dependent on the species and route of application. In rats there was no significant difference in the elimination half-time of 6 to 8 hours after intravenous or cutaneous administration; in the dog, the elimination half-time was 1. In another S 35 -labeled study 2 with DMSO, following intravenous or cutaneous administration, the only metabolite detectable in the urine of humans and rats, was dimethyl sulfone DMSO 2. Plasma radioactivity after an intraperitoneal dose was highest at 0. When applied dermally, levels remained constant for 6 hours. A peculiar sweetish odor was noted in the exhaled breath of cats treated with dimethyl sulfoxide 4. The compound responsible for this was identified as dimethyl sulfide. The same odor has been noted in all species treated with the compound. The original biological applications of DMSO were primarily confined to its use in preserving various tissues and cellular elements including blood 7blood cells and bone marrow 8leukocytes 9lymphocytes 10platelets 11spermatozoa 12, 13, 14corneal grafts 15, 16skin 17tissue culture cells 18, 19, 20, 21 and trypanosomes 22by freezing techniques. DMSO has also been investigated as a radioprotective agent 23, In early studies with plants it was claimed that DMSO exerted a profound effect on the biologic membrane, altering their natural selectivity and enhancing the penetration of antibiotics and fungicides Utilizing a similar technique the transport of physiologically active insulin across the intact bladder mucosa was demonstrated. Results were judged on a decrease in blood sugar levels over that of controls In vivo and in vitro methods demonstrated that DMSO enhanced human percutaneous absorption of various compounds including steroids, vasoconstrictors, antiperspirants and dyes, as well as an anthelmintic thiabendazole and a skin antiseptic hexachlorophene 27, 28, 29, 60, 61, Enhancement was not due to irreversible damage to the stratum corneum DMSO has been stated to increase the penetration of low molecular weight allergens such as penicillin G but not large molecular weight allergens such as house dust The rate of passage of tritiated water in the presence of DMSO on the epidermis of the hairless mouse was measured in vitro. It was concluded that the concentration of DMSO used seemed more significant than the time of exposure in establishing the effect on the water barrier Other solvents, including water, also appeared to permit some drug penetration in this study

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