DMSO Health & Safety

Acute Toxicity

Evaluation of the degree of hazard due to contact with a chemical is usually by its single-dose LD-50. The LD-50 is the Lethal Dose in number of grams of DMSO per kilogram of body weight which results in 50% mortality of the test animals under standardized conditions. Dozens of test data reports are available from many laboratories throughout the world. The reported LD-50 may vary but the data confirm a low level of toxicity. One published summary is the following:

Single-Dose Toxicity of DMSO as LD₅₀ (1) (g/kg)

Using the monkey as an example, it would take more than 1.6 pounds applied to the skin or 0.6 pounds taken by mouth or injected directly into the blood stream, to have a 50% mortality rate in a group weighing 150 pounds each.

Other studies have shown that DMSO has low acute toxicity and is practically non-toxic (LD₅₀>5 g/kg) by ingestion or dermal application. Rat oral LD₅₀ are reported from 17.4 to 28.3 g/kg, whereas LD₅₀ for mice have been reported from 16.5 to 24.6 g/kg. The acute dermal LD⁵⁰ is 40 g/kg for the rat and 50 g/kg for the mouse, while dermal LD50 > 11 g/kg are reported for both dogs (beagles) and primates (rhesus monkeys). Although DMSO can cause skin and eye irritation, it is not a skin sensitizer.

In addition to LD₅₀ explained above, another unit LD₅₀ is used to evaluate the hazard from inhalation. LD50 is the Lethal Concentration that kills 50% of the test animals. The acute rat inhalation LD₅₀ is greater than 1.6 mg /l, the only dose level tested, and which is also a No-Observed-Effect-Level (NOEL).¹⁰

Subchronic Toxicity

The subchronic rat inhalation NOEL of 200 mg/m³(0.2 mg/I) was determined from a single concentration study. Extensive monitoring of human patients have shown that DMSO does not affect human renal function. DMSO is a diuretic but no sign of kidney damage has been found in humans or laboratory animals after repeated DMSO treatment. Hemolysis has been reported in animals that received DMSO intravenously.

Skin Exposure

DMSO easily penetrates the skin (176 ± 42 g/m2/hr) compared to, for example, water (14.8 ± 0.1 g/m2/hr), but because of DMSO’s low toxicity (see previous section) and the fact that this same permeability test showed DMSO does not carry less-permeable substances with it through the skin, it can be concluded that DMSO does not pose a significant threat by skin absorption. The penetration rate of DMSO in solutions is a direct function of the mole fraction of DMSO. (Ursin, et. al. 1995)¹⁴. Although DMSO readily penetrates human skin in concentrations of 70-100%, at concentrations of 67% or less, DMSO molecules are hydrated, which greatly reduces dermal penetration (Sulzberger et. al., 1966; Brayton, 1986: Woodford and Barry, 1986).

No significant abnormalities were found in extensive physical examinations or analyses of blood and urine during repeated applications of large amounts of DMSO to the skin of humans over a long period of time. This was reported by Dr. Richard Brobyn2 to the New York Academy of Sciences. DMSO was used in two human studies lasting 14 and 90 days. In each case, one gram of DMSO per kilogram of body weight was applied each day by each subject to his own skin. In an (80 kg = 176 lb) individual, it was 80 grams or 2.7 fl. oz. This amount required up to 2 hours for complete absorption from the 90% DMSO gel.

No conclusive evidence of intolerance resulted from dermal application of 9 grams/kilogram of 90% DMSO to Rhesus monkeys daily for 18 months. In a small (50 kg = 110 lb.) individual, this would amount to daily applications of 15.2 fluid ounces or nearly a pint of 90% DMSO.

Observation has indicated that skin application, particularly if frequent with large amounts of DMSO, may result in reddening, itching and burning at the application site. Exposure to large amounts of DMSO by skin or elsewhere may result in sedation, headache, nausea or dizziness.

Chronic Toxicity

DMSO is not listed as a carcinogen by regulatory agencies such as IARC, NTP, OSHA or ACGIH, based on reviews of numerous studies. An 18-month study with rhesus monkeys established an oral NOEL of 3300 mg/kg/day. No tumors were observed and bone marrow smears from the monkeys that received oral or topical doses of DMSO at up to 9g/kg/day.¹² This is comparable to an average human (70 kg or 154 lbs) consuming approximately 210 g (or nearly 1/2 pound) DMSO per day, i.e., 3g/kg/day. In fact, 84 humans that have received daily topical treatment of 2.8 g DMSO/kg/day (equivalent to nearly 1/2 pound/day/person) for up to three months showed no DMSO-related effects beyond occasional skin irritation, garlic breath and body odor. Additionally, (Hull et al. 1969)⁷ found no DMSO-related effects in any of the 38 humans, age 21-55, who received a topical application of an 80% DMSO gel in a single daily dose of 1 g/kg for 12 weeks.

Continuing research has demonstrated that the ocular effects reported from DMSO treatment of dogs, rabbits, guinea pigs and swine are species-specific and not reproducible in primates, including humans. Even though ocular toxicity, specifically lenticular refractive changes, have been reported in some animal studies with dogs, rabbits and swine (Rubin and Barnett, 1967; Smith et al. 1969)³and in guinea pigs (Rengstarff et al.,1972)⁴, it was subsequently demonstrated that the ocular effect was species-specific and was not

reproducible in primates, including humans (Smith et al., 1969)³ (de la Torre et al. 1981)⁵. Furthermore, full ophthalmologic examinations revealed no DMSO-related lenticular changes in any of 84 patients treated three times daily for three months with topical 70% DMSO, topical 2% DMSO or 0.85% normal saline (maximum theoretical dosage of 2.6 g DMSO/kg/day), which is comparable to dosages used in the animal studies (Shirley et al.,1988)⁶.

DMSO is metabolized in humans by oxidation to dimethyl sulfone, DMSO₂ or by reduction to dimethyl sulfide, DMS. DMSO and DMSO₂ are excreted in the urine and feces. DMS is eliminated through the breath and skin with a characteristic “garlic” or “oyster-like” odor. Human excretion of orally administered DMSO is complete within 120 hours, with urinary excretion being the primary pathway. The rate of renal clearance has been shown to be similar for chronic and singly administered doses regardless of dose concentration. No residual accumulation of DMSO has been reported in humans or lower animals who have received DMSO treatment for protracted periods of time, regardless of route of dose administration.

Metabolite Toxicity

The metabolites of DMSO are DMSO2, which naturally occurs at low levels in human urine (PDR, 1994)⁸, and DMS, which naturally occurs in plants, the atmosphere, and lakes and oceans (Pearson et al., 1981)⁹. Both of these metabolites are readily excreted from the body. Based on their widespread natural occurrence and ready degradation and/or excretion, the production of these metabolites from the proposed use of DMSO on food producing plants is not expected to pose any toxicological concern.

Inhalation

Fishman and coworkers at the Naval Medical Center (10) performed many toxicological measurements on the exposure of rats to DMSO vapors. The following single and repeated exposures were made:

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Extensive blood and tissue samples were examined. No evidence of toxicity was demonstrated. No significant changes were noted during or following repeated exposure. We suggest, as a good hygiene practice, avoiding exposure to DMSO sprays or mists and very high doses of DMSO vapors.

Effects on Other Organisms

1. Effects on Plants. DMSO by itself and DMSO with antibiotics, minerals, nutrients, pesticides and other materials have been sprayed on, injected into, painted on, and fed to a variety of plants. It has a low order of phytotoxicity in these applications.
2. Effects on Fish.Wilford¹¹investigated the toxicity of DMSO in water to 9 species of fish. At 96 hours, the LC-50 was 32,000 to 43,000 ppm DMSO (3•4%). This is far less toxic than acetone (fingernail polish remover) and other widely used solvents.
3. Effects on Sewage Plants. DMSO is biodegradable in biological systems. It is converted in part to methyl sulfone and to dimethyl sulfide. The sulfone is stable and inert and degraded only slowly by microorganisms or physical factors. At high concentrations, some DMS may escape, producing its characteristic odor.

Natural Occurrences in Food

The occurrence of DMSO and its metabolites, dimethyl sulfide and methyl sulfone (DMSO₂), have been widely reported in a variety of foods. Pearson⁹ and coworkers reported finding 0.07 to 16 ppm DMSO, along with DMSO₂, in 14 fruits, vegetables or beverages. This natural occurrence insures that the body can dispose of DMSO by well-established metabolic processes. Naturally-occurring DMSO has been identified in alfalfa, asparagus, barley, beans, beets, cabbage, corn, cucumbers, oats, onions, Swiss chard, tomatoes, apples, raspberries, spearmint, beer, milk, coffee and tea. DMSO concentrations in fresh fruits, vegetables and grains ranged from undetectable (<0.05 parts per million) to 1.8 ppm.

Genotoxicity

DMSO is not mutagenic to Salmonella, Drosophila, and fish cell cultures. Because DMSO is so non-reactive as a mutagen, it is widely used as a solvent in mutagenicity testing. Although DMSO is bacteriostatic or bactericidal at concentrations of 5-50%, there is no evidence that DMSO causes chromosomal aberrations at levels that are not directly toxic to cells. Bone marrow smears from primates (rhesus monkeys) that received oral or topical doses of DMSO for 18 months showed no DMSO effects (Vogin et al., 1970)¹². An in vivo cytogenetics study of DMSO administered by intraperitoneal injection to male rats found a significant increase in aberrant femoral bone marrow cells when compared to controls (Kapp and Eventoff, 1980)¹³. However, evidence from the Salmonella studies and other toxicology data, especially the teratology data, suggests that the increase in aberrant femoral cells likely resulted from direct toxicity of DMSO injected into an animal instead of a classic “mutagenic” response.

According to Brayton (1986), there are no documented adverse genetic effects reported as a result of medicinal DMSO uses (including quasi-medicinal uses for treatment of arthritis or sprains and strains). Additionally, no adverse genetic effects have been reported from occupational exposure to DMSO in over 40 years of industrial use (Brayton, 1986). There is no evidence that DMSO causes chromosomal aberrations at levels that are not directly toxic to cells.

Reproductive and Developmental Toxicity

A mouse teratology NOEL of 12g/kg/day has been established based on research with a 50% DMSO solution administered orally. Additional teratogenicity studies of orally administered DMSO to pregnant mice, rats, rabbits and guinea pigs have demonstrated that DMSO is not a teratogen in mammals except at high levels that cause overt maternal toxicity and are coincident with the maximum tolerated dose. The data suggest that DMSO is not teratogenic at low levels regardless of the route of administration. Finally, the teratogenic potential of DMSO is dependent on the route of administration, the dose level and gestation stage at exposure.

The one study (Robens, 1968) that did show evidence of teratogenic effects (in hamsters, one of three animal species tested) from oral administration of DMSO is inappropriate to use for a teratologic evaluation of DMSO for the following reasons:

• DMSO was not the compound of interest but was used only as a solvent control at two very high dose levels which precluded establishing a NOEL.
• One of the DMSO levels tested resulted in maternal death and was clearly beyond the maximum tolerated dose (MTD).

DMSO is not considered to be directly embryotoxic and has been shown to be a successful cryoprotectant for mammalian semen and embryos (Brayton, 1986).

In summary, the evidence of the above teratology data suggests that:

1. DMSO is not a teratogen to mammals when administered via oral and dermal routes at dose levels that do not produce overt maternal toxicity.
2. DMSO is not a teratogen at low dose levels regardless of the route of administration.
3. The teratogenic potential of DMSO is dependent on route of administration, the dose level and the gestational time of exposure.

DMSO Solutions From Gaylord Chemical

The high polarity and low toxicity of DMSO makes it an ideal solvent for numerous industrical applications including pharmaceutical syntheses. Gaylord Chemical’s Procipient® is the only grade of DMSO suitable for healthcare and drug delivery applications. As the preeminent manufacturer of DMS and DMSO we pride ourselves on the quality of our products and world-class customer service. If you would like more information about our products, we would love to hear from you.

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