The toxicology of dimethyl sulfoxide (DMSO), which is a water-miscible, clear liquid at ordinary room temperatures, has been studied in animals in a number of laboratories since the two initial reports on this subject appeared in 1963.\"' I n fact, a t the present time we are aware of 14 such studies involving eight species, ten routes of administration and many different dosage schedules. These studies are summarized in this report in two different manners. First, they have been arbitrarily grouped for presentation into single-dose studies involving the administration of only one dose of DMSO to each animal and repeated-dose studies involving repeated dosing of the same animal. Each of these, in turn, has been organized according to the route of administration and to the particular species studied. Then, because no species-related differences in response to DMSO have been observed, the biological actions of DMSO which have been seen in these studies have been enumerated without regard to the particular species in which the action was observed. Finally, some comments are made concerning the relation of these studies in animals to the clinical use of DMSO.

The single--and repeated--dose toxicity of dimethyl sulfoxide.

THE high incidence of oral cancer in the Far East is generally attributed to the habitual use of betel nut “quids” which may contain, as well as betel nut, cured tobacco and various other organic and inorganic materials1–4. Attempts to extract from betel nut a material carcinogenic for oral tissues have not been successful5,6, possibly because extracts were prepared with solvents in which the carcinogenic materials were not soluble. We have therefore extracted betel nut, alone or in combination with cured tobacco, with dimethyl sulphoxide (DMSO) and applied the extracts in this vehicle. Our choice of DMSO was based on the evidence that it is an excellent solvent with a low toxicity7, that it has great powers of penetration8 and that it enhances the absorption of various drugs through skin and mucous membranes without apparently affecting their pharmacological properties9–12. Furthermore, the use of DMSO as a vehicle decreases the latency period for the production of oral tumours in hamsters with dimethylbenzanthracene13–14. We have found that repeated, topical applications of DMSO extracts of betel nut to the mucosa of the buccal pouch of hamsters result in the development of leukoplakia and tumours. The incidence of tumours increases when the extract is made from a mixture of betel nut and cured tobacco, although extracts of tobacco alone cause leukoplakia but not tumours.

Carcinogenic Effect of a Dimethyl Sulphoxide Extract of Betel Nut on the Mucosa of the Hamster Buccal Pouch

Dimethyl sulfoxide (DMSO) is becoming increasingly popular as a vehicle in studies employing central injections. The aim of the present study was to determine whether the vehicle required for solubilization of substances for central injection [75% DMSO and 25% artificial CSF (aCSF)] would alter the well-characterized stimulatory response to norepinephrine (NE) injected into the paraventricular nucleus (PVN) on short-term food intake. To evaluate its suitability, we compared the effects of repeated unilateral injections of NE dissolved in two different vehicles (100% aCSF or 75% DMSO, 25% aCSF), in separate groups of animals every 48 h over a 30-day period. NE (40 nmol) stimulated food intake by approximately sevenfold compared to either vehicle alone, and the stimulatory effect was similar whether aCSF or 75% DMSO was used as a vehicle. Furthermore, the NE-induced feeding did not vary in magnitude across a series of 13 tests. These results suggest that 75% DMSO is a suitable vehicle for administering NE (and likely other water-insoluble substances)in small volumes of 0.3 microl into specific brain regions.

DMSO as a vehicle for central injections: tests with feeding elicited by norepinephrine injected into the paraventricular nucleus.

Numerous research papers have reported and reviews have correlated results of studies on various aspects of the mammalian toxicology of pesticides.1 The interaction of pesticides with various other factors which might modify their toxic effect has received less consideration. These pesticide interaction phenomenona have been the subject of a recent symposium.2 However, no general review of the subject of pesticide interaction effects has yet been published.

The interaction of pesticides with other factors.

Dimethyl sulfoxide (DMSO).

SummaryThe lethality of a number of drugs dissolved in DMSO or saline has been compared. In no case was there a significant increase in drug lethality when administered with DMSO. Preliminary tests failed to indicate that DMSO possesses local anesthetic or analgetic action. DMSO also failed to alter the CSF or tissue penetration of PAH. DMSO appears to be a very good solvent with little or no effect on pharmacological action.

Apparent lack of interaction between dimethyl sulfoxide (dmso) and a variety of drugs.

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Apparent lack of interaction between dimethyl sulfoxide (dmso) and a variety of drugs.