Registration Dossier

Toxicological information

Health surveillance data

Currently viewing:

Administrative data

health surveillance data
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
Lack of nephrotoxicity of intravenous dimethylsulfoxide
Bennett WM and Muther RS
Bibliographic source:
Clinical Toxicol. 18, 615-618
Reference Type:
Lack of Nephrotoxicity of Dimethyl Sulfoxide in Man And Laboratory Animals
Bennett WM, Bristol T, Weaver WJ and Muther RS
Bibliographic source:
Ann. NY Acad. Sci., 411, 43-47

Materials and methods

Study type:
human medical data
Endpoint addressed:
other: nephrotoxicity
Test guideline
no guideline followed
Principles of method if other than guideline:
The renal function of patients receiving DMSO (1000 mg/kg bw) was carefully observed before and after iv infusions.
GLP compliance:
not specified

Test material

Details on test material:
No data


Type of population:
other: patients with chronic stable neurologic deficits related to traumatic spinal cord injury.
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
Fourteen patients (12 men and 2 women) with a mean age of 28 years (18-48) were studied. All had chronic stable neurologic deficits related to traumatic spinal cord injury. None had a history of parenchymal renal disease but because of bladder dysfunction, lower urinary tract infections were common. DMSO 1 g/kg body weight in 5% dextrose water was administered intravenously for three successive days. Infusion times of the 10-40% solutions were variable, ranging from 10 minutes to 24 hours. Six patients received two or more separate courses of DMSO infusions.
Blood urea nitrogen, serum creatinine, and 12-hour creatinine clearances were measured before and after each DMSO infusion. Urinary sediment examinations were performed before and after each infusion. Hematocrit, reticulocyte count, total/indirect bilirubin, lactic acid dehydrogenase, free hemoglobin, and serum haptoglobin were also noted. Urine was qualitatively assayed for hemoglobin and myoglobin and if positive, the pigment was characterized by electrophoresis. Statistical differences in renal function were examined by a paired t test.

Seven additional patients (5 men and 2 women) with a mean age of 24 (17-36) had 24-hour urines collected before DMSO and on each infusion day for creatinine and β-2 microglobulin. The latter was determined by. All samples were alkalinized with 1 N sodium hydroxide to prevent microglobulin degradation prior to assay and were run in duplicate. Differences in excretion were analyzed by a paired t test.

Results and discussion

No change from baseline in the blood urea nitrogen, serum creatinine, or creatinine clearance was observed after three days of 1000 mg/kg DMSO infusions. This was the case independent of the concentration of DMSO or the duration of infusion. In the six patients who had additional series of three infusions on separate occasions over 2-6 months, there was no decline in creatinine clearance or elevation of serum creatinine. No patients had urinary sediment abnormalities despite hemoglobinuria. Specifically, there was no increase in qualitative urine protein or glucose and no decrease in first morning specific gravity. Most patients were free of microscopic hematuria and on no occasion did the number of red blood cells per high power field increase over baseline values.

Minutes after each infusion with 20-40% DMSO was begun, reddish discoloration of the urine appeared which persisted for 2-4 hours after the drug was stopped. With 10% infusions the urine was only occasionally pink-tinged. However, qualitative tests for hemoglobinuria were commonly positive even in patients without changes in urine color. Hemoglobin was confirmed by electrophoresis in all cases where the qualitative test was positive. Myoglobin was absent.. Total and indirect bilirubin only changed significantly with 20 and 40% infusions and rose 1.6 and 1.2 mg%, respectively.

Urinary β-2 microglobulin excretion did not change significantly over the course of the three infusions. Mean of baseline values was 92.6 µg/l. At 24 hours it was 30.8 µg/l, at 48 hours 79.8 µg/l, and at 72 hours 128.8 µg/1. The normal range in the laboratory is 4-375 µg/l.

Any other information on results incl. tables

Table 1: Renal functional parameters before and after three days of 10-40% DMSO (1000 mg/kg)




16 ± 2

17 ± 3


Serum creatinine (mg/dl)

0.7 ±.03

0.7 ±.02

p - NS

Creatinine clearance (ml/min)

123 ± 10

128 ± 12

p - NS

N = 14

Table 2: Hemolysis after DMSO infusions



Δ Free Hb (mg/dl)

Δ Serum Haptoglobin (mg/dl)

















Applicant's summary and conclusion

No decrease in renal function was observed in a group of patients receiving DMSO as experimental therapy for stable spinal cord injuries.
Executive summary:

DMSO administered intravenously can protect experimental animals with massive stroke and brain swelling from mortality and neurologic impairment. Studies in patients suffering from cerebral trauma also suggest considerable efficacy. Intravenous DMSO was used to treat seven patients with stable spinal cord injuries. Because of drug-associated hemoglobinemia and hemoglobinuria, the patients were studied for subtle evidence of renal tubular dysfunction by serial measurements of urinary beta-2-microglobin excretion. No increases in tubular protein excretion or decreases in glomerular filtration rate were observed following short-term infusions of 10-40% DMSO (1000 mg/kg bw). No significant short-term nephrotoxicity was observed from intravenous DMSO.