Registration Dossier

Toxicological information

Repeated dose toxicity: other routes

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Subacute toxicity of intravenous dimethyl sulfoxide in rhesus monkeys
Author:
de la Torre JC, Surgeon JW, Ernest T, Wollmann R
Year:
1981
Bibliographic source:
J. Toxicol. Environ. Health, 7 (1), 49-57

Materials and methods

Principles of method if other than guideline:
Method: other: no data
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test compound: Dimethylsulfoxyde
CAS no.: 67-68-5
Source: Research Indistries, Salt Lake City, Utah
Batch : no data
Purity : 100% pyrogen free

Test animals

Species:
monkey
Strain:
other: Macaca mulatta (rhesus)
Sex:
male
Details on test animals and environmental conditions:
Wieght: 3-6 kg

Administration / exposure

Route of administration:
intravenous
Vehicle:
physiological saline
Duration of treatment / exposure:
9 days consecutive
Frequency of treatment:
1 x per day
Doses / concentrations
Remarks:
Doses / Concentrations:
3 and 2 g/kg
No. of animals per sex per dose:
6 males
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: 120 days
Daily i.v. doses of 3 or 2 g/kg DMSO in a 40% solution were given respectively to 4 or 1 male rhesus monkeys for 9 consecutive days.

Examinations

Observations and examinations performed and frequency:
The monkeys were monitored before and after treatment for 4 months for changes in blood chemistry, haematology, urine, and ocular, neurological, and cardiovascular systems.
At the end of the study all animals were sacrificed and gross and microscopic pathological examinations were performed.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
The blood chemistries, urinalysis, haematology, and ophthalmologic and gross and histological examinations of tissues in the DMSO animals were not significantly different from those in the control monkey.

The rapid four-fold increase in diuresis over the control values in the monkeys receiving 2 or 3 g/kg DMSO supports previous results. This urine output indicates that DMSO is one of the strongest diuretics known. The absence of any microscopic or gross structural damage to the kidneys suggests that the coffee-colored urine seen after DMSO administration represents a transient erythrocytic hemolysis, possibly caused by an osmotic gradient due to DMSO in the vascular system. Since this effect was short lived and did not significantly alter the red cell count or the haemoglobin and hematocrit values, the coffee-colored urine represented a transient and reversible condition.

The partial thromboplastin time in DMSO treated monkeys decreased from a normal mean of 46 s to a mean of 18.7 s. These values returned to normal when DMSO administration was stopped. Although the PT values in both saline and DMSO treated monkeys fluctuated slightly before and after treatment, the values did not significantly differ from the control standard range. By contrast, the PTT values in both DMSO and saline treated animals were abnormal even before treatments began and remained that way after treatment.
An increase in respiratory rate after DMSO was previously reported. It appears from these studies that DMSO acts as a central respiratory stimulant when given iv in bolus form. A rise in minute respiratory volume concomitant with the rise in respiratory rate was also reported.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

These data indicate that monkeys receiving a total of 108-127g 40% DMSO or equal saline volumes iv during a 9-d study showed no significant or adverse changes in the chemical and physiological parameters studied. No gross or microscopic pathology was found in any monkey at the end of the 4-mo observation period.

Applicant's summary and conclusion