Registration Dossier

Administrative data

Description of key information

A skin irritation assay performed in rabbit according to the OECD guideline # 404 revealed no more than a very slight or well-defined erythema, which disappeared in 3 days. In humans, repeated application of DMSO solution for up to several months can induce transient erythema, burning, stinging and itching, which returned to normal after discontinuation of treatment.
DMSO is slightly irritating for the eye. In studies performed following the OECD guideline # 405 or the EEC method B.5, a slight to moderate conjunctival irritation, which cleared in 3 days, was observed in the eyes of rabbits. A repeated instillation (100% DMSO, 3 times/day for 6 months) in the eyes of rabbits induced only a temporary lacrimation but show any changes in the iris, cornea, lens, retina, conjunctiva and lids In humans, the instillation of solutions containing 50 to 100% DMSO has caused transient sensation of burning which was reversible within 24 hours.
Repeated exposure to DMSO vapors didn’t cause any irritation to the respiratory tract, however the exposure to high concentrations in the form of an aerosol induced an irritation of the upper airways after a repeated exposure.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

The skin irritation potential of DMSO has been investigated in a rabbit study compliant with the OECD guidelines. Additional non-guideline studies are available in rabbits, guinea pigs and mice. Clinical studies performed with different DMSO concentrations and durations of administration are also available.

Studies in Animals

In a test performed in rabbits according to OECD guideline # 404, a 4-hour application of pure DMSO under a semi-occlusive dressing induced a very slight or well-defined erythema on day 1 in all animals, which persisted until day 2 in one animal and until day 3 in another one. The mean scores over 24, 48 and 72 hours for each animal were 0.3, 0.0 and 0.7 for erythema and 0.0, 0.0 and 0.0 for edema (Sire, 2007).

In a test performed in rabbits according the method described by Draize, pure DMSO was applied topically for 24 hours. There was essentially no effect, other than a slight and rapidly reversible erythema (Fishman et al., 1969).

Pure DMSO was applied under an occlusive patch for 4 hours, to the intact skin of six hairless guinea pigs according to a modified Draize test. Cutaneous reactions were observed when the patches were removed and at, 24, 48, and 72 hours after application. Well-defined erythema and very slight oedema were exhibited 4 h following application. The mean scores for erythema were 1.9, 0.8, 0.1 and 0 at 4, 24, 48 and 72h, respectively, and the mean scores for oedema were 0.4 at 4h then 0 at any of the other scoring times. A rapid reversibility was observed thereafter, and all reactions cleared at 72 h (Tenjarla et al., 1995).

Undiluted DMS0 was painted on to the dorsal scapula region of 5 male AH mice twice a week for 30 weeks. At the end of the exposure period, no discernable effect on the skin was observed  (Brown et al., 1963).

Wright and Winer (1966) exposed male guinea pigs four times daily for 10 days to 63 applications to 0.5 mL full strength DMSO but results for irritation were not scored. Clinical signs consisted in erythema from day 2 of treatment, which was never severe, and edema from day 9, both being rapidly resolved. Nevertheless, it must be mentioned that continuous application also lead to dryness, scaling and thickening of the treated skin, which lasted until the end of the experiment; thickening was still present 6 months following the end of the experiment. Histopathologic findings showed a marked effect in the epidermis with hyperkeratosis and acanthosis occurring from the beginning and lasting throughout the experiment, supported by the week 9 of a hardening of the skin.

With an application of 3 to 4 drops of undiluted DMSO for 5 days to the back of guinea pigs, Kumar (1987) reported kind of same effects, without any score. Besides erythema, which started on the second day, increased on the fourth day, and for which there is no data on reversibility, a thickening was reported by day 3, as well as a dry and rough skin.

Studies in Humans

Kligman (1965) reported that an occlusive exposure to DMSO solutions of 30 to 70% for 1 hour didn’t cause clinical signs of irritation such as erythema or swelling. With 90% solutions, a papulo-vesicular reaction emerged almost invariably after 1 hour with edema of the skin and tiny, discrete, translucent vesicles, which yielded little or no water. Moreover death of the outer epidermis occurred with DMSO solutions of 50-90% and higher; the effect was followed by a rapid regeneration: clues of damage remained for 7 days but 48 hours following the exposure, new epidermal cells had been generated and within 4 days epidermal regeneration was complete, accompanied by mild acanthosis.

When occlusive exposure to 90% aqueous DMSO solution was performed in 9 subjects for 30-35 days, dermatitis occurred within 24 hours, increased for 12 days and gradually regressed. At the end of the experiment, the skin was generally non-reactive, except for little scaling or pigmentation change but histologically, there was some hyperkeratosis and moderate acanthosis (Kligman, 1965).

Rosenbaum (1965) observed sensation of warmth in 548 patients treated for 7 days to 10 months with daily application of 60 to 90% of DMSO solutions and sometimes erythema, itching & local urticaria. In most cases this local irritation disappeared within 2 or 3 hours.

Steinberg (1967), in a similar clinical study, observed slight skin effects following topical application of 90% DMSO solutions for up to 14 months in 500 subjects. In most cases, transient erythema, burning, stinging and itching were observed but became less intense or disappeared when the treatment was discontinued.

In human volunteers exposed to topical application of 100 % DMSO, Sulzberger et al. (1967) reported, in a significant proportion, many tiny follicular papules with an erythematous ring appearing within 5-15 minutes after application of a drop of 100% DMSO, followed 20-30 minutes later by a wheal which persisted for about 1 hour. In volunteers exposed to topical application of 80-90% DMSO, Sulzberger et al. also reported erythema in almost all cases. This reaction was observed frequently with 70% solutions and at lower concentrations, the irritation occurred less commonly. A difference in susceptibility was suggested to explain some reactions observed with 20% solutions. Histopathological examinations revealed epidermal changes similar to that which one notes after prolonged immersion in water or under occlusive dressings or wet compresses.

John and Laudahn (1967) performed single and short-term applications of 90% DMSO solutions over 1097 patients and observed local skin reactions in 91.9 % of the patients after repeated applications. A slight irritation, consisting of itching, warmth and transient erythema, occurred in 33.2% of patients and typical symptoms of irritation such as burning, stinging, erythema for 3-4 hours and occasional urticaria in 56.5% of patients. More severe reactions such as local dermatitis, urticaria and occasional vesiculation were present in only 2.2% of the subjects.  After several weeks of continuous applications, the epidermis showed some exfoliation and desquamation but was normal upon gross evaluation and these changes returned to normal within 2 weeks after discontinuation of treatment.

Eye irritation

The eye irritation potential of DMSO in rabbits has been investigated in studies compliant with the OECD guidelines and in a clinical study performed with different DMSO concentrations.

Studies in Animals

In a test performed by the French Health National Laboratory of the Medicine Agency following OECD Guideline # 405 (LNS, 1992), 0.1 mL of undiluted DMSO was instilled into the eyes of 3 rabbits. A slight to moderate conjunctival irritation, which cleared in 3 days, was observed. All the individual key scoring levels were low; the mean 24+48+72 h scores for each rabbit were 0.3, 0.7 and 0 for chemosis, 1, 1.7, 0.7 for redness, 0,0,0 for iris and 0, 0, 0 for cornea.

In the study of Conquet et al. (1977), pure DMSO instilled into the right eye of 6 rabbits produced slight irritation 2 hours after instillation: the total Draize score recorded at 2 hours was 8/110. The slight irritation observed was reversible within one day.

DMSO (99%) was tested in accordance to EEC directive 84/449/EEC (Jacobs and Martens, 1987). 0.1 mL of DMSO was instilled into one eye of each group of 6 rabbits and the ocular lesions observed for 7 days. DMSO produced slight erythema of the conjunctiva over the first 3 days of the study. The mean scores for the 6 rabbits over 24+48+72 h were 0 for chemosis, 0.95 for erythema, 0.11 for iritis and 0.06 for cornea.

A drop of DMSO in 10, 15, 30 and 100% strengths was applied 3 times/day for six months to the right eye of New-Zealand rabbits (the left eye served as control). Ophthalmoscopic, retinoscopic and intraocular pressure examinations did not show any changes in the iris, cornea, lens, retina, conjunctiva and lids between treated and control eyes of the same animal. Animals treated with drops of DMSO maintained essentially normal values for serum, lens and anterior aqueous humour and for soluble crystallins extracts. The only gross effect was temporary lacrimation in the eye receiving 100% DMSO (Wood et al., 1967).

Studies in Human

In humans, several investigators evaluated DMSO as a topical anti-inflammatory agent on the eye or as a solvent and carrier for ophthalmic drugs (Grant, 1986). In the study performed by Kligman (1965; reliability 2), aqueous solutions containing different concentrations of DMSO were instilled without washing into the lower conjunctival sacs of adult men. This treatment was without effect until concentration of 50%, at which point most subjects complained of transient burning. At 90%, all subjects experienced temporary stinging and burning, and a few exhibited mild injection of the conjunctival vessels. The eye was completely normal at 24 hours.

Respiratory tract irritation

No signs of respiratory tract irritation were observed in an acute inhalation toxicity study with DMSO (Jackson, 1998), rats were exposed to an aerosol concentration of 5.3 mg/l for 4 hours. As reported in section "repeated dose toxicity", exposure of rats to ca. 1 mg/L DMSO as vapors for up to 90 days didn’t cause any irritation to the respiratory tract (Kenny, 2000). Irritation in the upper airways (slight inflammation and hyperplasia in the nasal epithelium and pharynx), which was slowly reversible, was only observed when rats were exposed to a DMSO aerosol (Kenny, 1999 and 2000). These irritating effects can be related to the repeated deposit of the non-respirable fraction of the DMSO aerosol in the upper respiratory tract when the animals are exposed to very high concentrations. Based on these data, classification for respiratory tract irritation is not warranted according to EU Directive 67/584/EEC and EU regulation (EC) No 1272/2008 (CLP).


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Classification for skin, eye and respiratory tract irritation is not warranted according to EU Directive 67/584/EEC and EU regulation (EC) No 1272/2008 (CLP).