Registration Dossier

Administrative data

Description of key information

There are studies on skin and eye irritation of dibutyl ether available, which were performed according to standard guidelines and GLP.

Key value for chemical safety assessment

Skin irritation / corrosion

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

Eye irritation

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

Respiratory irritation

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

Additional information

Skin Irritation

Studies in Animals

In a GLP patch test according to EC guideline B.4. (1992) and OECD TG 404 (2002), dibutyl ether (purity > 99.3 %) was only slightly irritating to the skin of 3 male rabbits after a 4-hour semi-occlusive exposure. During the observation time a very slight erythema (barely perceptible, grade 1) was observed in all three rabbits 60 minutes and 24 hours after patch removal. In two animals the very slight erythema persisted until 72 hours after patch removal. A very slight edema (barely perceptible, grade 1) was observed in two animals 60 minutes after patch removal. All symptoms were reversible within 4 days after patch removal. The mean Draize scores of the 24, 48, and 72 hour readings for erythema were 1.0, 1.0, and 0.3 for the three test-animals, respectively, and for edema 0.0 for all three test-animals (Degussa AG, 2005a).

Eye Irritation

Studies in Animals

In a GLP study performed in accordance with EC guideline B.5. (1992) and OECD TG 405 (2002), the mean Draize scores of the 24, 48 and 72 hour readings after the instillation of 0.1 ml dibutyl ether (purity > 99.3 %) into the conjunctival sac were 0.0 regarding iris lesions, conjunctival redness, and conjunctival chemosis in all three male rabbits. Regarding corneal opacity the mean score was also 0.0 in two of the three test-animals and 0.3 in one rabbit. Opacity of grade 1 (scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible) was observed in two animals 1 hour after instillation. In one of these two animals the slight opacity persisted until 24 hours after instillation. The fluorescein test performed 24 hours after instillation of the test item revealed corneal staining of one quarter of the surface in this animal. Irritation of the iris of grade 1 (markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)) was observed in one animal 1 hour after instillation. Conjunctival redness of grade 1 (some blood vessels definitely hyperemic (injected)) was observed in all three test-animals 1 hour after instillation. No changes, as compared to the untreated control eyes, were visible at 48-hours and 72-hours readings in any of the three test animals. The test substance produced no corrosion or irreversible effects in any of the animals (Degussa AG, 2005b).

Studies in Humans

In a study on sensory response to dibutyl ether, 200 ppm (corresponding to 1066 mg/m³) dibutyl ether were described as irritating to the eyes of a majority of 12 volunteers exposed in a gas cabinet to the substance for a period of 15 minutes (Silverman, Schulte and First, 1946). Based on the method described in another publication (Nelson et al., 1943) the authors didn’t differentiate between toxic and sensory effects (unpleasant, not necessarily toxic effects), therefore irritating doesn’t mean necessarily primary irritating effects.

 

Respiratory Tract Irritation

Studies in Animals

Rats exposed nose-only to 150, 500, or 1500 mg dibutyl ether/m³ 6 hours/day, 5 days/week for four weeks showed no clinical sign of respiratory tract irritation and no exposure-related histopathologic changes in the respiratory tract (for detailed study description see TNO, 2005).

Studies in Humans

In a study on sensory response to dibutyl ether, 200 ppm (corresponding to 1066 mg/m³) dibutyl ether were described as irritating to the eyes and nose, but not to the throat of a majority of 12 volunteers exposed in a gas cabinet to the substance for a period of 15 minutes (Silverman, Schulte and First, 1946). Based on the method described in another publication (Nelson et al., 1943) the authors didn’t differentiate between toxic and sensory effects (unpleasant, not necessarily toxic effects), therefore irritating doesn’t mean necessarily primary irritating effects.

Justification for classification or non-classification

Dibutyl ether is only very slightly irritating to the skin and the eyes of rabbits, as determined in GLP studies performed in accordance with OECD TG 404 and 405, respectively. All symptoms of irritation were completely reversible within 96 and 48 hours, respectively. In humans, a 15 minutes exposure towards 200 ppm (corresponding to 1066 mg/m³) dibutyl ether was reported to be sensory irritating to the eyes and the nose, but not to the throat. In a 28-day inhalation GLP study, performed according to standard guidelines, dibutyl ether at concentrations of up to and including 1500 mg/m³ was not irritating to the respiratory tract of rats. Therefore, the substance does not need to be classified and labelled for irritation, according to the Regulation 1271/2008 and the Directive 67/548/EEC.