Registration Dossier

Administrative data

Description of key information

SKIN IRRITANCY: 3 key studies. Some variability in degree of acute irritation (slight to severe experience, but primarily erythema rather than odema) characterised by persistency and very slow disappearance of effects.
EYE IRRITANCY: 1 key study and 10 reliable supporting studies: All consistency conclude that 2-butoxyethanol is irritant. Lesions characterised particularly by conjunctival reaction (redness) and persistence of effects.

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

A number of reliable skin irritation studies have been performed. These consistently show that 2 -butoxyethanol causes moderate irritation to severe irritation (primarily manifest as erythema but also oedema) when applied occlusively on the skin for a period of up to 24 hours. The irritant effects are particularly slow to recover, with erythema persisting for up to 14 days and beyond.

EYE IRRITATION

A number of studies have been performed to assess the eye irritation properties of 2 -butoxyethanol (2BE) . Not all have been performed according to guidelines, particularly regarding observation periods, but overall, the studies consistently record that 2BE is irritant or severely irritant to the eyes of rabbits with effects on iris and cornea and particularly conjunctivae. In one well performed study 2BE produced irreversible effects on the conjunctivae and on the cornea in at least one treated rabbit. However, this study was performed according to the old guideline. In the current guideline, it is possible to rinse the treated eye for animal welfare purposes and to more closely simulate the human situation where lachrymation would clear the substance from the eye. In a GLP test, performed according the recent guidelines, 2BE was only irritant (R36) as all symptoms reversed within 21 days. In other respects, the studies produced similar results. It was also demonstrated that dilution of 2BE in water decrease its irritant properties to the extent that a 70% solution did not produce the level of corneal swelling that had been correlated with the classification threshold for R36.

RESPIRATORY IRRITATION

There are no specific studies on this end point recorded here. Chapter 7.9.3 records a study by Kane where sensory irritation was evaluated using an in vivo method with mice (Kane, 1980). In an animal study, mice were exposed to 2 -butoxyethanol to assess the suppression of respiratory rate with increasing vapour concentration to enable the calculation of the RD50 (50% depression) as a measure of sensory irritation. The response obtained within the 150 -1500ppm concentration range tested was less than a 50 % decrease in respiratory rate, ie a relatively shallow dose response curve was obtained. The RD50 calculated by extrapolation was 2825 ppm, a value well in excess of the saturated vapour pressure. This was in excellent correlation with a QSAR model for RD50 generated at a later date, which predicts a value of 2818ppm. When compared with the author's criteria of evaluation, 0.01 RD50 (about 28 ppm) would cause minimal or no sensory irritation whereas 0.1 RD50 (about 280 ppm) would cause definite but tolerable sensory irritation.

Human volunteer studies are reported elsewhere. Three volunteers were exposed to 100 and 200 ppm of 2 -butoxyethanol for periods of up to 4 hours (Mellon institute, chapter 7.10.3)). Immediate irritation of the nose and throat, followed by ocular irritation and disturbed taste was reported by all three subjects Whether such ‘irritation’ was physiological or merely discomfort is not clear.

In other human volunteer inhalation studies (Johanson 1986, Kumagai, 1999 - chapter 7.1.1) 2 -butoxyethanol was not irritant to the eyes or respiratory tract at doses of 20 ppm for 2 hours or 25 ppm for exposure periods of 10 minutes. In a more recent study (Jones, 2003 -chapter 7.1.2) four volunteers reported no signs of irritation were reported after exposure to 50 ppm 2 -butoxyethanol for 2 hour periods on multiple occasions.

Ovarall the available informatin in both animals and humans does not indicate that 2 -butoxyethanol has any significant potential for respiratory irritation. No classification is required for this end point.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

SKIN IRRITATION

Because of the nature of the irritant response and the slow recovery time of effects seen in animals, 2 -butoxyethanol can be considered to be a skin irritant. Classification R38 is needed under the DSD and as a category 2 skin irritant under the EU GHS regulation.

EYE IRRITATION

The general response is similar to skin irritancy, with the actual effects sometimes not being severe enough to even trigger an irritancy classification but the effects are quite persistent. However, from the data available, it appears that this persistency is related to whether the eyes are washed or not. In the GLP study to the current protocol where the eyes were washed after 24 hours, full recovery occured. This situation is considered more representative of the hazard to and likely response of humans. On this basis, the more recent result should therefore be given precedence and a classification of R36 under the DSD and a category 2 eye irritancy classification under the EU GHS regulation is warranted.

RESPIRATORY IRRITATION

No data indicating a classification should be considered.