Registration Dossier

Administrative data

Description of key information

Skin: Highly irritating to corrosive.

Eyes: May cause irreversible 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:
adverse effect observed (irritating)

Additional information

Skin irritation/corrosion of 1,4 -Butynediol (B3D) has been examined in 3 well documented and reliable non-GLP OECD 404 guideline (or equivalent) studies, with results ranging from non-irritating (Jedrychowski, et. al., 1992) to irritating (BASF 1986) to mildly corrosive (Hüls AG, 1985). The reason for such variable results is not clear. In Jedrychowski, et. al. and in Hüls AG, solid B3D of reported purities of 99% or greater were applied to unabbraded shaved skin under occlusive conditions for 24 and 4 hours respectively, followed by rinsing in the the latter study and, respectively, followed by a 72 hour and a 14 day observation period. The primary differences in the two studies were the test animal (Vienna white rabbits vs. Russian white Chbb-SPF rabbits, respectively) and, in the case of Jedrychowski, et. al. the use water to pre-moisten the B3D prior to application. In the BASF study, an 80% aqueous solution was applied to unabbraded shaved skin of Vienna white rabbits under semi-occlusive conditions for 4 hours followed by an 8 day observation period. Given these variable results and lack of a clear explanation for the differences, considertion should also be given to experience in humans. Human patch testing has been conducted in two instances (Kligman, 1966 and GAF, undated) under non-GLP, non-guideline conditions with insufficient information reported to adequately judge reliability. Nonetheless, the results of both studies concluded that B3D, when applied to human skin and occluded for 48 hours and 5 days, respectively, caused "intense" reactions and severe erythema, but necrosis was not reported.

Eye irritation has been assessed in rabbits in two seperate non-GLP studies according to OECD Guideline 405, one study using 6 Russian white rabbits (Hüls AG, 1985) and the other using 3 Vienna white rabbits (BASF, 1986). Mean irritation scores for the individual test animals for the 24 to 72 hour time period were slightly higher in the Hüls AG study, with mean cornea scores of 5 of the test animals exceeding 1 and, in 1 of the 6 animals, effects on the cornea did not reverse within the 21 day observation period. Also in this study, mean conjunctival scores (redness) exceeded 2 for 4 of the 6 animals. In the BASF study, mean cornea and iris scores for the individual test animals for the 24 to 72 hour time period were <1 in all animals and conjunctival scores were <2 in all animals, with all effects fully reversing within 3 days.

Based on these results, B3D should be regarded as a skin and eye irritant, with the potential to be corrosive to the skin and to cause irreversible effects in the eyes.

Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: highly irritating

Effects on respiratory irritation: highly irritating

Justification for classification or non-classification

Skin irritation

Based on evidence of necrosis in the key study (Hüls AG, 1985) at 4 hours, but not at 3 minutes, 1,4 -Butynediol (B3D) should be classified as C; R34 (Causes burns) under the EU DSD criteria (EU Directive 67/548/EEC) and Corrosive, Category 1B under the EU CLP criteria (Regulation (EC) 1272/2008). These classifications are consistent with the official mandatory classifications given in Annex I of the directive and Annex VI of the regulation. 

Eye irritation

On the basis that 1,4-Butynediol (B3D) is classified as C; R34 (Causes burns), the risk of serious eye damage (Xi; R41) should be regarded as implicit. Based on results of the key study (Hüls AG, 1985), which produced mean irritation scores for 5 of the individual test animals for the 24 to 72 hour time period exceeding 1 and, in 1 of the 6 animals, effects on the cornea did not reverse within the 21 day observation period, B3D meets the criteria to be assigned Xi; R41 (Risk of serious damage to eyes) under the EU DSD criteria (EU Directive 67/548/EEC) and assigned Category 1 (Irreversible effects on the eye) under the EU CLP criteria (Regulation (EC) 1272/2008).

Respiratory irritation

Based on clinical observations of respiratory effects (irregular respiration) in rats exposed one time to B3D (vapour/aerosol mix) at a concentration of 0.26 mg/L for 4-hours (BG Chemie, 1996) and supported by pathology findings that included inflammatory as well as epithelial changes in the larynx following 5 days of exposure for 8 hours per day at a concentration of 0.027 mg/L (BG Chemie, 1997), B3D should be classified as Xi; R37 (Irritating to respiratory system under the EU DSD criteria (EU Directive 67/548/EEC) and Specific Target Organ Toxicity - Single Exposure (STOT-SE), Category 3 (Transient target organ effects) under the EU CLP criteria (Regulation (EC) 1272/2008).