Fusel oil

Endpoint summary

Description of key information

Irritating effects on the skin and severe damage to the eye were observed with the main constituents of Fusel oil, being ethanol (CAS No. 64-17-5), 3-methylbutan-1-ol (CA 123-51-3), 2-methylbutan-1-ol (CAS No. 137-32-6), and 2-methylpropan-1-ol (CAS No. 78-83-1). The available data from the main constituents of Fusel oil indicate that Fusel oil has skin irritating properties and may induce severe damage to the eye. In addition, Fusel oil may have irritating effects on the respiratory tract.

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

Fusel oil is a UVCB substance comprising a complex mixture of alcohols, aldehydes, esters and other substances. The constituents and their concentration ranges are known. Fusel oil contains 4 main constituents being above ≥ 10%. In total, the 4 main constituents account for ≥ 80% of all constituents. In order to fulfil the standard information requirements set out in Annex IX in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from surrogate substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from surrogate substances (grouping or read-across).

The physicochemical, toxicological and ecotoxicological properties of the main constituents of Fusel oil determine, to a great extent, the physicochemical, toxicological and ecotoxicological properties of Fusel oil itself. Therefore, having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, 1.5, of Regulation (EC) No 1907/2006, a read-across is appropriate as their physicochemical, toxicological and ecotoxicological properties are likely to be similar. A detailed justification for use of read-across is given in chapter 13 of the technical dossier.

In conclusion, hazard assessment was based on the main constituents, when no experimental data was available with Fusel oil itself. The main constituents are ethanol (CAS No. 64-17-5), 3-methylbutan-1-ol (CA 123-51-3), 2-methylbutan-1-ol (CAS No. 137-32-6), and 2-methylpropan-1-ol (CAS No. 78-83-1).

No study investigating skin and eye irritation is available with the target substance Fusel Oil.

Skin irritation

One Draize test is available for 2-methylbutan-1-ol (CAS No. 137-32-6) in Vienna White rabbits (BASF AG, 1979), performed according to Federal Register 38, No. 187, § 1500.41, 27029 (27/09/73). The test substance was applied to a 2.5 x 2.5 cm application site for 24 h under occlusive conditions. The skin was either intact or abraded and no washing was performed after the 24 h treatment, whereas the skin was washed with a 50% Lutrol solution after the 5 min and 2 hour treatment. Animals were observed for 8 days. Skin effects were recorded after 24, 48, 72 hours and at the end of the observation period and were graded as described in OECD test guideline 404. Erythema and edema mean scores were 2.4 and 2.1 after the 24 h treatment. These effects were not fully reversible within 8 days. Necrosis (partly spotted) was observed in 5/6 animals starting from the second day after exposure and was persistent (with gain in intensity) at the end of the observation period. All these observations were confirmed at necropsy (crust formation). In conclusion, 2-methylbutan-1-ol was irritating to the skin under the conditions of the test.

The available study on 2-methylpropan-1-ol (CAS No. 78-83-1) was performed according to OECD 404 (Hoechst AG, 1988). Three New Zealand White rabbits were treated with 0.5 mL 2-methylpropan-1-ol for 4 h under semi-occlusive conditions. After 30-60 min, 2 of 3 rabbits exhibited slight to marked erythema (grade 1 and 2 of max. 4, respectively); after 24 h marked erythema was observed in 2 of 3 rabbits and slight edema (grade 1) was observed in 1 rabbit, which were fully reversible within 48 hours. The skin of all three animals was dry and rough at the 48 and 72 h reading. Individual mean animal scores (24/48/72 hours) were 0, 0.67, and 0.67 for erythema and 0, 0, and 0.33 for edema, respectively. In conclusion, 2-methylpropan-1-ol was not irritating to the skin under the conditions of the test.

One Draize test is available for 3-methylbutan-1-ol (CAS No. 123-51-3) in Vienna White rabbits (BASF AG, 1979), performed according to Federal Register 38, No. 187, § 1500.41, 27029 (27/09/73). 0.5 mL of the test substance was applied to a 2.5 cm x 2.5 cm application site for 24 h under occlusive conditions. The skin was either intact or abraded and no washing was performed after the 24 h treatment. Animals were observed for 8 days. Skin effects were recorded after 24, 48, 72 hours and at the end of the observation period and were graded as described in OECD test guideline 404. Erythema and edema mean scores were 2.4 and 2.1 in the 24 h treatment. These effects were not fully reversible within 8 days. Necrosis was observed in 3 animals (in one animal after 72 hours), intense crust formation in the remaining 3 animals at the end of the observation period for intact application sites. Blotched necrosis (in 2 animals) and crust formation (in one animal) were already observable after 72 hours. All these observations were confirmed at necropsy. In conclusion, 3-methylbutan-1-ol was irritating to the skin under the conditions of the test.

Ethanol (64-17-5) was tested similar to OECD 404 and in compliance with GLP (Nixon, 1986). Five New Zealand White rabbits were treated with 0.2 mL ethanol for 24 h under occlusive conditions. After the 24-h exposure period the application sites were wiped. No erythema or edema reactions were observed in any animal at any time point. No other effects were observed. In conclusion, ethanol was not irritating to the skin under the conditions of the test.

Further data in human and animals indicate that ethanol had a little potential to cause skin irritation (Jacobs and Martens, 1992; Phillips, 1972; Basketter, 2004; Houben, 2006).

Eye irritation

One Draize test is available for 2-methylbutan-1-ol (CAS No. 137-32-6) in Vienna White rabbits (BASF AG, 1979), performed according to Federal Register 38, No. 187, § 1500.41, 27029 (27/09/73). 0.1 mL of the test substance was instilled in one eye each of 6 rabbits. No washing was performed and eyes were observed 24 h, 48 h, 72 h and 8 d after treatment. Slight opacity of the cornea, ciliary injections in the iris and effects on the conjunctivae including redness, swelling, and discharge were observed. Effects on the cornea and conjunctivae redness were still available at the end of the observation period (grade 1). The mean scores (24, 48, 72 h) were 1, 1, 1.9 for cornea, iris, and conjunctivae redness, respectively. In addition, scar formation of eyelids was observed in 2 animals 24 hours after treatment and in a total of 3 animals from day 2 up to the end of the observation period. In conclusion, 2-methylbutan-1-ol is irritating to the eye under the conditions of the test.

A study performed according to OECD 405 is available for 2-methylpropan-1-ol (CAS No. 78-83-1) (Hoechst AG, 1988). Three New Zealand White rabbits were treated with 0.1 mL 2-methylpropan-1-ol for 24 h with subsequent washing of the eye with sodium chloride solution. The eyes were observed 24 h, 48 h, 72 h and 14 d after treatment. Mean scores of 1, 0.33, 2.55, and 1.55 were observed for cornea, iris, conjunctivae, and chemosis, respectively. Cornea score was not fully reversible in 1/3 animals and conjunctivae score was not fully reversible in 2/3 animals. In conclusion, 2-methylpropan-1-ol caused serious eye damage.

In further studies effects on cornea and conjunctivae were reported, which were partly reversible within 8-21 days (BASF 1978; BASF, 1979; UCC, 1993) or which were fully reversible within 14 days (mean scores of 2.08, 1.09, 2.42, and 2.25 for cornea, iris, conjunctivae, and chemosis) (Ecetoc, 1998).

A study is available for 3-methylbutan-1-ol (CAS No. 123-51-3) performed according to Federal Register 38, No 187, § 1500.41, 27019 (1973; BASF, 1979). Six New Zealand White rabbits were treated once with 0.1 mL 3-methylbutan-1-ol without subsequent washing of the eye. The eyes were observed 24 h, 48 h, 72 h and 8 d after treatment. Mean scores of 1.1, 0.3, 2.8, and 1.1 were observed for cornea, iris, conjunctivae, and chemosis, respectively. Effects were not fully reversible in all animals (cornea (4/6), iris (1/6), conjunctivae (5/6), and chemosis (3/6)). Myosis (constriction of the pupil) was observed in 3 animals after 24 h, in 4 animals after 48 h and 5 animals after 72 h, but was reversible within 8 days. Ulceration (in 2 animals after 24 and 48 h, not reversible in one animal) and scar formation (in 2 animals after 48 h, in 3 animals after 72 h and in 4 animals at the end of the observation period) were also observed. In conclusion, 3-methylbutan-1-ol caused serious eye damage Cat 1 (causes serious eye damage).

A study is available for ethanol (CAS No. 64-17-5) performed according to OECD 405 (Ecetoc, 1998). Three New Zealand White rabbits were treated once with 0.1 mL ethanol without subsequent washing of the eye. The eyes were observed 24 h, 48 h, 72 h and 21 d after treatment. Mean scores of 1.1, 0.44, 2.1, and 1.3 were observed for cornea, iris, conjunctivae, and chemosis, respectively. Individual means of 1.33 and 1.66 for corneal opacity and 2.66 and 2.33 for conjunctival redness were observed in 2/3 animals. Cornea score and iris score were fully reversible within 4 days in all animals. Effects on conjunctivae and chemosis fully reversed within 14 days in all animals. In conclusion, ethanol is irritating to the eye.

Respiratory irritation

2-methylpropan-1-ol (78-83-1) is classified as STOT SE Cat 3 (H335: May cause respiratory irritation) according to Annex VI of regulation (EC) No 1272/2008.

In the available acute toxicity studies in animals, signs of intermittent respiration (ethanol and 3-methylbutan-1-ol ) and edema in the lung were observed (ethanol). Observations in humans indicate that 3-methylbutan-1-ol has irritating properties to the respiratory tract (Nelson et al., 1943). The reported data for ethanol and 3-methylbutan-1-ol are not sufficient to clearly link the effects to respiratory irritation as described in regulation (EC) No 1272/2008. 

Based on the harmonized classification of 2-methylpropan-1-ol for respiratory irritation, Fusel oil may induce respiratory irritation as well, based on the composition. According to regulation (EC) No 1272/2008 classification of mixtures for STOT SE Cat 3 is proposed when one classified constituent appears at concentrations of 20% or higher in the mixture, although exceptions are possible based on expert judgement.

Conclusion

In conclusion, irritating effects on the skin and severe damage to the eye were observed with the main constituents of Fusel oil, being ethanol (CAS No. 64-17-5), 3-methylbutan-1-ol (CA 123-51-3), 2-methylbutan-1-ol (CAS No. 137-32-6), and 2-methylpropan-1-ol (CAS No. 78-83-1). The available data from the main constituents of Fusel oil indicate that Fusel oil has skin irritating properties and induces severe damage to the eye. In addition, Fusel oil is supposed to have irritating effects on the respiratory tract.

Justification for selection of skin irritation / corrosion endpoint:

Most reliable data of the main constituents of Fusel oil were used for hazard assessment.

Justification for selection of eye irritation endpoint:

Most reliable data of the main constituents of Fusel oil were used for hazard assessment.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Eye irritation

Directive 1999/45/EC

Based on the data of the main constituents of Fusel oil, the registered substance meets the criteria to be classified for risk of serious damage to eyes (Xi, R41) according to directive 1999/45/EC, when the sum of 2-methylpropan-1-ol (CAS 78-83-1), propan-1-ol (CAS 71-23-8), butanol-1-ol (71-36-3), and ethyl lactate (CAS 97-64-3) ≥ 3%.

Based on the data of the main constituents of Fusel oil, the registered substance meets the criteria to be classified for eye irritation (Xi, R36) according to directive 1999/45/EC, when the sum of 2-methylpropan-1-ol (CAS 78-83-1), propan-1-ol (CAS 71-23-8), butanol-1-ol (71-36-3), and ethyl lactate (CAS 97-64-3) ≥ 5% - < 10% or the sum of butan-2-ol (78-92-2) + ethyl acetate (CAS 141-78-6) + acetaldehyde (CAS 75-07-0) + 2-furaldehyde (CAS 98-01-1) ≥ 20%.

Regulation EC/1272/2008

Fusel oil has to be classified for serious eye damage (H318) according to regulation EC/1272/2008, when it contains 2-methylpropan-1-ol (CAS 78-83-1), propan-1-ol (CAS 71-23-8), butanol-1-ol (71-36-3), and ethyl lactate (CAS 97-64-3) ≥ 3% in total.

Fusel oil has to be classified for eye irritation (H319) according to regulation EC/1272/2008, when it contains 2-methylpropan-1-ol (CAS 78-83-1), propan-1-ol (CAS 71-23-8), butanol-1-ol (71-36-3), and ethyl lactate (CAS 97-64-3) ≥ 1 - < 3% in total or the sum of [(10 x 2-methylpropan-1-ol (CAS 78-83-1)+ 10 x propan-1-ol (CAS 71-23-8) + 10 x butanol-1-ol (71-36-3)+ 10 x ethyl lactate (CAS 97-64-3)) + butan-2-ol (78-92-2) + ethyl acetate (CAS 141-78-6) + acetaldehyde (CAS 75-07-0) + 2-furaldehyde (CAS 98-01-1) ≥ 10%.

Skin irritation

Directive 1999/45/EC

Based on the data of the main constituents of Fusel oil, the registered substance meets the criteria to be classified for risk of skin irritation (Xi, R38) according to directive 1999/45/EC, the sum of 2-methylpropan-1-ol (CAS 78-83-1), 3-methylbutan-1-ol (123-51-3), 2-methylbutan-1-ol (CAS 137-32-6), butanol-1-ol (71-36-3), and 2-furaldehyde (CAS 98-01-1) ≥ 20%.

Regulation EC/1272/2008

Fusel oil has to be classified for skin irritation (H315) according to regulation EC/1272/2008, when it contains 2-methylpropan-1-ol (CAS 78-83-1), 3-methylbutan-1-ol (123-51-3), 2-methylbutan-1-ol (CAS 137-32-6), butanol-1-ol (71-36 -3), and 2-furaldehyde (CAS 98-01-1) ≥ 10% in total.

Respiratory irritation

Directive 1999/45/EC

Fusel oil has to be classified for respiratory irritation according to regulation 67/584/EEC (Xi, R37) when it contains ≥ 20% of 2-methylpropan-1-ol (CAS 78-83-1), butanol-1-ol (71-36-3), butan-2-ol (78-92-2), acetaldehyde (CAS 75-07-0), 2-furaldehyde (CAS 98-01-1), and ethyl lactate (CAS 97-64-3) in total.

Regulation EC/1272/2008

Fusel oil has to be classified for STOT SE (H335) according to regulation EC/1272/2008, when it contains ≥ 20% 2-methylpropan-1-ol (CAS 78-83-1), propan-1-ol (CAS 71-23-8), butanol-1-ol (71-36-3), butan-2-ol (78-92-2), ethyl acetate (CAS 141-78-6) in total.