Fusel oil

Endpoint summary

Description of key information

In conclusion, no acute toxicity hazard was 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 minor constituents of Fusel oil have no influence on the acute toxic properties. The available data from the main constituents of Fusel oil indicate that Fusel oil has no acute toxic properties, independent of the route of exposure. Based on the narcotic effects of 2-methylpropan-1-ol, Fusel oil is may also exhibit narcotic effects based on the composition.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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 acute toxicity study is available with the target substance Fusel Oil.

Acute oral toxicity

A study performed similar to OECD 401 is available for 2-methylbutan-1-ol (CAS No. 137-32-6) (BASF AG, 1979). Five Sprague-Dawley rats per sex and dose were treated by oral gavage with 1470, 2150, 3160, and 5000 mg/kg bw test substance. In the 5000 mg/kg bw dose group 3/5 males and 5/5 female animals were found dead within 1 day. In the 3160 mg/kg bw dose group 1 female animal died within 1 day. No mortality was observed in the 1470 and 2150 mg/kg bw dose groups. No effects on body weight changes were observed. Dyspnea, apathy, and staggering were observed in all dose groups, at least for 1 h after dosing. In the 2150, 3160 and 5000 mg/kg bw dose groups paresis/atonia, pain/corneal reflex absent, and a narcotic-like state were observed up to 5 h after dosing. In addition, a poor general state was observed in the 2150, 3160, and 5000 mg/kg bw dose groups. Gross pathology revealed no findings in the surviving animals. In dead animals acute congestive hyperemia in the heart and cardio dilatation were reported. In conclusion, a LD50 of 4172 mg/kg bw was calculated.

The key study on 3-methylbutan-1-ol (CAS No. 123-51-3) was performed similar to OECD 401 (BASF AG, 1979). Five Sprague-Dawley rats per sex and dose were treated by oral gavage with 2150 and 5000 mg/kg bw. In the 5000 mg/kg bw dose group 1/5 female animals died within 24 h. In the 2150 mg/kg bw dose group 1/5 female animals died within 48 h. No effects on body weight changes were observed within the 14-day observation period. Dyspnea, apathy, abnormal position, staggering, erythrodermia and poor general state were observed in all dose groups up to 5 hours after treatment. Rattling, atonia, paresis of forelimbs, salivation and lacrimation were also observed up to 5 hours after treatment in the 5000 mg/kg bw dose group. Gross pathology revealed no findings in the surviving animals. In dead animals acute congestive hyperemia in the heart and cardio dilatation were reported. In conclusion, a LD50 of > 5000 mg/kg bw was calculated.

For 2-methylpropan-1-ol (CAS No. 78-83-1) an available study was performed according to OECD guideline 401 (UCC, 1993). Five female Sprague Dawley rats were treated with 1000, 2000, 2830 and 4000 mg/kg bw 2-methylpropan-1-ol. In addition 3 males were dosed with 2830 mg/kg bw 2-methylpropan-1-ol. An acute oral LD50 value of >2830 and 3350 mg/kg bw was reported for male and female animals, respectively. Clinical signs included sluggishness, unsteady gait, lacrimation, piloerection, slow breathing, and prostration. Traces to large amounts of blood were found in the urine.

The key study for ethanol (64-17-5) was performed according to OECD 401 (Winters and Huges, 1976). Five Cox CD rats per sex and dose were treated by oral gavage with 8200, 9840, 11480, and 16070 mg/kg bw. No mortality was observed in the low dose group, whereas 3/10, 8/10, and 10/10 animals were found dead in the 9840, 11480, and 16070 mg/kg bw group, respectively. No effects on body weight changes were observed within the 14-day observation period. Decrease in motor activity and respiratory rate, gripping and ataxia were observed in all dose groups. In addition a moderate pupillary response was observed in the 9840, 11480, and 16070 mg/kg bw groups. Gross pathology revealed no findings in any animal. In conclusion, a LD50 of 10470 mg/kg bw was calculated. This is in concordance with the results of several available studies, where LD50 values ranging from 6160 to 17750 mg/kg bw were reported.

In conclusion, no acute oral toxicity hazard was observed with the main 4 constituents of Fusel oil. Acute oral LD50 values of > 2000 mg/kg bw were observed with all 4 substances. The minor constituents of Fusel oil do not influence the acute toxic properties of Fusel oil as they either have no toxic properties or are contained in small concentrations only, not affecting the hazard assessment of Fusel oil. The available data from the main constituents of Fusel oil indicate that Fusel oil has no acute toxic properties after oral exposure.

Acute inhalation toxicity

An acute inhalation study performed similar to OECD 403 is available for 2-methylbutan-1-ol (CAS No. 137-32-6) (BASF AG, 1979). Three Sprague-Dawley rats per sex and dose were whole-body exposed to a vapour-aerosol mixture of 12.8 or 16.61 mg/L for 7 h. No deaths were observed when animals were exposed to an atmosphere saturated with the test substance in 2 successive experiments. No effects on body weight changes were observed. Gross pathology revealed no findings in any animal. Intermittent respiration and attempts to escape were observed during the first 10 minutes of exposure. No further effects were observed within the 14-day observation period. In conclusion, a LC50 of > 16610 mg/m³ air was calculated.

A study performed similar to OECD 403, is available for 3-methylbutan-1-ol (123-51-3) (BASF AG, 1979). Six Sprague-Dawley rats per sex and dose were whole-body exposed to a vapour-aerosol mixture of 11.05 mg/L for 7 h. No deaths were observed when animals were exposed to an atmosphere saturated with the test substance. No information on body weight was given. Gross pathology revealed no findings in any animal. Loss of pain reflex up to 4 hours after the exposure start and intermittent respiration during the first 8 minutes of exposure were observed in the animals. No further adverse effects observed within the 14-day observation period. In conclusion, a LC50 of > 11050 mg/m³ air was deduced.

A study performed similar to OECD 403 is available for 2-methylpropan-1-ol (CAS No. 78-83-1) (Smyth, 1954). Three Sherman rats per sex and dose were exposed to a vapour of 24600 mg/m³ 2-methylpropan-1-ol for 4 h. 2/6 animals died. No details on body weight, clinical signs, and gross pathology were reported. In conclusion a LC50 of approximately 24600 mg/m³ air was calculated. Furthermore, in rats LC50 values in the range of ≥ 6500 to ≥ 21100 mg/m³ were reported for 2-methylpropan-1-ol (OECD, 2004a). In addition, LC50 values of 19900, 15500, and 26250 mg/m³ were reported for guinea pigs, mice, and rabbits, respectively (OECD, 2004a).

A study performed similar to OECD 403 is available for ethanol (CAS No. 64-17-5) (BASF AG, 1980). Ten Sprague-Dawley rats per sex and dose were nose/head-only exposed to a vapour of 62, 79.1, 93.4, 115.4, 155 mg/L ethanol for 4 h. No deaths were observed in the 62 mg/L exposure group, whereas 1/20, 2/20, 8/20, and 16/20 animals died in the 79.1, 93.4, 115.4, and 155 mg/L exposure groups, respectively. The body weight of males in higher dose groups was slightly decreased (no further details given). From 79.1 mg/L upwards the following clinical signs were observed: attempts to escape, reddish-watery eyes, nasal secretions, closing of eyelids, snout wiping, intermittent respiration, loss of pain reflex, narcosis, ruffled fur-coat and squatting position. The surviving animals were free from symptoms after day 1 until the end of observation period. Gross pathology revealed acute dilation and hyperemia in heart in the deceased animals. In addition, lungs showed partly acute flatulence of middle grade. Lungs were partly spotted, infracted, blood-filled and edematous. No abnormalities were observed in the sacrificed animals. No further adverse effects were observed within the 14-day observation period. In conclusion, LC50 values of 116.9 and 133.8 mg/L air were calculated for males and females.

Further studies on ethanol (CAS No. 64-17-5) reported LC50 values of 52.9 mg/L in rat after 6 h inhalation (BASF AG, 1980) and 114 mg/L in mice after 1 h inhalation (Moser and Balster, 1985).

In conclusion, no acute inhalation toxicity hazard was observed with the main 4 constituents of Fusel oil. LC50 values of > 11500 mg/m³ were observed with all 4 substances. The minor constituents of Fusel oil do not influence the acute toxic properties of Fusel oil as they either have no toxic properties or are contained in small concentrations only, not affecting the hazard assessment of Fusel oil. The available data from the main constituents of Fusel oil indicate that Fusel oil has no acute toxic properties after inhalation exposure.

Acute dermal toxicity

When primary amyl alcohol, containing 32-38% 2-methylbutan-1-ol (CAS No. 137-32-6), was applied to the clipped abraded skin, the LD50 in rabbits was greater than 3160 mg/kg bw, the highest dose administered. Signs of irritation at the site of application of included slight to moderate erythema, desquamation, necrosis, and eschar. Signs of toxicity included labored respiration, ataxia, and sprawled limbs; recovery occurred with 4 to 48 hours (OECD, 2006).

For 3-methylbutan-1-ol (CAS No. 123-51-3) the available study was performed according to a method from Smyth HF et al. (1962) (Smyth et al., 1969). Four male rabbits were treated with the neat test substance (no dose given) for 24 h under occlusive conditions. A LD50 of approximately 3216 mg/kg bw was reported. No further details on mortality, clinical signs, body weight or gross pathology were reported.

For 2-methylpropan-1-ol (CAS No. 78-83-1) an available study was performed according to OECD guideline 402 (UCC, 1993). Five female New Zealand White rabbits were exposed to 1000, 2000, and 5000 mg/kg bw 2-methylpropan-1-ol for 24 h under occlusive conditions. In addition 3 male rabbits were treated similarly with 2000 mg/kg bw 2-methylpropan-1-ol. 0, 1, and 5 animals died after exposure to 1000, 2000, and 5000 mg/kg bw 2-methylpropan-1-ol. None of the male rabbits died. The dermal LD50 values for isobutanol was therefore > 2000 mg/kg bw for male rabbits and 2460 mg/kg bw for female rabbits. Signs of toxicity included sluggishness, prostration, labored breathing and red eyes, and erythema and necrosis at the application site. Skin lesions were still apparent after 14 days.

Supporting data for 2-methylpropan-1-ol indicate a LD50 of 3392 mg/kg bw (Smyth et al., 1969). Four male rabbits were treated with the neat test substance (no dose given) for 24 h under occlusive conditions. No further details on mortality, clinical signs, body weight or gross pathology were reported.

For ethanol (CAS No. 64-17-5) a low dermal acute toxicity can be assumed. Treatment of 4 rabbits with a single dose of 15800 mg/kg bw ethanol resulted in the death of 1 animal. Thus, the LC50 was > 15800 mg/kg bw (OECD, 2004b). Ethanol possesses poor skin absorption, which is in accordance with the high LD50 value (Pendlington, 2001).

In conclusion, no acute dermal toxicity hazard was observed with the main 4 constituents of Fusel oil. LD50 values of > 2000 mg/m³ were observed with all 4 substances. The minor constituents of Fusel oil do not influence the acute toxic properties of Fusel oil as they either have no toxic properties or are contained in small concentrations only, not affecting the hazard assessment of Fusel oil. The available data from the main constituents of Fusel oil indicate that Fusel oil has no acute toxic properties after dermal exposure.

Narcotic effects

Ethanol (CAS No. 64-17-5), 3-methylbutan-1-ol (CA 123-51-3) and 2-methylbutan-1-ol (CAS No. 137-32-6) are not classified as STOT SE Cat 3 according Annex VI of regulation (EC) No 1272/2008. 2-methylpropan-1-ol (CAS No. 78-83-1) is classified as STOT SE Cat 3 with “H336: May cause drowsiness and dizziness”.

In the available acute toxicity studies exposure to ethanol (CAS No. 64-17-5), 3-methylbutan-1-ol (CA 123-51-3) and 2-methylbutan-1-ol (CAS No. 137-32-6) led to effects as loss of pain reflex (BASF AG, 1979; CAS No. 123-51-3), narcotic like state (BASF AG, 1979; CAS No. 137-32-6) or decreased motor activity and reflexes (Winters and Huges, 1976; CAS No. 64-17-5) indicating signs of narcotic effects.

Based on the fact that 2-methylpropan-1-ol is legally classified for STOT SE Cat 3 (H336), Fusel oil is supposed to have narcotic effects 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, no acute toxicity hazard was 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 minor constituents of Fusel oil have no influence on the acute toxic properties. The available data from the main constituents of Fusel oil indicate that Fusel oil has no acute toxic properties, independent of the route of exposure. Based on the narcotic effects of 2-methylpropan-1-ol, Fusel oil is expected to exhibit narcotic effects, dependent on the amount of 2-methylpropan-1-ol.

References

OECD (2006) SIDS Initial assessment report for SIAM 22. Primary amyl alcohol (mixed isomers). CAS No: 71-41-0; 137-32-6. UNEP Publications

OECD (2004a) SIDS Initial assessment report for SIAM 19. Isobutanol. CAS No: 78-83-1. UNEP Publications

OECD (2004b) SIDS Initial assessment report for SIAM 19. Ethanol. CAS No: 64-17-5. UNEP Publications

 

Justification for selection of acute toxicity – oral endpoint

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

Justification for selection of acute toxicity – inhalation endpoint

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

Justification for selection of acute toxicity – dermal endpoint

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

Justification for classification or non-classification

Based on available data from the main constituents of Fusel oil on oral, inhalation and dermal toxicity, Fusel oil does not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.

Narcotic effects

Directive 1999/45/EC

Fusel oil has to be classified for narcotic effects according to regulation 67/584/EEC (Xi, R67) when it contains ≥ 15% of 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.

Regulation EC/1272/2008

Fusel oil has to be classified for STOT SE (H336) according to regulation EC/1272/2008, 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.