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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).

Five healthy non-smoking volunteers (aged 22-53 years) were exposed for six hours to air containing ethanol at 250, 500 and 1000 ppm corresponding to 471, 942, 1884 mg/m³ (Nadeau et al., 2003). Volunteers were instructed to avoid ingestion of ethanol and coffee during the 24 and 12 h preceding the exposures, respectively. Some sensitive markers of neuromotor disturbance (including reaction times, body sway, hand tremour and rapid alternating movements) were measured before and after each exposure, which was separated by at least 24 hours to avoid accumulation of ethanol in the body. A statistically significant decrease in diadochokinesia velocity (maximum speed) and harmonic index (left hand), and increase in sway velocity (closed eyes), was seen in volunteers exposed to air containing ethanol at 500 ppm (about 942 mg/m³), when compared to pre-exposure measures. However, no statistically significant changes were seen at any other exposure concentration (including 1000 ppm). Therefore, the NOAEC for neuromotor effects of ethanol in this acute human volunteer study can be considered as 1884 mg/m³.

Results from a developmental neurotoxicity study in rats suggest that ethanol at a dose of 1 g/kg bw/day administered to dams during gestation and lactation produced growth and quantifiable behavioral changes in the offspring (Vaglenova and Petkov, 1988). In further studies treatment with ethanol (11000 and 16000 ppm) in males prior to mating and pregnant females during gestation did not induce adverse behavioural effects in offspring (Nelson et al., 1985).

Repeated exposures of rats and mice to several concentrations of 3-methylbutan-1-ol resulted in a depression in recorded activity (Frantik et al., 1994). Treatment of rats and mice with 6240 and 3490 mg/m³ 3-methylbutan-1-ol for 4 and 2 h, respectively, led to 30% depression in recorded activity of the animals.

In a subchronic vapour inhalation study, Sprague-Dawley rats were exposed to 786, 1044, and 7764 mg/m³ 2-methylpropan-1-ol 6 h/day, 5 days/week for 3 months. There were no differences between treated and control groups for any parameter evaluated by the functional observational battery at any time point in the study. Repeated measures of the total motor activity indicated that there were no effects on total motor activity level after repeated exposure to 2-methylpropan-1-ol. Likewise, there were no statistically significant effects between groups on the pattern of habituation at any time point (Li et al., 1999).

The available data on the 4 main constituents of Fusel oil indicate that they may cause transient narcotic effects, but no further neurotoxic effects. Thus, Fusel oil is supposed to be not neurotoxic.



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