Registration Dossier
Registration Dossier
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EC number: 202-490-3 | CAS number: 96-22-0
Endpoint summary
Administrative data
Description of key information
Overexposure to ketone vapours can evoke, progressively, irritation of the eyes, nose, and throat as well as neurotoxic symptoms such as nausea, vertigo, incoordination or narcosis in humans. For diethyl ketone the threshold for eye irritation was around 700 ppm, whereas the threshold for respiratory irritation was around 400 ppm in human volunteers.
Additional information
The classic symptoms in humans produced by an overexposure to aliphatic ketones include, progressively, irritation of the eyes, nose, and throat, headache, nausea, vertigo, incoordination, central nervous system depression, narcosis, and cardiorespiratory failure. Recovery is usually rapid and without residual toxic effects (Krasavage et al., 1981).
In a study by Douglas and Coe (1988) various concentrations of diethyl ketone were applied to the eyes of volunteers through tightly fitting goggles and, in separate experiments, to the lungs via a mouthpiece. The number of volunteers is not given in the publication.
Exposure to the eyes lasted for 15 seconds per concentration. Lung exposure was achieved by the inhalation of 10 breaths of 1 L of gas at a given concentration. Eye response was detected subjectively, lung response (narrowing of the respiratory passages) was measured objectively by plethysmograph and the threshold concentrations for no-response were determined. The threshold for eye irritation was around 700 ppm, whereas the threshold for respiratory irritation was around 400 ppm in human volunteers.
Human data on the structural analogue methyl ethyl ketone were summarized recently in the technical support document on the derivation of AEGLs (Anonymous, 2009): “…In a 4-hour study, 200 ppm was also judged unobjectionable by healthy volunteers (Dick et al., 1992). Additional behavioural and metabolism studies with human volunteers conducted at 200 and 400 ppm for 4 hours did not reveal either irritant or neurotoxic effects. The Dick et al. studies (1984, 1988, 1989, 1992) with exposures to 200 ppm for 4 hours found no exposure-related changes in performance on psychomotor and mood tests or incidences of irritation. A 4-hour exposure to 90-270 ppm caused minor disturbances in the conception of time (Nakaaki, 1974). Several recent clinical studies (Dick et al., 1992; Muttray et al., 2002; Seeber et al., 2002; Shibata et al., 2002) reported that MEK was associated with strong odour rather than irritation. ...Subjects with self-reported multiple chemical sensitivity found repeated 8-11 minute exposures to a concentration of 380 ppm practically non-irritating (Seeber et al., 2002). Some workers exposed to higher concentrations, up to 1000 ppm total ketones for unknown exposure durations, suffered central nervous system depression (Smith and Mayers, 1944), but dermal exposure to the liquid in addition to inhalation exposure most likely contributed to the effects.”
References
Anonymous (2009). Methyl ethyl ketone (CAS Reg. No. 78-93-3): Interim acute exposure guideline levels (AEGLs) for NAS/COT Subcommittee. November 2008. Interim 3: 02/2009.
Dick RB, Setzer JV, et al.(1984). Effects of acute exposure of toluene and methyl ethyl ketone on psychomotor performance. Int. Arch. Occup. Environ. Health 54, 91-109.
Dick RB, Brown WD, et al. (1988). Effects of short duration exposures to acetone and methyl ethyl ketone. Toxicol. Lett. 43, 31-49.
Dick RB, Setzer JV, et al.(1989). Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone.Br. J. Indust. Med. 46, 111-121.
Dick RB, Krieg EF, et al.(1992). Neurobehavioral effects from acute exposures to methyl isobutyl ketone and methyl ethyl ketone. Fund. Appl. Toxicol. 19, 453-473.
Krasavage WJ, O'Donoghue JL, Divincenzo DG (1981). Ketones. In: Clayton GD, Clayton FE. 1981. Patty's Industrial Hygiene and Toxicology, 3rd rev ed. John Wiley & Sons, p. 4709-4800.
Muttray AD, Jung D, et al. (2002). Effects of an external exposure to 200 ppm methyl ethyl ketone on nasal mucosa in healthy volunteers. Int. Arch. Occup. Environ. Health 75, 197-200.
Nakaaki K (1974). An experimental study on the effect of exposure to organic solvent vapor in human subjects. J. Sci. Labour 50, 89-96.
Seeber AC, van Thriel C, et al. (2002). Psychological reactions related to chemosensory irritation. Int. Arch. Occup. Environ. Health 75, 314-325.
Shibata E, Johanson G, et al.(2002). Changes in n-hexane toxicokinetics in short-term single exposure due to co-exposure to methyl ethyl ketone in volunteers. Int. Arch. Occup. Environ. Health 75, 399-405.
Smithand Mayers MR (1944). Study of poisoning and fire hazards of butanone and acetone.Bull.Dep. Labor 23, 174-176.
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