Methyl butyl ketone , toxicity

Mendell JR, Saida K, Ganansia ME, et al Toxic polyneuropathy produced by methyl -butyl ketone. Science 185 787-789, 1974... 

Allen N, Mendell JR, Billmaier DJ, et al Toxic polyneuropathy due to methyl -butyl ketone. Arch Neurol 32 209-218, 1975... 

Nonmetallic neurotoxins are frequently used in industry in manufacturing of chemicals and resins or as solvents. Some examples are hydrogen sulfide (which paralyzes specifically the nervous centers that control respiratory movement), carbon disulfide, -hexane, methyl -butyl ketone, and acrylamide. Exposure to all of these substances may occur through inhalation of vapors. In addition, carbondisufide and acrylamide may enter the system by dermal absorption. -Hexane and methyl -butyl ketone are not toxic by themselves but are activated by cytochrome P-450 to the neurotoxic hexanedione (CH3COCH2CH2COCH3). 

The solvent hexane causes a different type of neurotoxicity, involving swelling and degeneration of motor neurones. This leads to paraesthesia and sensory loss in the hands and feet, and weakness in toes and fingers. Hexane has been widely used in industry as a solvent, and there have been many cases of neuropathy reported from different parts of the world. The toxicity is due to the metabolite 2,5-hexanedione which arises by co-1 oxidation at the 2- and 5-positions to 2,5-hexanediol, and then further oxidation to the diketone (figure 4.9). The 2,5-hexanedione then reacts with protein to form pyrrole adducts. The v-diketone structure is important, as 2,3- and 2,4-hexanedione are not neurotoxic. Methyl -butyl ketone also causes similar neurotoxic effects and is also metabolized to 2,5-hexanedione. The lipophilicity of the molecule allows distribution to many tissues including the nervous system. Thus, chemical structure and metabolism are important prerequisites for this toxicity. Exposure to the solvent carbon disulphide in industry causes neuronal damage in the central and peripheral nervous system. 

OTHER COMMENTS used as a solvent useful as a laboratory reagent methyl butyl ketone enhances the toxicity of some other chemical substances like carbon tetrachloride, chloroform, and ethanol. 

The metabolites of n-hexane injected in guinea pigs were reported as 2,5- hexane-dione and 5-hydroxy-2-hexanone, which are also metabolites of methyl butyl ketone (DiVincenzo et al. 1976). Thus methyl butyl ketone and n- hexane should have similar toxicities. The neurotoxic metabolite, 2,5-hexanedione, however, is produced considerably less in n-hexane. However, in the case of hexane, the neurotoxic metabolite 2,5-hexanedione is produced to a much lesser extent. Continuous exposure to 250 ppm n-hexane produced neurotoxic effects in... 

The latter compound results from loss of two hydrogen atoms by metabolic oxidation at each of two of the carbon atoms of hexane, and their replacement by oxygen atoms. Schaumburg and Spencer not only demonstrated this, but also showed that the identical neurotoxic events result from direct exposure to compound II and also another common solvent called methyl-n-butyl ketone (III). Chemical III is, like hexane, readily metabolized to the active toxicant, molecule II. Because both I and III yield the same metabolite (II), and because this metabolite is the source of toxicity, then exposure to both of these chemicals produces the identical type of neuropathy. 

Bos PMJ, de Mik G, Bragt PC Critical review of the toxicity of methyl w-butyl ketone risk from occupational exposure. Am 7 MMci 20 175-194, 1991... 

Animal studies have shown MEK to enhance the development of or increase the severity of neurotoxic effects due to methyl n-butyl ketone, ethyl butyl ketone, -hexane, and 2,5-hexanedione."MEK exposure did not, however, potentiate the neurobehavioral test decrements produced by acetone. Exposure to 200 ppm MEK or 100 ppm MEK plus 12 5 ppm acetone for 4 hours did not produce any significant effects in a variety of behavioral performance tests, whereas exposure to 250 ppm acetone caused some mild decrements. The liver and kidney toxicity of haloalkane solvents may also be potentiated by MEK. ... 

Abdel-Rahman MS, Hetland LB, Couri D. 1976. Toxicity and metabolism of methyl n-butyl ketone. Am Ind Hyg Assoc J 37 95-102. 

Makkawy HM, Graham DG, Abou-Donia MB. 1981. Differential neuro toxicity ofn-hexane methyl-n -butyl ketone, 2,5-hexanediol and 2,5-hexanedione following subchronic 90 days oral administration in hens. Fed Proc 40 678. 

Raleigh RL, Spencer PS, Schaumburg HH. 1975. Toxicity of methyl-n-butyl ketone. Arch Environ Health 30 317-318. 

Less commonly used solvents include methyl ethyl ketone, b.p. 80° ethylene chloride, b.p. 84° dioxan (diethylene dioxide), b.p. 101° (vapours are toxic) toluene, b.p. 110° pyridine, b.p. 115-5° chlorobenzene, b.p. 132° cellosolve (ethylene glycol monoethvl ether), b.p. 134-5° di- -butyl ether, b.p. 141° s-tetrachloro-... 

Ethyl acetate is used in production of acrylic plastics. Ethyl acetate and butyl acetate find wide usage as solvents for nitrocellulose and lacquers. Hthyl acetate is considered one of the least toxic of all industrial organic solvents. Buiyl acetate s chief industrial competitor is methyl isobutyJ ketone. Over lime, ethyl acetate and butyl acetate may suffer the same fate as methyl acetate, which hos been largely displaced by other solvents. 

Capello et al.16 applied LCA to 26 organic solvents (acetic acid, acetone, acetonitrile, butanol, butyl acetate, cyclohexane, cyclohexanone, diethyl ether, dioxane, dimethylformamide, ethanol, ethyl acetate, ethyl benzene, formaldehyde, formic acid, heptane, hexane, methyl ethyl ketone, methanol, methyl acetate, pentane, n- and isopropanol, tetrahydrofuran, toluene, and xylene). They applied the EHS Excel Tool36 to identify potential hazards resulting from the application of these substances. It was used to assess these compounds with respect to nine effect categories release potential, fire/explosion, reaction/decomposition, acute toxicity, irritation, chronic toxicity, persistency, air hazard, and water hazard. For each effect category, an index between zero and one was calculated, resulting in an overall score between zero and nine for each chemical. Figure 18.12 shows the life cycle model used by Capello et al.16... 

Nitrocellulose, polyester, acrylic and methacrylic ester copolymer, formaldehyde resin, rosin, cellulose acetate butyrate are the most frequently used polymers in nail polish formulations. Solvents were selected to suit the polymer used. These include acetone, methyl acetate, ethyl acetate, butyl acetate, methyl glycol acetate, methyl ethyl ketone, methyl isobutyl ketone, toluene, xylene, isopropyl alcohol, methyl chloroform, and naphtha. Solvents constitute a substantial Ifaction of the composition usually around 70%. Reformulation is ongoing to improve the flexibility and durability of the nail polish. Other efforts are directed to improve antifungal properties,to eliminate ketones and formaldehyde resin (ketones because of their toxicity and irritating smell and formaldehyde resins because they contribute to dermatitis), and elimination of yellowing. All efforts are di-... 

Nowadays, the most commonly used solvents are mineral or white spirits. Aromatic hydrocarbon solvents, such as xylene and toluene, are used in certain specialized industrial paints. Other solvents include a wide variety of alcohols (isobutanol, i-butanol), esters (ethyl acetate, butyl or isobutylacetate) and ketones (acetone, methyl ethyl ketone). Often, a mixture of different solvents is used to ensure the desired outcome, e.g., in thinners (Mathias 1984 Valsecchi et al. 1992 Rose and Vance 1997 Leira 1997). In Scandinavia, there has been a tendency for more than a decade to reduce the use of the more toxic solvents, including benzene, n-hexane and the chlorinated solvents, particularly carbon tetrachloride, chloroform, dichloroethane and trichloroethylene (Leira 1997). 

In order to reduce the need for strict control and heavy taxation on industrially produced ethanol, the alcohol is denatured. Denaturing is a process of adding other compounds to the ethanol to render it unfit for consumption. Denaturants are selected to give the ethanol a disagreeable taste or odor and in some cases a distinctive color. In some cases the substances added are toxic and produce gastric disturbances upon ingestion and/or other unpleasant symptoms. A large number of different "denaturants" are utilized dependent upon the use for which the ethanol is intended. These denaturants include methyl isobutyl ketone, pyronate, kerosene, acetone, turpentine, amyl alcohol, methyl alcohol, and various butyl alcohols. In some cases more than one denaturant is utilized. 

---