The relative neurotoxicity of methyl-n-butyl ketone, n-hexane and their metabolites

Krasavage, Walter J.; O’Donoghue, John L.; DiVincenzo, G.D.; Terhaar, C. J.

doi:10.1016/0041-008x(80)90338-5

Cited by 209 publications

(66 citation statements)

References 13 publications

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“…Histological examination of the nervous system tissue revealed that n-hexane and its metabolites caused morphological changes indicative of "giant axonal" neuropathy including multifocal axonal swellings, adaxonal myelin in-folding, and paranodal myelin retraction. The authors also reported evidence of testicular atrophy, but a detailed characterization of the testicular effects was outside the scope of the study (Krasavage et al 1980). The study also provided evidence that n-hexane-induced "giant axonal" neuropathy was dependent on the production of a g-diketone metabolite which is unique to n-hexane.…”

Section: Repeated Oral Toxicity Studiesmentioning

confidence: 75%

“…Mid and high doses for n-hexane were 13.2 and 46.2 mmol/kg respectively. Hind limb paralysis observed in order of decreasing potency was 2,5-hexanedione  5-hydroxy-2-hexanone  2,5-hexanediol  2-hexanone  2-hexanol  n-hexane (Krasavage et al 1980). Severity of toxicity correlated with peak serum concentrations of 2,5-hexanedione.…”

Section: Hydrocarbon Solvent Constituents With Unusual Toxicological mentioning

confidence: 87%

“…This neuropathy has been observed in humans and has also been reproduced in animals under experimental conditions (the basis for classification of n-hexane as a specific-organ toxicant) (Frontali et al 1981, Ono et al 1981, Takeuchi et al 1980. There is also evidence that 2,5-hexanedione can interfere with spindle fiber formation, inhibiting meiosis, and resulting in testicular atrophy 17 (Krasavage et al 1980). Other hydrocarbon solvent constituents of similar structure or carbon number including n-pentane, other hexane isomers, n-heptane and cyclohexane are not metabolized to 2,5-hexanedione intermediates and do not cause peripheral neuropathy (Egan et al 1980, Frontali et al 1981, Ono et al 1981, Takeuchi et al 1980.…”

Section: Hydrocarbon Solvent Constituents With Unusual Toxicological mentioning

confidence: 92%

“…As described in the previous paragraph, n-hexane is metabolized to 1-or 2-hexanol, and 2-hexanol is then converted to 2-hexanone (methyl-n-butyl ketone) and 2,5-hexanediol, both of which are converted to 5-hydroxy-2-hexanone and 2,5-hexanedione as principal metabolites (DiVincenzo et al 1977, Krasavage et al 1980. To identify the metabolite responsible for distal axonopathy in response to n-hexane exposure, Krasavage and colleagues gave groups of 5 rats similar doses of all of the n-hexane metabolites that had been identified (Figure 4), that is, 660 mg/kg/day 2-hexanone, 755 mg/kg/day 2,5-hexanedione, 675 mg/kg/day 2-hexanol, 765 mg/kg/day 5-hydroxy-2-hexanone, and 755 mg/kg/day 2,5-hexanediol, as well as 3 doses of commercial n-hexane (570, 1140, and 3980 mg/kg/ day), by oral gavage, for 90 days (Krasavage et al 1980). All doses (including the lowest dose for n-hexane) were equivalent to 6.6 mmol/kg.…”

Section: Hydrocarbon Solvent Constituents With Unusual Toxicological mentioning

confidence: 99%

“…Severity of toxicity correlated with peak serum concentrations of 2,5-hexanedione. Only in rats treated with the high dose of n-hexane, producing serum concentrations close to the peak levels of 2,5-hexanedione, was clear evidence of peripheral nervous system toxicity observed (Krasavage et al 1980). …”

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confidence: 99%

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Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one-and tworing species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/ chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations. Introduction Scope and purpose of the documentThe present document summarizes information on the physical/ chemical properties and toxicological hazards of hydrocarbon solvents and provides examples of the ways in which the information on hazard characterization can be used for hazard classification and to set occupational exposure limits. Many of the toxicological studies were published separately, but the results are summarized herein and referenced in the appendices.Hydrocarbon solvents are liquid hydrocarbon fractions that are primarily produced by the distillation of petroleum feed stocks or their synthetic analogs (e.g., Fischer-Tropsch derived materials), sometimes followed by additional processing steps such as solvent extraction, hydrodesulfurization, or hydrogenation. 1 Most hydrocarbon solvents are complex substances with variable compositions and are best described as UVCB 2 (unknown and variable composition) substances, but some are single constituent (mono-constituent) substances. The complex and variable nature of these solvents is the consequence of their manufacturing processes. In short, most hydroca...

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Section: Repeated Oral Toxicity Studiesmentioning

confidence: 75%

Section: Hydrocarbon Solvent Constituents With Unusual Toxicological mentioning

confidence: 87%

Section: Hydrocarbon Solvent Constituents With Unusual Toxicological mentioning

confidence: 92%

Section: Hydrocarbon Solvent Constituents With Unusual Toxicological mentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Ketones of Six to Thirteen Carbons

O’Donoghue

2023

Patty's Toxicology

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Ketones of carbon number 6–13 are important commercial and industrial materials. Their primary use is as solvents that find use in numerous products and industrial applications. Due to their volatility, environmental regulations have been directed at restricting emissions, particularly to the atmosphere. A number of the ketones discussed in this chapter not only can undergo photochemical transformations that contribute to their abiotic degradation but may also contribute to the formation of smog. Regulations limiting or prohibiting release of materials that may contribute to smog formation are leading to reductions in the use of some of these materials. The ketones covered in this chapter are mainly of concern due to inhalation and dermal exposure routes. Acute exposure to high vapor concentrations of these materials may result in narcosis; however, such exposures are rare except in cases of accidents. Repeated exposure to certain of these ketones may result in peripheral neuropathy or hepatic effects.

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Monohydric Alcohols: C ₁ to C ₆

Bevan

2023

Patty's Toxicology

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This chapter reviews both linear and branched monohydric aliphatic C 1 to C 6 alcohols. The C 7 to C 20 monohydric alcohols are covered in Chapter 74. The low‐molecular‐weight alcohols, including methanol, ethanol, 1‐propanol, and isopropanol, are used extensively in industry. These alcohols exist as volatile liquids at ambient temperatures, and exposure can occur in both industrial and nonindustrial environments. The C 1 to C 6 monohydric alcohols are flammable, but not reactive. The health effects in laboratory animals and in humans for the C 1 to C 6 alcohols are reviewed, as well as workplace exposure methods and biomonitoring and/or biomarker information.

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The relative neurotoxicity of methyl-n-butyl ketone, n-hexane and their metabolites

Cited by 209 publications

References 13 publications

Characterization of the toxicological hazards of hydrocarbon solvents

Characterization of the toxicological hazards of hydrocarbon solvents

Ketones of Six to Thirteen Carbons

Monohydric Alcohols: C ₁ to C ₆

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The relative neurotoxicity of methyl-n-butyl ketone, n-hexane and their metabolites

Cited by 209 publications

References 13 publications

Characterization of the toxicological hazards of hydrocarbon solvents

Characterization of the toxicological hazards of hydrocarbon solvents

Ketones of Six to Thirteen Carbons

Monohydric Alcohols: C 1 to C 6

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Product

Resources

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Monohydric Alcohols: C ₁ to C ₆