Possible metabolic interaction between hexane and other solvents co-exposed at sub-occupational exposure limit levels

Kawai, Takeshi; Miyama, Y.; Horiguchi, Susumu; Sakamoto, Kazutoshi; Zhang, Z.-W.; Higashikawa, Kae; Ikeda, Masayuki

doi:10.1007/s004200000165

Cited by 12 publications

(11 citation statements)

References 26 publications

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Section: Hydrocarbon Solvent Categoriesmentioning

confidence: 99%

“…There are also studies in which the effects of benzene have been modified by coexposure to other aromatics to either enhance or inhibit the formation of reactive metabolites (Bird et al 2010, Medinsky et al 1994, Tardif et al 1992, Travis et al 1992. However, the effects of co-exposures on metabolism are unlikely except at relatively high exposure levels, associated with experimental conditions at which metabolizing enzymes are saturated (Kwai et al 2000, Ogata et al 1993. Further, as indicated above, aside from some well-characterized exceptions, the constituents of hydrocarbon solvents have similar and relatively subtle toxicological effects.…”

Section: Potential Interactions Among Hydrocarbon Solvent Constituentmentioning

confidence: 99%

“…The most common example is that the aromatic constituents induce their own metabolism, leading to more rapid excretion of hydrocarbons. However, under conditions at which metabolism is not saturated, which is normally the case for the exposure situations under which these substances are used, interactive effects are not expected (Kwai et al 2000, Ogata et al 1993.In summary, hydrocarbon solvents are well suited for category formation, because, for the most part, the constituents with similar physical and chemical properties also have common metabolic and toxicological properties. There are a few constituents with distinctive properties that can be present at toxicologically relevant levels, but these are well characterized and differentiated through the naming convention, as described in Section Nomenclature for hydrocarbon solvents -the naming convention.…”

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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: Hydrocarbon Solvent Categoriesmentioning

confidence: 99%

Section: Potential Interactions Among Hydrocarbon Solvent Constituentmentioning

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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“…The treatment used (with or without acid or enzymatic hydrolysis), coexposure to other solvents, and the time of sampling could all influence the urinary excretion of 2,5-HD (Kawai et al 1990). Moreover, free 2,5-HD has been measured in only a few studies, all of which were carried out in the workplace and involved co-exposure to other solvents (Kawai et al 1990(Kawai et al , 1991b(Kawai et al , 1992a(Kawai et al , 1992b(Kawai et al , 2000Cardona et al 1996).…”

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confidence: 99%

Comparison of unchanged n -hexane in alveolar air and 2,5-hexanedione in urine for the biological monitoring of n -hexane exposure in human volunteers

Hamelin

Truchon

Tardif

2004

International Archives of Occupational and Environmental Health

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Both free urinary 2,5-HD and HEX in alveolar air measurements could be used for the biological monitoring of HEX. Between these two indicators, HEX in alveolar air is less variable than 2,5-HD in urine, but the sampling time is more critical. Therefore, biological monitoring of HEX based on the measurement of free urinary 2,5-HD is preferable to HEX in alveolar air. Additionally, we believe that the 2,5-HD values reported in this study better reflect the actual levels of exposure to HEX alone than what has been previously reported in studies that involved co-exposure to other solvents, and that the current BEI value for HEX is most likely more protective than what has been believed up until now.

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“…It is also known that no metabolic interaction will take place between organic solvents when the exposures are low, e.g., below occupational exposure limits 36,37) . In fact, no metabolic modification was detected among workers exposed to toluene in combination with xylenes [38][39][40] , hexane 41) or ethyl acetate 42) at the concentrations below respective occupational exposure limits. Thus, chances should be very remote for the present study that toluene metabolism was modified by other solvents co-exposed.…”

Section: O Inoue Et Almentioning

confidence: 99%

Limited Validity of o-Cresol and Benzylmercapturic Acid in Urine as Biomarkers of Occupational Exposure to Toluene at Low Levels

et al. 2008

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This study was initiated to evaluate o-cresol and benzylmercapturic acid in urine in comparison with other biomarkers, as tools to estimate the intensity of occupational exposure to toluene at low levels. In total, 108 solvent exposed workers (engaged in tape production) and 17 non-exposed controls (all men) participated in the study. The surveys were conducted in the second half of working weeks. Diffusive sampling was conducted to measure 8-h time-weighted average intensity of occupational exposure to toluene. Blood and urine samples were collected at the end of a working shift. Blood samples were subjected to analysis for toluene (Tol-B), and urine samples were analyzed for benzyl alcohol (BeOH-U), benzylmercapturic acid (BMA-U), ocresol (o-CR-U), hippuric acid (HA-U) and toluene (Tol-U) by the methods previously described. The toluene concentrations in workplaces were low in general, with a geometric mean (GM) and the maximum concentration of 1.9 ppm and 8.8 ppm, respectively. The statistical analyses of the six biomarkers for correlation with air-borne toluene showed that both Tol-B and Tol-U gave a high correlation coefficient of 0.58 to 0.61 (p<0.01), whereas the coefficients for BeOH-U and BMA-U together with HA-U were all low (up to 0.22, depending on the correction for urine density) and statistically insignificant (p>0.10) in most cases. o-CR-U had an intermediary coefficient of 0.20 (p<0.05). Comparison with previous publications disclosed that BeOH-U, BMA-U and HA-U correlate with toluene in air when the exposure is intense (e.g., 50 ppm or above), but no longer proportional to air-borne toluene when the exposure is low, e.g., 2 ppm. Such appeared to be also the case for o-CR-U. In over-all evaluation, the validity of o-CR-U in monitoring occupational exposure to toluene at low levels (e.g., 2 ppm) appear to be limited, and BMA-U is not an appropriate biomarker. BeOH-U and HA-U are also inappropriate for this purpose. Only Tol-B and Tol-U may be employed to estimate toluene exposure at low levels.

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Possible metabolic interaction between hexane and other solvents co-exposed at sub-occupational exposure limit levels

Abstract: When the exposures were below occupational exposure limits, the free-HD levels in urine after HEX exposure will not be modified by co-exposures to TOL, EA or ACE.

Cited by 12 publications

References 26 publications

Characterization of the toxicological hazards of hydrocarbon solvents

Characterization of the toxicological hazards of hydrocarbon solvents

Comparison of unchanged n -hexane in alveolar air and 2,5-hexanedione in urine for the biological monitoring of n -hexane exposure in human volunteers

Limited Validity of o-Cresol and Benzylmercapturic Acid in Urine as Biomarkers of Occupational Exposure to Toluene at Low Levels

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