Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene

Ikeda, Masayuki; Ukai, Hirohiko; Kawai, Toshio; Ito, Osamu; Maejima, Yuki; Fukui, Yoshinari; Ohashi, Fumiko; Okamoto, Susumu; Takada, Shiro

doi:10.1016/j.toxlet.2008.07.011

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…At low concentrations (when Tol-A ≤ 20 ppm), oCre appear to be limited (R² = 0.50). Previous reports have already made this observation for oCre and BMA (Ikeda et al, 2008. In this study, correlation coefficients obtained with MAs decrease at low TOL concentrations (mean R² equal 0.84 instead of 0.96) but they remain high.…”

Section: Discussionsupporting

confidence: 66%

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Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid ando-cresol and blood toluene)

et al. 2013

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1. Toluene (TOL) is a neurotoxic, ototoxic and reprotoxic solvent which is metabolized via the glutathione pathway, producing benzylmercapturic, o-, m- and p-toluylmercapturic acids (MAs). These metabolites could be useful as biomarkers of TOL exposure. 2. The aims of this study were (1) to provide data on MAs excretion in rat urine following TOL exposure by inhalation, (2) to compare them to data from traditional TOL biomarkers, i.e. TOL in blood (Tol-B), and urinary hippuric acid (HA) and o-cresol (oCre) and (3) to establish a relationship between these different indicators and the airborne TOL concentration (Tol-A). 3. Sprague-Dawley rats were exposed to a range of TOL concentrations. Blood and urine were collected and analyzed to determine biomarker levels. 4. Levels of the four MAs correlate strongly with Tol-A (comparable to the correlation with Tol-B). 5. MAs are thus clearly superior to oCre and HA as potential markers of exposure to TOL.

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Section: Discussionsupporting

confidence: 66%

“…BMA has been compared with other markers, and seems to be a better indicator than HA or oCre (Inoue et al, 2002, Inoue et al, 2004. However, at low concentrations (< 15 ppm) it does not correlate as well as Tol-U with Tol-A (Ikeda et al, 2008, Lovreglio et al, 2010.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid ando-cresol and blood toluene)

et al. 2013

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“…All of the potential urinary biomarkers of TOL (hippuric acid (HA), o,m,p-cresols, BMA and o,m,p-toluylmercapturic acids) and MEK (2-butanol, 3-hydroxy-2-butanone and 23BDs) were investigated for this study. Based on previous results, some were already known to be poor biomarkers due to their low specificity or high endogenous excretion (for example hippuric acid, m,p-cresols or 2-butanol) (Ikeda et al, 2008, Cosnier et al, 2013, Cosnier et al, 2017. In a co-exposure context, HA also failed to highlight interaction between TOL and MEK at exposure levels below the 8h-OEL (Ukai et al, 1994, Uaki et al, 1995.…”

Section: Discussionmentioning

confidence: 98%

Toluene and methylethylketone: effect of combined exposure on their metabolism in rat

et al. 2017

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1. Multiple exposures are ubiquitous in industrial environments. In this article, we highlight the risks faced by workers and complete the data available on the metabolic impact of a common mixture: toluene (TOL) and methylethylketone (MEK). 2. Rats were exposed by inhalation under controlled conditions either to each solvent individually, or to mixtures of the two. How the interaction between the two solvents affected their fate in the blood and brain, their main relevant urinary metabolites (o-cresol, benzylmercapturic acid for TOL and 2,3-butanediols for MEK) and their hepatic metabolism were investigated. 3. Although the cytochrome P450 concentration was unchanged, and the activities of CYP1A2 and CYP2E1 isoforms were not additively or synergistically induced by co-exposure, TOL metabolism was inhibited by the presence of MEK (and vice versa). Depending on the relative proportions of each compound in the mixture, this sometimes resulted in a large increase in blood and brain concentrations. Apart from extreme cases (unbalanced mixtures), the amount of o-cresol and benzylmercapturic acid (and to a lesser extent 2,3-butanediols) excreted were proportional to the blood solvent concentrations. 4. In a co-exposure context, ortho-cresol and benzylmercapturic acid can be used as urinary biomarkers in biomonitoring for employees to relatively accurately assess TOL exposure.

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“…Urinary hippuic acid is the most common biomarker for monitoring toluene exposure. It is valid when the toluene exposure level is high (>50 ppm); however, the marker correlates poorly with exposure when the level of toluene exposure is less than 10 ppm (Ikeda et al, 2008;Ukai et al, 2007). In addition, alcohol and cigarette smoking interact with toluene metabolism and have both stimulatory (chronic consumption) and inhibitory (acute consumption) effects on the metabolism of toluene (Inoue et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Subclinical abnormalities in workers with continuous low-level toluene exposure

Shih

et al. 2011

Toxicol Ind Health

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Short-term exposure to a high concentration (TWA > 100 ppm) of toluene can cause hepatotocixity and neurotoxicity in humans. Data on the effects of exposure to low levels of toluene, however, are controversial. In addition, few studies on the effects of toluene exposure on the autonomic nervous system have been conducted. Urine samples from 34 male factory workers in Taiwan who were exposed to low levels of toluene either intermittently (n = 13) or continuously (n = 21) were taken on a Monday morning after a 2-day hiatus and at the end of the workweek on Friday evening. Urinary hippuric acid levels were measured using high-performance liquid chromatography (HPLC). A complete blood work-up was also performed for each subject. The prevalence and severity of neurotoxic symptoms were investigated by a self-reported questionnaire, a neuropsychiatric battery, and sympathetic and peripheral nerve function tests. The mean value of urinary hippuric acid corrected for creatinine (Cr) was 0.34 ± 0.18 g/g Cr on Monday morning and 0.43 ± 0.26 g/g Cr on Friday evening. The difference in the mean value of urinary hippuric acid between the two periods (p < 0.01) and the odds ratio of impairment of sympathetic (OR = 4.13, p = 0.11) and peripheral nerves (OR = 6.94, p = 0.074) were higher in workers continuously exposed to toluene. In addition, workers who were continuously exposed to toluene had a lower mean platelet count (216 ± 41 × 10(6) /µL) than workers who were intermittently exposed (252 ± 40 × 10(6)/µL), (p = 0.018). Furthermore, there was a positive relationship between neurological abnormalities and a self-reported neuropsychiatric measurement (r = 0.35-0.66, p < 0.05) in all workers. These data suggest that continuous exposure to low levels of toluene may be associated with sympathetic and peripheral nerve dysfunction and sub-clinical hematological damage. Further research needs to be carried out regarding how chronic exposure to low-levels of toluene affects workers.

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Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene

Cited by 4 publications

References 37 publications

Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid ando-cresol and blood toluene)

Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid ando-cresol and blood toluene)

Toluene and methylethylketone: effect of combined exposure on their metabolism in rat

Subclinical abnormalities in workers with continuous low-level toluene exposure

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