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Biomedical subjects

G Truchon

Publications and source records attributed to G Truchon.

13 recordsLinked to original sources

Physiologically based modeling of n-hexane kinetics in humans following inhalation exposure at rest and under physical exertion: impact on free 2,5-hexanedione in urine and on n-hexane in alveolar air.

We used a modified physiologically based pharmacokinetic (PBPK) to describe/predict n-hexane (HEX) alveolar air concentrations and free 2,5-HD urinary concentrations in humans exposed to n-HEX by inhalation during a typical workweek. The effect of an increase in workload intensity on these two exposure indicators was assessed and, using Monte Carlo simulation, the impact of biological variability was investigated. The model predicted HEX alveolar air concentrations at rest of 19.0 ppm (25 ppm exposure) and 38.7 ppm (50 ppm exposure) at the end of the last working day (day 5), while free 2,5-HD urinary concentrations of 3.4 micromol/L (25 ppm) and 6.3 micromol/L (50 ppm) were predicted for the same period (last 4.5 hours of Day 5). Monte Carlo simulations showed that the range of values expected to occur in a group of 1000 individuals exposed to 50 ppm of HEX (95% confidence interval) for free 2,5-HD (1.7-14.7 micromol/L) is much higher compared with alveolar air HEX (33.4-46 ppm). Simulations of exposure at 50 ppm with different workloads predicted that an increase in workload intensity would not greatly affect both indicators studied. However, the alveolar air HEX concentration is more sensitive to modifications of workload intensity and time of sampling, after the end of exposure, compared with 2,5-HD. The PBPK model successfully described the HEX alveolar air concentrations and free 2,5-HD urinary concentrations measured in human volunteers and is the first, to our knowledge, to describe the excretion kinetics of free 2,5-HD in humans over a 5-day period.

Exercise↗

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.

INTRODUCTION AND AIM: Biological monitoring of n-hexane (HEX) is based on the measurement of urinary 2,5-hexanedione (2,5-HD). In 2001, the American Conference of Governmental Industrial Hygienists modified the biological exposure index (BEI) for HEX and suggested measuring free urinary 2,5-HD (without hydrolysis) (3.5 micromol/l) instead of total 2,5-HD (acid hydrolysis). This BEI value was derived from four field studies that involved worker exposures to variable concentrations of HEX and other solvents. This study was undertaken to characterize, for 5 consecutive days, the relationship between HEX exposure (25 ppm and 50 ppm) and (1). 2,5-HD urinary excretion and (2). HEX in alveolar air. METHODS: Five volunteers (three women, two men) were exposed to HEX in an exposure chamber for 2 non-consecutive weeks (7 h/day). They were exposed to 50 ppm HEX, during the first week and to 25 ppm during the second week. Alveolar air and urine samples were collected at different intervals before, during and after the exposures. The concentration of unchanged HEX in alveolar air and the concentration of urinary 2,5-HD under three analytical conditions (with acid, or enzymatic hydrolysis and without hydrolysis) were measured. RESULTS: The results show that the mean concentrations of HEX in alveolar air were 18 ppm (25 ppm) and 37 ppm (50 ppm), which indicates that approximately 73% of inspired HEX was expired unchanged in alveolar air by the volunteers. The mean (+/- SD) concentrations of urinary 2,5-HD for the last 4 h of exposure at the end of the week (day 5) following exposure to 50 ppm HEX were 30.4 micromol/l (+/-7.8 micromol/l) (acid hydrolysis); 5.8 micromol/l (+/-1.0 micromol/l) (enzymatic hydrolysis); 6.2 micromol/l (+/-0.9 micro mol/l) (without hydrolysis). Following the volunteers' exposure to 25 ppm HEX, the urinary excretion concentrations were 15.2 micromol/l +/- 1.9 micromol/l, 3.1 micromol/l +/- 0.7 micromol/l and 3.7 micromol/l +/- 0.5 micromol/l, respectively. CONCLUSION: 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.

Adult↗

o-cresol: a good indicator of exposure to low levels of toluene.

This study evaluates the suitability of using urinary excretion of o-cresol (o-CR) as a biological marker of occupational exposure to various concentrations of toluene (TOL). Thirty-eight individuals from three plants involved in the manufacture of paints or inks agreed to participate in the environmental and biological monitoring evaluations, which lasted one to two days. In all, 62 measurements of environmental TOL and urinary o-CR and hippuric acid (HA) levels were made. The eight-hour TOL exposure (time-weighted average [TWA]) ranged from 0 to 111 ppm, depending on plant and job title. TOL exposure was well correlated to post-shift urinary o-CR (r = 0.89) and HA (r = 0.67) levels. At low exposure levels (below 50 ppm), however, o-CR shows a stronger correlation (r = 0.71) than HA (r = 0.24). Based on our results, occupational exposure to 50 ppm of TOL would result in end-of-shift urinary o-CR concentration of 0.72 mumol/mmol creatinine (0.69 mg/L, assuming a urinary creatinine concentration of 1 g/L). This value is of the same order of magnitude as the level proposed by the American Conference of Governmental Industrial Hygienists (ACGIH) in 1998 for exposure to 50 ppm of TOL, namely 0.5 mg/L. Our results suggest that the level of urinary o-CR is a more sensitive index of exposure to low concentrations of TOL than is the urinary concentration of HA.

Chromatography, Gas↗

Gas chromatographic determination of urinary o-cresol for the monitoring of toluene exposure.

A sensitive and reproducible gas chromatographic procedure for the quantitative determination of urinary o-cresol is described. The first step involves acid hydrolysis (2N HCl, 100 degrees C, 10 min), which yields unconjugated o-cresol. After extraction (methylene chloride, pH 2), the organic layer is concentrated by evaporation and samples are analyzed by gas chromatography-flame ionization detection with a DB-5 column (30 m x 0.25 mm, 0.25 microns). Initial oven temperature is set at 30 degrees C for 12 min and the increased 2 degrees C/min to 93 decrees C. 3,4-Dimethylphenol is used as the internal standard. The detection limit of the method is 0.36 mumol/L (1 microL injection). Additional validation data were obtained by analysis of urine samples collected from volunteers exposed to various concentrations of toluene: 10, 20, 30, 50, and 100 ppm over 7 h. Urinary o-cresol concentrations (0-3, 3-7, 7-24, and 0-24 h) were highly correlated with toluene exposure.

Chromatography, Gas↗

Visual dysfunction among styrene-exposed workers.

OBJECTIVES: The present study was undertaken to examine the relation between visual functions and occupational exposure to styrene. METHODS: A total of 128 workers (85% of the total population), from three glass-reinforced plastics plants in Canada, agreed to participate in the study. Environmental and biological measures were made on the day(s) prior to the assessment of near visual acuity (National Optical Visual Chart), chromatic discrimination (Lanthony D-15 desaturated panel), and near contrast sensitivity (Vistech 6000). The analyses were performed on 81 workers with near visual acuity of at least 1 min of arc at 0.5 m. RESULTS: The subjects were relatively young [29 (SD 8) years], with little seniority [5 (SD 4) years]. Styrene exposure for 8 h ranged from 6 to 937 (first quartile 21 mg.m-3, third quartile 303 mg.m-3), depending on the job site. The end-shift concentrations of urinary mandelic acid ranged from nondetectable to 1.90 mmol.mmol creatinine-1. Significant positive relations were found between the internal and external styrene exposure measurements and color vision loss adjusted for age, alcohol consumption, and seniority in a multiple regression analysis. The multiple regression analysis is also showed that the end-shift concentration of urinary mandelic acid was inversely related to contrast sensitivity at 6 and 12 cycles.degree-1. Logistic multiple regression models indicated that the end-shift concentration of urinary mandelic acid was related to the prevalences of blurred vision, tearing, and eye irritation. CONCLUSIONS: These findings suggest that there is a positive relation between styrene exposure and early color and contrast vision dysfunction.

Adult↗

Urinary excretion of mandelic, phenylglyoxylic, and specific mercapturic acids in rats exposed repeatedly by inhalation to various concentrations of styrene vapors.

Adult male Sprague-Dawley rats were exposed by inhalation to various concentrations of styrene vapors (25, 50, 100, or 200 ppm) 6 h/day, 5 days/week, for 4 consecutive weeks. The concentrations were varied from day to day according to a random pattern allowing treated animals to be exposed five times to each concentration of styrene. Each day, the following urinary metabolites were analysed from samples collected during exposure (0-6 h) and after exposure (6-24 h): mandelic acid; phenylglyoxylic acid; and two mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Various parameters of renal toxicity and hepatic microsomal and cytosolic enzyme activities were also measured. The results show that there is a very good relationship between the excretion of all four styrene metabolites and the degree of daily exposure to styrene over the entire period of urine collection, with correlation coefficients ranging from 0.82 to 0.98. The correlation was poor for mandelic acid during the 0-6 h period. There was no evidence that repeated exposure to styrene caused renal toxicity, nor induced hepatic microsomal enzyme activities; cytosolic glutathione S-transferase activity was increased moderately by 1.5 times. Thus, under conditions of exposure to styrene likely to be found in the workplace, all four metabolites measured were good indicators of styrene exposure throughout the length of the experiment. Since mercapturic acids result from the conjugation of styrene oxide with glutathione, the data suggest that measurement of these metabolites offers the possibility to monitor internal exposure to a toxic electrophilic compound more directly.

Acetylcysteine↗

Specific determination of bromobenzene metabolites by high-performance liquid chromatography.

A chromatographic method for the quantitative and simultaneous determination of phenolic and mercapturic acid type metabolites of bromobenzene is presented. Acid hydrolysis (1.5 N HCl, 100 degrees C, 10 min) yielded unconjugated bromophenols. After extraction (ethyl acetate, pH 2), evaporation to dryness and dissolution in methanol, samples were analysed by high-performance liquid chromatography (HPLC) with a c18 reverse-phase column and a phosphate buffer (0.1 M,pH 9 + 5 mM tetrabutylammonium dihydrogen phosphate) - acetonitrile gradient with ultraviolet detection (225 nm). Benzylmercapturic acid and o-chlorophenol were used as internal standards. Using this method, it was possible to determine simultaneously o, m- and p-bromophenols together with o-, m- and p-bromophenylmercapturic acids. Additional validation data were obtained by analysis of urine samples from rats treated with bromobenzene. This new method was compared to existing procedures.

Acetylcysteine↗

Kidney function in male and female rats chronically exposed to potassium dichromate.

Male and female Wistar rats were given 25 mg l-1 chromium (as potassium dichromate) in drinking water for 6 months. Lactate dehydrogenase, lysozyme, total proteins, N-acetyl-beta-D-glucosaminidase, albumin and beta 2-microglobulin (beta 2-m) were measured in 24-h urine after 3 and 6 months of exposure. Body and kidney weight and chromium excretion were also examined. Except for the chromium excretion, no statistically significant changes were observed in the exposed male rats. In female rats there were significant increases in the urinary excretion of albumin after 3 and 6 months of exposure and the urinary excretion of beta 2-m after 3 months of exposure.

Animals↗

Adjustment of permissible exposure values to unusual work schedules.

Research activities sought development of a method to adjust exposure limits for 694 substances for unusual work schedules. A consensus was established on the basic toxicological principle for adjustment; criteria for adjustment were selected by a panel of scientists coordinated by a committee of international experts and supported by toxicokinetic modeling; and a group of toxicologists attributed primary health effects and related adjustment category to each substance. A consensus among scientists and employers' and workers' representatives was established on the protocol of the application, in the field, of the adjusted exposure limits. The guiding toxicological principle for adjusting exposure standards to unusual work schedules is to guarantee an equivalent degree of protection for workers with unusual schedules as for workers with a conventional schedule of 8 hours per day, 5 days per week. The process of the adjustment is inspired from the Occupational Safety and Health Administration logic for attribution of primary health effects and adjustment categories ranging from no adjustment to daily or weekly adjustments. The adjusted exposure limits are calculated according to Haber's rule. Decisions on attribution of adjustment categories for the following toxicological effects were reached: respiratory sensitizers (asthma); skin sensitizers; tissue irritants versus tissue toxicants; methemoglobinenia-causing agents; cholinesterase inhibitors; and reproductive system toxicants and teratogens. A simple procedure is presented to facilitate the calculation, application, and interpretation of the adjusted exposure limits.

Guideline Adherence↗

Simultaneous determination of urinary mandelic, phenylglyoxylic, and mercapturic acids of styrene by high-performance liquid chromatography.

We have developed a relatively simple and reproducible HPLC procedure for the determination of urinary metabolites of styrene. Urine samples (pH 2) are extracted with ethyl acetate, the organic layer is evaporated to dryness, and the residues are dissolved in water-methanol (1:1). Samples are analyzed by HPLC with a C18 reversed-phase column and a water (pH 6, 5mM tetrabutylammonium dihydrogen phosphate)-acetonitrile gradient and ultraviolet detection at 225 nm. Using this method, it is possible to determine simultaneously mandelic and phenylglyoxylic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1), and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). The internal standard is p-hydroxybenzoic acid. Additional validation data are obtained by analysis of urine samples obtained from rats treated with a wide range of styrene doses.

Acetylcysteine↗

Pilot study of peripheral markers of catecholaminergic systems among workers occupationally exposed to toluene.

In a pilot study, serum dopamine beta-hydroxylase (DBH), platelets monoamine oxidase type B (MAO B) activities and basal plasma prolactin (PRL) were measured, among 10 workers occupationally exposed to toluene and 10 control subjects, preceding and immediately following vacation. Six exposed subjects were employed in an adhesive tape making industry and 4 in a paint making industry. Their median basal levels of urinary hippuric acid were 0.44 mmole/mmole creatinine (cr) (range 0.23-1.97) and 0.18 mmole/mmole cr (range 0.15-0.19) respectively, the second to last morning of the work week, preceding vacation. The level of basal urinary hippuric acid among the control group was 0.26 mmole/mmole cr (range 0.03-0.38). The workers from the adhesive tape plant reported a significantly higher number of symptoms experienced frequently (Kruskal, Wallis, p < 0.05). On a group basis, serum DBH was lowest among the workers from the adhesive tape plant, who had the highest levels of basal urinary hippuric acid. In addition, a negative relation was observed between hippuric acid and serum DBH, preceding and following vacation (Rho = -0.46, p = 0.05; Rho = -0.51, p = 0.03). The observed changes in serum DBH activity are consistent with its decrease in human, following long-term exposure to styrene, another aromatic hydrocarbon. The findings of this pilot study, on a limited number of individuals suggest that DBH may be a sensitive peripheral bioindicator. Further studies of larger groups should be done to confirm the decrease in serum DBH activity with toluene exposure and explore whether this alteration is related to the neurotoxic impairments associated with exposure.

Adult↗

Surveillance of early neurotoxic dysfunction.

Surveillance of early neurotoxic alterations was undertaken in 3 reinforced plastics plants, with a view to preventive intervention. Using a longitudinal study design, exposure parameters (environmental styrene in the respiratory zone of each worker and end-shift mandelic acid (MA)) and neurobehavioral performance (Neurobehavioral Core Test Battery and Field Assessment: Sensory Tests), were assessed at time zero (T0); recommendations were made to reduce exposure at jobsites with the highest risk. Reassessment was made two years later (T2). Complete exposure data was available for 118 workers at T0; 75 were still employed at T2; of these, 57 (76%) returned for testing. Those who returned had more seniority (p < 0.001) and higher MA (p < 0.01) and styrene (p < 0.05) levels at T0 than the others. Analyses, performed on the T0-T2 differences, showed improvement in exposure parameters in Plant 3, where lower levels were observed at T2 for styrene (p < 0.05) and MA (p < 0.001). workers in Plant 3 (n = 29) performed better (p < 0.05) at T2 for short term memory, perceptuo-motor speed, motor precision and manual dexterity; they reported more vigor (p < 0.05) and less anger (p = 0.07). This was not the case for the workers from the other plants. Generally, the T0-T2 difference in MA was associated (Spearman's Rho) with differences in color vision (p < 0.001), simple reaction time (mean and standard deviation), digit span forward, tension, fatigue and the number of symptoms (p < 0.05); aiming precision showed a similar tendency (p < 0.10). These findings suggest that group surveillance of early nervous system changes for jobs with exposure to neurotoxins, using a sensitive neurofunctional test battery, may be useful for preventive intervention.

Adult↗