Biomedical subjects

J Brodeur

Publications and source records attributed to J Brodeur.

At least 37 records · Page 2Linked to original sources

PubMed1994

Ethanol induced modification of m-xylene toxicokinetics in humans.

This study was undertaken to determine whether previous subacute treatment with ethanol could modify the kinetics of m-xylene in humans. A group of six volunteers was exposed twice to either 100 or 400 ppm of m-xylene during two hours (between 0800 and 1000). Ethanol was given orally in the early evening on each of two consecutive days before exposures (total ethanol intake of 137 g). Such ethanol pretreatment affected the kinetics of m-xylene but only at the high exposure (400 ppm). The modifications were: (1) decreased concentration of m-xylene in blood and alveolar air during and after exposure; (2) increased urinary excretion of m-methylhippuric acid at the end of exposure. Ethanol treatment also enhanced the elimination of antipyrine in saliva. Overall, this study showed that the effect of enzyme induction on the metabolism of m-xylene, after ethanol ingestion, depends on the exposure concentration and is not likely to occur as long as the exposure concentrations remain under the current maximum allowable concentration (100 ppm) in the workplace.

Adult↗

PubMed1994

Toxic interactions among environmental pollutants: corroborating laboratory observations with human experience.

Combined exposures to multiple chemicals may result in interactions leading to a significant increase or decrease in the overall toxicity of the mixture compared to the summation of the toxicity of the components. A large number of chemical interactions have been described in animal studies by administering high doses of chemicals by routes and scenarios often different from anticipated human exposures. Though limited, there is some evidence for the occurrence of several supra-additive (the combined effects are greater than the simple summation of the individual effects) and infra-additive (the combined effects are smaller than the simple summation of the individual effects) chemical interactions in humans. For example, toxicokinetic interactions between several solvents have been found to occur in the workplace, whereas those involving pesticides have been reported less frequently, especially during accidental exposures. Toxic interactions involving nutritionally important metals and metalloids appear to occur more frequently, since several of them have an important role in a variety of physiological and biochemical processes. On the contrary, there is not much evidence to confirm the occurrence of toxic interactions among the commonly encountered inorganic gaseous pollutants in humans. Overall, the majority of chemical interactions observed in animal studies have neither been investigated in humans nor been extrapolated to humans based on appropriate mechanistic considerations. Future research efforts in the chemical interactions arena should address these issues by focusing on the development of mechanistically and biologically based models that allow predictions of the extent of interactions likely to be observed in humans.

Air Pollutants↗

PubMed1994

[Research on factors determining health: role of the environment in the 21st century].

During the next few decades, actions on matters dealing with environmental pollution will have to be aimed at: 1) eliminating environmental contaminants at the source; 2) identifying biomarkers of exposure and/or adverse health effects; 3) improving our skills at assessing the probability of occurrence of adverse health effects in the community; and 4) informing the Canadian public in a responsible manner. Primary sources of pollution related to human activities should be our deep concern: utilization of energy sources, particularly fossil fuels; agricultural activities, such as deforestation and use of fertilizers and pesticides; and industrialization, responsible for the synthesis of numerous new molecules. Clinical investigators will be faced with rare disease entities characterized by low-level, long-term exposure via food, air, water and soil, and low-incidence responses (e.g. cancer, neurotoxicity, reproductive failure, immunotoxicity). Epidemiologists and toxicologists will be pressed, by the Canadian public, to answer questions regarding the probability of occurrence of health effects as a result of exposure to environmental contaminants. Collectively, as scientists, our attitudes will have to change drastically; high in the order of importance is the need to communicate with the public and to diligently inform our fellow citizens about the relationship between health and environment. In doing so, we might find allies to support our claim that health research in Canada deserves much better support.

Canada↗

PubMed1993

Physiologically based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat.

The present study was undertaken to investigate the mechanism of toxicokinetic interaction between toluene (TOL) and m-xylene (XYL) in vivo in the male Sprague-Dawley rat by physiologically based toxicokinetic (PBTK) modeling. First, the metabolic constants (Vmax and Km) were determined for TOL and XYL individually by conducting a series of closed-chamber inhalation exposures of three rats to starting concentrations of 500 to 4000 ppm. The values of Km (TOL, 0.55 mg/liter; XYL, 0.20 mg/liter) and Vmax (TOL, 4.8 mg/hr/kg; XYL, 8.4 mg/hr/kg) were obtained following best visual fit of PBTK model simulations to experimental data. Then using the same experimental set-up, rats were exposed to three different mixtures of both solvents (500 ppm TOL + 1000 ppm XYL; 1000 ppm TOL + 1000 ppm XYL; 1000 ppm TOL + 500 ppm XYL). The data from the time course of chamber solvent concentrations were analyzed with a binary chemical mixture PBTK model that had four mechanistic hypotheses of metabolic interaction (i.e., no interaction, competitive inhibition, noncompetitive inhibition, and uncompetitive inhibition) quantitatively defined in the liver compartment. The validity of the various model descriptions was verified with open-chamber inhalation exposure data on toxicokinetics of TOL and XYL. Overall, the results of this combined experimental and modeling approach are consistent with a competitive metabolic inhibition between XYL and TOL in the rat.

Animals↗

PubMed1993

A descriptive and mechanistic study of the interaction between toluene and xylene in humans.

This study was undertaken to characterize the mechanism of toxicokinetic interaction between toluene (TOL) and m-xylene (XYL) in the rat using physiologically-based toxicokinetic (PBTK) modeling approach. First, the metabolic rate constants were determined by conducting closed-chamber inhalation exposures with individual solvents (Vmax: TOL = 4.8, XYL = 8.4 mg/hr/kg; Km: TOL = 0.55, XYL = 0.2 mg/l). Then, using the same experimental set-up, rats were exposed to different binary mixtures of TOL and XYL. PBTK analysis of the data showed competitive inhibition as the plausible mechanism of TOL/XYL interaction. This mechanistic modeling study suggests that the interaction between TOL and XYL is likely to be observed when the exposure concentration exceeds 50 ppm of each solvent.

Animals↗

PubMed1993

Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air. I. Toluene and m-xylene.

The present study was undertaken to investigate the influence of different exposure scenarios on the elimination of toluene and m-xylene in alveolar air and other biological fluids in human volunteers. The study was also aimed at establishing the effectiveness of physiologically based toxicokinetic models in predicting the value of biological monitoring data after exposure to toluene and m-xylene. Two adult male and two adult female white volunteers were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of toluene (21-66 ppm) or m-xylene (25-50 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on respective biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of hippuric acid and m-methyl-hippuric acid were determined. The results show that doubling the exposure concentration for both solvents led to a proportional increase in the concentrations of unchanged solvents in alveolar air and blood at the end of a 7-h exposure period. Cumulative urinary excretion of the respective metabolites exhibited a nearly proportional increase. Adjustment of exposure concentration to account for a prolongation of the duration of exposure resulted in essentially identical cumulative urinary excretion of the metabolites. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar concentration for both solvents, depending on whether or not sampling preceded or followed peak exposure to solvent. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of both solvents were increased by 40%. Experimental data collected during the present study were adequately simulated by physiologically based toxicokinetic modeling. These results suggest that alveolar air solvent concentration is a reliable index of exposure to both toluene and m-xylene under various experimental exposure scenarios. For clinical situations likely to be encountered in the workplace, physiologically based toxicokinetic modeling appears to be a useful tool both for developing strategies of biological monitoring of exposure to volatile organic solvents and for predicting alveolar air concentrations under a given set of exposure conditions.

Adult↗

PubMed1992

Modulation of hexachlorobenzene-induced hepatic porphyria by methyl isobutyl ketone in the rat.

Potential toxic interaction between hexachlorobenzene (HCB) and methyl isobutyl ketone (MiBK) was investigated using two different schedules of toxicant administration. The first schedule involved simultaneous administration of HCB (50 mg/kg/d, p.o. in 10 ml/kg corn oil at 10.00 a.m. for 5 d/wk) and MiBK (7.5 mmol/kg/d, p.o. in 10 ml/kg corn oil at 4.00 p.m. for 3 d/wk) for 6 weeks. The second schedule involved an initial dosing of 25 or 50 mg HCB/kg/d for 12 consecutive days, followed by the administration of 7.5 mmol MiBK/kg every other day for 27 days. When administered simultaneously, MiBK reduced the severity of HCB-induced porphyria, but when given sequentially after HCB accumulation, it enhanced the porphyrinogenic response. These results suggest that the effect of combined exposure to HCB and MiBK on hepatic porphyria depends on the sequence of the administration of both chemicals, and that the mechanism involved in this interaction may invoke both the induction and inhibition of specific hepatic isoenzymes by MiBK.

Administration, Oral↗

PubMed1992

Influence of various mixtures of inhaled toluene and xylene on the biological monitoring of exposure to these solvents in rats.

The present study was undertaken to describe the influence of simultaneous exposure by inhalation to toluene and xylene on some aspects of their respective metabolic disposition. Adult male rats were exposed acutely (5 h) to 75, 150, and 225 ppm of toluene or xylene and to various mixtures of these solvents: toluene (75 ppm) and xylene (225 ppm), toluene (150 ppm) and xylene (150 ppm), toluene (225 ppm) and xylene (75 ppm). Compared with single exposure, simultaneous exposure resulted in lower amounts of excreted hippuric acid (20-30%) and methylhippuric acids (4-40%) in urine over a period of 24 h, even though significant differences were seen only with the toluene (150 ppm) and xylene (150 ppm) combination. In addition, increased concentrations of solvents in blood (toluene, 230%; xylene, 500%) and in brain (toluene, 230%; xylene, 320%) were found during the immediate post-exposure period. Simultaneous exposure also enhanced the pulmonary elimination of both solvents (toluene, 190-240%; xylene, 340-650%). Influence of repeated simultaneous exposure (9 days) was investigated for the toluene (150 ppm) and xylene (150 ppm) combination and the results compared with those of repeated exposure to each solvent administered singly. Under these conditions, repeated simultaneous exposure decreased the excretion of urinary metabolites, but only after the first exposure. On the other hand, simultaneous exposure resulted in significantly higher concentrations of toluene (210%) and xylene (240%) in blood throughout the entire 9-day exposure period. These results strongly suggest mutual metabolic interactions (inhibition) between toluene and xylene that affect the metabolic disposition of both solvents and ultimately the biological monitoring of data of exposure to a combination of solvents in rats.

Administration, Inhalation↗

PubMed1991

Male rat specific nephrotoxicity resulting from subchronic administration of hexachlorobenzene.

Male rats are more sensitive to the nephrocarcinogenic effect of hexachlorobenzene (HCB) than are female rats. The purpose of this study was to shed light on this phenomenon by investigating mechanisms of subchronic nephrotoxicity of HCB. Groups of rats were administered HCB in corn oil (po) at 100 mg/kg, 5 days per week for 15 days or at 50 mg/kg, 5 days per week for 50 days. Urine was collected on Days 1, 8, and 15 for the 15-day treatment and on Day 50 for the 50-day treatment. Glucosuria, proteinuria, and enzymuria (gamma-glutamyl transpeptidase) were measured to assess renal function. Twenty-four hours after the last HCB treatment, the animals were killed and kidneys were removed for histopathological evaluation. Urine analyses showed no indication of renal dysfunction in treated animals compared to controls during the 15-day treatment. However, histology of male rat kidneys revealed degenerative and regenerative cellular foci accompanied by an increased accumulation of protein droplets in epithelial cells of the proximal tubules. The same histological observations were also made in male rats after a 50-day HCB treatment but this time they were accompanied by renal function alterations. In female rats, no such renal functional or histological alterations were observed. The histopathological observations in male rats correspond well with the protein droplet nephropathy; the latter is characteristic of the accumulation in kidney cells of alpha 2u-globulin probably caused by the reversible binding of a chemical to alpha 2u that renders the protein indigestible to kidney proteases. alpha 2u-Globulin was measured in the cytosol of male rats and was found to be increased 11-fold compared to controls. Also, HCB was found to be bound reversibly to alpha 2u. These results suggest that HCB induces a male rat specific nephropathy that could explain the higher incidence of kidney tumors in male rats compared to female rats.

Alpha-Globulins↗

PubMed1991

Effect of simultaneous exposure to toluene and xylene on their respective biological exposure indices in humans.

Studies that specifically address the influence of controlled human exposure to a combination of solvents on the biological monitoring of exposure are limited in number. The present study was undertaken to investigate whether simultaneous exposure of human volunteers to toluene and xylene could modify the respective metabolic disposition of these solvents. Five adult Caucasian men were exposed for 7 consecutive h/day over 3 consecutive days to 50 ppm toluene and 40 ppm xylene either separately or in combination in a dynamic, controlled exposure chamber (low-level exposure). The experiment was repeated three times at intervals of 2 weeks. In another experiment, three subjects were exposed to 95 ppm toluene and 80 ppm xylene or a combination of both for 4 h (high-level exposure). The concentration of unchanged solvents in blood (B) and in end-exhaled air (EA) as well as the urinary excretion of hippuric acid (HA) and methylhippuric acids (MHAs) were determined. Simultaneous exposure to the lowest level of solvents did not alter the concentration of unchanged solvents in blood or in exhaled air (average of 3-weekly means; single vs mixed exposure at 6.5 h exposure): B-toluene, 77.1 vs 78.1 micrograms/100 ml; B-xylene, 67.6 vs 77.8 micrograms/100 ml; EA-toluene, 9.9 vs 9.5 ppm; EA-xylene, 5.3 vs 4.8 ppm. Similarly, mixed exposure did not modify the excretion of urinary metabolites during the 3- to 7-h exposure period: HA, 1.11 vs 1.11 g/g creatinine: MHAs, 0.9 vs 0.87 g/g creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Development of an experimental model for the study of hexachlorobenzene-induced hepatic porphyria in the rat.

Hexachlorobenzene (HCB) induces hepatic porphyria in rats. Various protocols of repeated cumulative and daily doses of HCB administered for several weeks until porphyria develops have been traditionally used. In order to undertake studies on early biochemical events occurring in HCB-induced porphyria, we have designed an experimental model involving the administration of a minimal amount of HCB inducing a fully developed porphyria in a well defined and predictable time frame. Groups of Sprague-Dawley rats were given (po, in 10 ml/kg of corn oil) a cumulative dose of 1,500 mg HCB/kg as 50 mg/kg for 6 weeks (5 days/week) or 100 mg/kg for 3 weeks (5 days/week). In female, but not male, rats treated for 6 weeks, HCB caused a porphyria as measured by urinary uroporphyrin and hepatic porphyrin levels; this total dose given to female rats in 3 weeks was not, however, porphyrinogenic. Female rats were given 12 consecutive daily doses of 50 mg HCB/kg followed by a no-treatment period of 30 days; this cumulative dose of 600 mg HCB/kg induced a porphyria after 6 weeks. The approximate minimally effective cumulative dose inducing porphyria was determined to be 400 mg HCB/kg, regardless of the magnitude of the daily dose (25, 50, or 100 mg/kg). Finally, the administration of a cumulative dose of 500 mg HCB/kg (50 mg/kg, 5 days/week for 2 weeks or 100 mg/kg/day for 5 days) induced after 5 to 6 weeks a porphyria that persisted for more than 500 to 600 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Influence of acetone on the severity of the liver injury induced by haloalkane mixtures.

Acetone potentiation of haloalkane-induced liver injury is a well-known phenomenon. Acetone-treated rats challenged with a trichloroethylene-CCl4 mixture exhibit a more sever liver injury than that predicted by the addition of the single potentiating effects of each. The purpose of the present study was to determine if acetone exerted similar interactions with other haloalkane mixtures. The testing protocol used was designed and performed to allow categorization of interactions occurring among two or three agents. Rats were treated (p.o.) with corn oil or acetone (10.2 mmol/kg) and were administered (i.p.) 18 h later 1,1-dichloroethylene (0.6 mmol/kg), trichloroethylene (5.6 mmol/kg), tetrachloroethylene (19.6 mmol/kg), 1,1,1-trichloroethane (10.0 mmol/kg), 1,1,2-trichloroethane (1.1 mmol/kg), 1,1,2,2-tetrachloroethane (1.0 mmol/kg), CHCl3 (6.2 mmol/kg), CCl4 (1.0 mmol/kg), or a mixture of two haloalkanes (all 28 combinations were tested). Liver injury was assessed 24 h later using plasma alanine aminotransferase activity and a quantitative histological evaluation. In corn oil pretreated rats, the hepatotoxic responses observed for the 28 mixtures were additive for 26 of 28 mixtures and supra-additive for 2 of 28, whereas in acetone-pretreated rats the responses observed were additive for 17 of 28, infra-additive for 10 of 28, and supra-additive for 1 of 28. Mixtures containing 1,1,1-trichloroethane or tetrachloroethylene resulted only in no change in toxicity or infra-additivity. Increased toxic responses (additivity and supra-additivity) were observed with certain binary mixtures containing CCl4, CHCl3, 1,1,2-trichloroethane, or 1,1-dichloroethylene.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1989

Influence of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid, on the urinary elimination of mercapturic acids of ethylene oxide, dibromoethane, and acrylonitrile: a dose-effect study.

Metabolic disposition of ethylene oxide, dibromoethane, and acrylonitrile in rats after acute exposure was studied by examining the relationship between dose and urinary metabolites, and by establishing the influence of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the above relationship. Respective urinary metabolites, hydroxyethylmercapturic acid, cyanoethylmercapturic acid, thiocyanate, and ethylene glycol, were quantified to estimate the extent to which each compound was metabolized. The animals were given either ethylene oxide (0.34, 0.68, or 1.36 mmol/kg), dibromoethane (0.2, 0.4, or 0.6 mmol/kg), or acrylonitrile (0.10, 0.38, or 0.76 mmol/kg). Urine samples were collected at 24 h. The metabolic biotransformation of all three chemicals to their respective mercapturic acids was strongly indicative of saturable metabolism. Administration of OCTA (4-5 mmol/kg) enhanced gluthathione availability and increased excretion of urinary mercapturic acids at the higher doses of the chemicals. This study indicates that OTCA increases the capacity for detoxification via the glutathione pathway thereby partially correcting the nonlinearity between the administered dose of ethylene oxide, dibromoethane, and acrylonitrile and the amount of certain urinary metabolites.

Acetylcysteine↗

PubMed1988

Potentiation of CCl4-induced liver injury by ketonic and ketogenic compounds: role of the CCl4 dose.

Potentiation of haloalkane hepatotoxicity by ketones and ketogenic agents is a well-known phenomenon. The importance of the CCl4 dosage in these combinations, however, has not been explored. Its influence was investigated in male Sprague-Dawley rats. Dose-effect curves for potentiation were generated using 1,3-butanediol, methyl n-butyl ketone or methyl isobutyl ketone as potentiation agents. Animals were orally treated with these compounds prior to a challenge of CCl4 (0 to 0.5 ml/kg, ip). Liver injury was assessed by monitoring plasma ALT activity and bilirubin concentrations after CCl4 treatment. The minimal effective dosage (MED) for each potentiator was used as the criterion of comparison for each combination. The MED values were determined from the plasma ALT data. Results showed that when the CCl4 dosage was increased from 0.01 to 0.10 ml/kg, the MED of each potentiator decreased 10-fold. For a given potentiator, the product of the CCl4 dosage (H, "hepatotoxicant") by the corresponding MED value (P, "potentiator") remained the same in this range of CCL4 dosages. The severity of the liver injury was similar. These findings suggest that a given level of liver injury induced by a ketone/haloalkane combination could be evaluated on the basis of the [P X H] product.

Animals↗

PubMed1988

Assessment of the minimal effective dose of acetone for potentiation of the hepatotoxicity induced by trichloroethylene-carbon tetrachloride mixtures.

Administration of acetone to rats in amounts larger than or equal to a minimal effective dosage (MED) is known to potentiate the severity of the liver damage produced by CCl4 alone. It has been reported that CCl4-induced hepatotoxicity is also enhanced by the previous administration of trichloroethylene (TCE). In addition, TCE-CCl4 mixture-induced liver injury is potentiated by acetone. The present study was undertaken to determine if the acetone MED is decreased when the haloalkane challenge is a mixture of TCE-CCl4 instead of CCl4 alone. The effect of varying mixture compositions was also evaluated. In a first series of experiments, male Sprague-Dawley rats received corn oil or acetone (0.05-0.25 ml/kg, po); 18 hr later, they received an ip injection of either CCl4 (0.1 ml/kg) or [TCE (0.25 ml/kg)-CCl4 (0.1 ml/kg)]. In a second series, rats received corn oil or acetone (0.75 ml/kg), and were challenged with TCE (1.5 ml/kg), CCl4 (0.25 ml/kg), or a mixture of TCE-CCl4, where TCE and CCl4 dosages were equal to 25-75%, 50-50%, and 75-25%, respectively, of those used for the administration of the solvents alone. In both series, rats were killed 24 hr after the haloalkane challenge. Liver injury was assessed biochemically (plasma ALT activities and bilirubin concentrations) and morphologically. When TCE was added to a solution of CCl4, smaller doses of CCl4 were required to produce equally severe liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗

PubMed1988

Determination of specific urinary thioethers derived from acrylonitrile and ethylene oxide.

A simple analytical method has been developed for the determination of specific urinary thioethers. Mercapturic acids present in urine are first de-acetylated enzymatically or by acid hydrolysis. Cysteine conjugates thus formed are reacted with o-phthalaldehyde and mercaptoethanol, yielding fluorescent derivatives, which are further separated by high-performance liquid chromatography (HPLC) in a reverse-phase system. The method is applicable to the determination of the following thioethers: 2-hydroxyethylmercapturic acid (N-acetyl-S-2-hydroxyethyl-L-cysteine; HMA), carboxymethylmercapturic acid (N-acetyl-S-carboxymethyl-L-cysteine; CAMA) and 2-cyanoethylmercapturic acid (N-acetyl-S-2-cyanoethyl-L-cysteine; CYMA), and the corresponding cysteine conjugates, S-2-hydroxyethyl-L-cysteine (HCYS), S-2-carboxymethyl-L-cysteine (CACYS) and S-2-cyanoethyl-L-cysteine (CYCYS). The excretion pattern of these thioethers in rats exposed to acrylonitrile and various rodents exposed to ethylene oxide is reported. Thioether excretion can be dependent on species and route of administration. The analytical procedure may prove to be applicable to the biological monitoring in humans of exposure to acrylonitrile, ethylene oxide, vinyl chloride, 1,2-dibromoethane and 1,2-dichloroethane.

Acetylcysteine↗