A control banding method for chemical risk assessment in occupational settings in France.

Background: This study describes a method whose aim is to help companies assess the chemical occupational risks related to labeled products and industrial chemical emissions. The method is intended to be used by industrial hygienists at the scale of one company. Both inhalation and cutaneous exposure routes are taken into account. Methods: The method relies on a control-banding scheme. A work situation is described by exposure parameters such as the process or the local exhaust ventilation and by the hazard of the product. Each possible value of the parameters is associated with a "band," which is associated with an integer value. The multiplication of these values results in a score, which represents a priority for intervention. The higher the score, the more the situation warrants investigation for implementing prevention measures, such as chemical substitution and the addition of local exhaust ventilation. To simplify communication, the priority is associated with a colored priority band: red for "very high priority," orange for "high priority," and green for "moderate priority." The priority bands are computed for all work situations performed in a company. Results: An example of the use of this method is described in a French façade insulation company. Conclusion: A tool named Seirich was developed to implement this method and promote good practices for helping industrial hygienists in the prioritization of interventions for reducing chemical risk in France.

Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030.

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.

A Case Study about Joining Databases for the Assessment of Exposures to Noise and Ototoxic Substances in Occupational Settings.

Evaluating risks associated with multiple occupational exposures is no easy task, especially when chemical and physical nuisances are combined. In most countries, public institutions have created databases, which gather extensive information on occupational exposures or work-related diseases. Unfortunately, these tools rarely integrate medical and exposure information, and, above all, do not take into account the possible adverse effects of co-exposures. Therefore, an attempt to exploit and join different existing databases for the assessment of the health effects of multiple exposures is described herein. This case study examines three French databases describing exposures to noise and/or ototoxic chemicals (i.e., toxic to the ear) and the incidence rate of occupational deafness in different sectors. The goals were (1) to highlight occupational sectors where the workers are the most (co)exposed and (2) to determine whether this approach could confirm the experimental data showing that this co-exposure increases the risk of developing hearing loss. The results present data per occupational sector exposing workers to noise only, ototoxic chemicals only, noise and ototoxic chemicals, and neither of these two nuisances. The ten sectors in which the proportion of exposed workers is the highest are listed. This analysis shows that the rate of hearing loss in these sectors is high but does not show an increased incidence of hearing loss in co-exposed sectors.

The design of a matrix linking work situations to chemical health risk at the workplace.

In France, laws require each company to draw up an inventory of the risks that may threaten employees' health in order to prioritize the preventive actions to be implemented. Focusing on chemical risk, databases on hazards or exposures are widely available but they lack information regarding chemical risks resulting from combining the hazards of chemicals with their conditions of use, thus generating exposures. Our objective is to build a matrix of French work situations associated with their chemical risk. Eighty-eight work situations were collected from reports written by professionals from the French public health insurance service. Each work situation is defined by descriptive parameters of the task, the exposure, and the hazard. According to an expert elicitation method (Delphi, n = 21 experts), each work situation was assessed and a chemical risk score defined, taking into account all the descriptive exposure and hazard parameters. Chemical risk scores were expressed as a range of values from 0 to 100, with the size of the range chosen by the experts themselves according to their uncertainty. The experts' assessments were merged to assign one risk score for each work situation, variability, and confidence. The results showed that 50% of the work situations had a risk score between 40 and 60. The average variability and confidence were around 15% and 82%, respectively. This work situation matrix constructed from French data can be used by occupational safety and health managers that have similar work situations in their company (Western European industrial sector). In this context, it may be useful to easily determine the level of risks for similar tasks and prioritize those that are most risky. Moreover, it could be used to compare and define the differences between a risk assessment performed by "expertise" and another defined by a software.

One-year follow-up of microbial diversity in bioaerosols emitted in a waste sorting plant in France.

Bioaerosols emitted in waste sorting plants (WSP) can induce some adverse health effects on the workers such as rhinitis, asthma and hypersensitivity pneumonitis. The composition of these bioaerosols is scarcely known and most of the time assessed using culture-dependent methods. Due to the well-known limitations of cultural methods, these biodiversity measurements underestimate the actual microbial taxon richness. The aim of the study was to assess the airborne microbial biodiversity by using a sequencing method in a French waste sorting plant (WSP) for one year and to investigate the main factors of variability of this biodiversity. Static sampling was performed in five areas in the plant and compared to an indoor reference (IR), using closed-face cassettes (10 L.min-1) with polycarbonate membranes, every month for one year. Environmental data was measured (temperature, relative humidity). After DNA extraction, microbial biodiversity was assessed by means of sequencing. Bacterial genera Staphylococcus, Streptococcus, Prevotella, Lactococcus, Lactobacillus, Pseudomonas and fungal genera Wallemia, Cladosporium, Debaryomyces, Penicillium, Alternaria were the most predominant airborne microorganisms. Microbial biodiversity was different in the plant compared to the IR and seemed to be influenced by the season.

AltrexChimie, a Web Application for the Management and the Interpretation of Occupational Exposure Measurements to Chemical Substances.

In most occupational settings, several chemical agents are commonly found, and the associated exposure risk for workers must be assessed. For this purpose, air samples can be collected and analyzed. AltrexChimie is a web application that helps industrial hygienists in the organization of the air sampling strategy and in the subsequent phases of data management, analysis, and communication. AltrexChimie contains a database of more than 550 chemical substances and their respective French Occupational Exposure Limit Values (OELV): Custom OELVs can also be defined by the user. AltrexChimie helps with the definition of key features of the sampling strategy, in particular by promoting a methodology for the design of Similar Exposure Groups (SEGs). Once measurement data are entered, they can be analyzed to obtain exposure diagnostics. Data management features allow for the easy storage and retrieval of measurements, and comprehensive dashboards help industrial hygienists (IHs) in the communication of results. Finally, with AltrexChimie it is also possible to assess exposure to multiple chemical substances and their additive effects. While most free software applications for the assessment of chemical exposure focus on the statistical computation of specific indicators, AltrexChimie offers several tools to assist IHs in the exposure assessment workflow. AltrexChimie is available without registration from INRS at https://altrex.inrs.fr.

Expostats: A Bayesian Toolkit to Aid the Interpretation of Occupational Exposure Measurements.

INTRODUCTION: Interpretation of exposure measurements has evolved into a framework based on the lognormal distribution. Most available practical tools are based on traditional frequentist statistical procedures that do not satisfactorily account for censored data and are not amenable to simple probabilistic risk statements. Bayesian methods offer promising solutions to these challenges. Such methods have been proposed in the literature but are not widely and freely available to practitioners. METHODS: A set of computer applications were developed aimed at answering typical inferential questions that are important to occupational health practitioners: Is a group of workers compliant with an occupational exposure limit? Are some individuals within this group likely to experience substantially higher exposure than its average member? How does an intervention influence the distribution of exposures? These questions were addressed using Bayesian models, simultaneously accounting for left, right, and interval-censored data with multiple censoring points. The models are estimated using the JAGS Gibbs sampler called through the R statistical package. RESULTS: The Expostats toolkit is freely available from www.expostats.ca as four tools accessible through a Web application, an offline standalone application or algorithms. The tools include a variety of calculations and graphical outputs useful according to current practices in analysis and interpretation of exposure measurements collected by occupational hygienists. Tool1 and its simplified version Tool1 Express focus on inferences from data from a similarly exposed group. Tool2 evaluates within- and between-worker components of variability, as well as the probability that an individual worker might be overexposed. Tool3 compares exposure data across groups, e.g. evaluates the effect of an intervention. Uncertainty management includes the calculation of credible intervals and produces probabilistic statements about the exposure metrics (e.g. probability that over 5% of exposures are above a limit). DISCUSSION: Expostats is the first freely available toolkit that leverages the flexibility of Bayesian analysis to perform an extensive list of calculations recommended in several international guidelines on the practice of occupational hygiene.

Assessment of occupational exposure to asbestos fibers: Contribution of analytical transmission electron microscopy analysis and comparison with phase-contrast microscopy.

From November 2009 to October 2010, the French general directorate for labor organized a large field-study using analytical transmission electron microscopy (ATEM) to characterize occupational exposure to asbestos fibers during work on asbestos containing materials (ACM). The primary objective of this study was to establish a method and to validate the feasibility of using ATEM for the analysis of airborne asbestos of individual filters sampled in various occupational environments. For each sampling event, ATEM data were compared to those obtained by phase-contrast optical microscopy (PCOM), the WHO-recommended reference technique. A total of 265 results were obtained from 29 construction sites where workers were in contact with ACM. Data were sorted depending on the combination of the ACM type and the removal technique. For each "ACM-removal technique" combination, ATEM data were used to compute statistical indicators on short, fine and WHO asbestos fibers. Moreover, exposure was assessed taking into account the use of respiratory protective devices (RPD). As in previous studies, no simple relationship was found between results by PCOM and ATEM counting methods. Some ACM, such as asbestos-containing plasters, generated very high dust levels, and some techniques generated considerable levels of dust whatever the ACM treated. On the basis of these observations, recommendations were made to measure and control the occupational exposure limit. General prevention measures to be taken during work with ACM are also suggested. Finally, it is necessary to continue acquiring knowledge, in particular regarding RPD and the dust levels measured by ATEM for the activities not evaluated during this study.

Taking Multiple Exposure Into Account Can Improve Assessment of Chemical Risks.

During work, operators may be exposed to several chemicals simultaneously. Most exposure assessment approaches only determine exposure levels for each substance individually. However, such individual-substance approaches may not correctly estimate the toxicity of 'cocktails' of chemicals, as the toxicity of a cocktail may differ from the toxicity of substances on their own. This study presents an approach that can better take into account multiple exposure when assessing chemical risks. Almost 30000 work situations, monitored between 2005 and 2014 and recorded in two French databases, were analysed using MiXie software. The algorithms employed in MiXie can identify toxicological classes associated with several substances, based on the additivity of the selected effects of each substance. The results of our retrospective analysis show that MiXie was able to identify almost 20% more potentially hazardous situations than identified using a single-substance approach. It therefore appears essential to review the ways in which multiple exposure is taken into account during risk assessment.

First Metagenomic Survey of the Microbial Diversity in Bioaerosols Emitted in Waste Sorting Plants.

Waste sorting activities are source of occupational bioaerosol exposures that are associated with several health disorders. New analytical tools, based on next-generation sequencing (NGS) technologies, provide powerful methods to assess the microbial composition of bioaerosols. The objectives of the study were (i) to assess the feasibility and the repeatability of NGS-based biodiversity measurements and (ii) to study the microbial biodiversity using NGS in bioaerosols emitted in a waste sorting plant (WSP). Three stationary parallel samples were collected in a sorting cabin using closed-face cassettes equipped with polycarbonate membranes. Bacterial and fungal diversity was assessed by sequencing 16S and 18S rDNA genes using either Illumina sequencing or 454 pyrosequencing methods. At sampling point, airborne bacteria were dominated by Proteobacteria, Firmicutes, and Actinobacteria with prevailing genera assigned to unclassified Enterobacteriaceae, Staphylococcus, Acinetobacter, Leuconostoc, Pseudomonas, and Lactobacillus. Airborne fungi were dominated by Ascomycota with prevailing genera assigned to Penicillium, Aspergillus, Rhizopus, Wallemia, and Hemicarpenteles. The NGS biodiversity measurements revealed a higher biodiversity bioaerosols that previously reported for WSP in studies carried out using culture methods followed by identification of microorganisms. These results provide the first survey about taxonomic biodiversity in bioaerosols from WSPs using high-throughput sequencing.

Exposure to hazardous substances in Cathode Ray Tube (CRT) recycling sites in France.

The Waste Electrical and Electronic Equipment (WEEE) or e-waste recycling sector has grown considerably in the last fifteen years due to the ever shorter life cycles of consumables and an increasingly restrictive policy context. Cathode Ray Tubes (CRTs) from used television and computer screens represent one of the main sources of e-waste. CRTs contain toxic materials such as lead, cadmium, barium, and fluorescent powders which can be released if recycling of CRTs is not appropriate. Exposure to these harmful substances was assessed in nine workshops where CRT screens are treated. Particulate exposure levels were measured using a gravimetric method and metals were analysed by plasma emission spectrometry. The maximum levels of worker exposure were 8.8mg/m(3), 1504.3µg/m(3), 434.9µg/m(3), 576.3µg/m(3) and 2894.3µg/m(3) respectively for inhalable dust, barium, cadmium, lead and yttrium. The maximum levels of airborne pollutants in static samples were 39.0mg/m(3), 848.2µg/m(3), 698.4µg/m(3), 549.3µg/m(3) and 3437.9µg/m(3) for inhalable dust, barium, cadmium, lead and yttrium. The most harmful operations were identified, and preventive measures for reducing the chemical risk associated with screen recycling were proposed. Workplace measurements were used to define recommendations for reducing the chemical risks in CRT screens recycling facilities and for promoting the design and development of "clean and safe" processes in emerging recycling channels.

TEXAS: a Tool for EXposure ASsessment-Statistical models for estimating occupational exposure to chemical agents.

Measurements of occupational exposure to chemical agents are performed by sampling and analyzing workplace atmospheres. In France, this is done by the industrial hygienists of the prevention network of the Social Security Service, who collect and then enter the data in the COLCHIC database. More than 900000 measurements performed in French companies over the past 25 years have been collected. Using this amount of data is major challenge for obtaining knowledge and predicting occupational exposures. This study presents the way in which statistical models are built and used on the basis of almost 19000 recent measurements of 26 frequent chemical substances. For a given substance, the models use 13 exposure determinants as inputs, such as the task performed, the occupation of the operator or the type of process employed. The models permit to estimate two parameters: the geometric mean and geometric standard deviation. These parameters are used to build an exposure profile. By combining them with the limit value, an exposure index is estimated using a Bayesian network. A decision rule based on the interpretation of this probability is proposed to qualify the predicted situation as 'well-controlled situation', 'controlled situation', and 'poorly controlled situation'. On the basis of this decision rule, 62% of predictions are true for all substances confounded, an average of 36% of predictions are approximate and only 2% of them are wrong. The result of this study led to the development of a pragmatic software tool named TEXAS, tool for exposure assessment, which enables industrial hygienists to obtain a rapid estimation of the level of exposure control as a function of simple determinants of work situations.

Occupational exposure in the fluorescent lamp recycling sector in France.

The fluorescent lamp recycling sector is growing considerably in Europe due to increasingly strict regulations aimed at inciting the consumption of low energy light bulbs and their end-of-life management. Chemical risks were assessed in fluorescent lamp recycling facilities by field measurement surveys in France, highlighting that occupational exposure and pollutant levels in the working environment were correlated with the main recycling steps and processes. The mean levels of worker exposure are 4.4 mg/m(3), 15.4 µg/m(3), 14.0 µg/m(3), 247.6 µg/m(3), respectively, for total inhalable dust, mercury, lead and yttrium. The mean levels of airborne pollutants are 3.1mg/m(3), 9.0 µg/m(3), 9.0 µg/m(3), 219.2 µg/m(3), respectively, for total inhalable dust, mercury, lead and yttrium. The ranges are very wide. Surface samples from employees' skin and granulometric analysis were also carried out. The overview shows that all the stages and processes involved in lamp recycling are concerned by the risk of hazardous substances penetrating into the bodies of employees, although exposure of the latter varies depending on the processes and tasks they perform. The conclusion of this study strongly recommends the development of a new generation of processes in parallel with more information sharing and regulatory measures.

Assessment of occupational exposure to chemicals by air sampling for comparison with limit values: the influence of sampling strategy.

This study was aimed at quantifying the impact of sampling duration and the number of measurements taken on the quality of assessing occupational exposure to toluene. To this end, a measurement database was built, based on four campaigns carried out in an industrial printing facility. Five homogeneous exposure groups (HEGs) were set up and between 120 and 290 individual measurements lasting from 2 to 8 h were collected for each of them. These measurements were performed with the objective of comparing them to the 8-h Occupational Exposure Limit (8-h OEL). The resulting data were used to define a reference exposure profile per HEG: the 'gold standard'. This exposure profile corresponds to a log-normal distribution of measurements from which compliance/non-compliance with the 8-h OEL decision is derived. To simulate the possible sampling strategies used by industrial hygienists, six scenarios were defined, each containing a different number of measurements: 2, 3, 4, 6, 9, and 12 measurements performed per HEG, over different working days and different seasons of the year. The measurement values per scenario were simulated by sampling from the real measurement per HEG. For each scenario, 1000 simulated exposure profiles and corresponding simulated compliance decisions were computed. They were compared to the gold standard compliance decision using statistical indicators. Three methods were used for computing the simulated compliance decision: (i) the 95th percentile must be lower than the 8-h OEL, (ii) the exceedance fraction with respect to the 8-h OEL must be <0.1% (as defined by standard CEN 689, Appendix D), and (iii) the 70% upper confidence limit of the exceedance fraction with respect to the 8-h OEL must be <5% (as defined by French regulations). The results show that exposure assessment quality increases with both the number of measurements and sampling duration when using the 95th percentile and exposure assessment based on French regulations, whereas it decreases when using the standard. Moreover, guidelines for the efficient evaluation of chemical exposure in the workplace can be drawn up to help professional occupational hygienists. Indeed, boundaries can be recommended regarding the number of measurements and sampling duration necessary to obtain a reliable exposure assessment while minimizing effort devoted to sampling and analysis.

Exposure to airborne endotoxins among sewer workers: an exploratory study.

Exploratory bioaerosol sampling was performed in order to assess exposure to airborne endotoxins during sewer work. Personal samples were collected in underground sewer pipes using 37-mm closed-face cassettes containing fibreglass filters (CFC-FG method) or polycarbonate filters (CFC-PC method). Endotoxins were quantified using the limulus amoebocyte lysate assay. Concentrations of airborne endotoxins at sewer workplaces (16-420 EU m(-3)) were higher than those measured outside the sewer network (0.6-122 EU m(-3)). Sewer worker exposure to airborne endotoxins depended on the workplace and on the tasks. Exposure levels were the highest for tasks involving agitation of water and matter, especially for 'chamber cleanup' and 'pipes cleanup' with a high-pressure water jet. Airborne endotoxin levels at the workplace tended to be higher when CFC-FG was used as the sampling method rather than CFC-PC. The adjusted mean of the measured concentrations for CFC-PC represents 57% of the mean observed with CFC-FG. The number of samples collected in the descriptive study was too low for drawing definitive conclusions and further exposure investigations are needed. Therefore, our exploratory study provides new exposure data for the insufficiently documented sewer working environment and it would be useful for designing larger exposures studies.

A "green route" to propene through selective hydrogen oxidation.

The pros and cons of oxidative dehydrogenation of propane are outlined and a new catalytic system based on metal-doped cerianite catalysts is introduced. These novel materials catalyze the selective combustion of hydrogen from a mixture of hydrogen, propane, and propene at 550 degrees C. This gives three key advantages: energy is supplied directly where needed, product separation is made easier, and the dehydrogenation equilibrium is shifted to the desired products. A set of eighteen doped cerianites was synthesized in parallel, characterized, and screened for activity, selectivity, and stability in a cyclic redox system. The best results were obtained with Ce(0.89)Cr(0.02)Fe(0.09)O(2), Ce(0.98)Sn(0.02)O(2), and Ce(0.96)Cu(0.02)Zn(0.02)O(2), which gave 98 %, 91 %, and 98 % selectivity, respectively. Ce(0.89)Cr(0.02)Fe(0.09)O(2) also shows excellent stability in over 120 cycles (66 h on stream at 550 degrees C). Importantly, these doped cerias are monophasic crystalline materials. The dopants are incorporated as solid solutions throughout the fluorite lattice. This means that these catalysts are very stable (they do not sinter during reduction) as opposed to traditional supported metal oxides. The results show that both activity and selectivity towards hydrogen combustion can be tuned (increased or decreased) by selecting the appropriate dopant. Furthermore, the trends in selectivity differ from those measured on supported oxides of the same elements, which indicates that these novel materials indeed contain unique active sites. The factors governing selectivity towards hydrogen oxidation and the nature of the active site are discussed.

Development of an integrated informatics toolbox: HT kinetic and virtual screening.

We discuss thoroughly aspects and issues for the development of a bespoke, but generic, electronic infrastructure designed to cope with the dynamic in high-throughput experimentation and knowledge management, is applicable to large or contract research organizations. We present the first generation of an informatics platform developed for TOPCOMBI, a research project funded by the European Commission for Nanotechnology and Nanoscience. It is composed by an infrastructure and a collection of modules dealing with laboratory analytics, robotics, data handling and analytics, optimization, in-database processing and visualization, which are developed collegially by the partners of the Consortium. This best-of-breed informatics system enables the capture and the re-usage of processes and methodologies, i.e. process and data flows, using the workflow paradigm. Complex workflows designed by power users can be eventually used by either other domain experts or by novices through a web portal. Workflows can also be run interactively to allow visual analytics for instance, or automatically. We present two case studies dealing with the kinetic study of glycerol catalytic oxidation using parallel equipments, and a novel, fully integrated QSAR applied in heterogeneous catalysis, respectively.

Optimisation methodologies and algorithms for research on catalysis employing high-throughput methods: comparison using the Selox benchmark.

The Selox is a catalytic benchmark for the selective CO oxidation reaction in the presence of H(2), in the form of mathematical equations obtained via modelling of experimental results. The optimisation efficiencies of several Global Optimisation algorithms were studied using the Selox benchmark. Genetic Algorithms, Evolutionary Strategies, Simulated Annealing, Taboo Search and Genetic Algorithms hybridised with Knowledge Discovery procedures were the methods compared. A Design of Experiments search strategy was also exemplified using this benchmark. The main differences regarding the applicability of DoE and Global optimisation techniques are highlighted. Evolutionary strategies, Genetic algorithms, using the sharing procedure, and the Hybrid Genetic algorithms proved to be the most successful in the benchmark optimisation.

Computational methods in the development of a knowledge-based system for the prediction of solid catalyst performance.

The objective of this work is the construction of a correlation between characteristics of heterogeneous catalysts, encoded in a descriptor vector, and their experimentally measured performances in the propene oxidation reaction. In this paper the key issue in the modeling process, namely the selection of adequate input variables, is explored. Several data-driven feature selection strategies were applied in order to obtain an estimate of the differences in variance and information content of various attributes, furthermore to compare their relative importance. Quantitative property activity relationship techniques using probabilistic neural networks have been used for the creation of various semi-empirical models. Finally, a robust classification model, assigning selected attributes of solid compounds as input to an appropriate performance class in the model reaction was obtained. It has been evident that the mathematical support for the primary attributes set proposed by chemists can be highly desirable.

Detection of 28 neurotransmitters and related compounds in biological fluids by liquid chromatography/tandem mass spectrometry.

This work presents two liquid chromatography/tandem mass spectrometry (LC/MS/MS) acquisition modes: multiple reaction monitoring (MRM) and neutral loss scan (NL), for the analysis of 28 compounds in a mixture. This mixture includes 21 compounds related to the metabolism of three amino acids: tyrosine, tryptophan and glutamic acid, two pterins and five deuterated compounds used as internal standards. The identification of compounds is achieved using the retention times (RT) and the characteristic fragmentations of ionized compounds. The acquisition modes used for the detection of characteristic ions turned out to be complementary: the identification of expected compounds only is feasible by MRM while expected and unexpected compounds are detected by NL. In the first part of this work, the fragmentations characterizing each molecule of interest are described. These fragmentations are used in the second part for the detection by MRM and NL of selected compounds in mixture with and without biological fluids. Any preliminary extraction precedes the analysis of compounds in biological fluids.