Health effects of pesticides in the flower-bulb culture in Holland

In a comprehensive project the health risk for workers using pesticides in the flower-bulb culture was addressed in several studies regarding biological monitoring, occupational hygiene and health effects. With respect to biological monitoring, methods were developed for the analysis of metabolites in urine of captan, pirimicarb, zineb and maneb and the soil fumigant dichloropropene. For dichloropropene in a field study a clear relationship was found between the external personal exposure and the excretion of two metabolites (mercapturic acids) in urine. The application technique distinctly influenced the extent of exposure. For the other substances preliminary measurements were performed in the urine of exposed workers; for captan and pirimicarb the methods are promising for further studies of the uptake of these substances under working conditions. In an occupational hygiene study, the dermal exposure due to different application techniques used in crop protection and bulb disinfection was investigated. This resulted in method specific exposure values (grams/field area of bulbs) that showed large differences between the techniques. These exposure values in combination with information on the type of techniques used, the treated area and the frequency of application were used to calculate a personal exposure index (grams/working life); this is an estimate of the potential (external) exposure of individual workers. In an effect study 137 workers who applied pesticides for more than 10 years (average 20 years) in at least bulb disinfection and crop protection (the most important area's of exposure for the growers) were compared to 73 controls. Tests for autonomic and peripheral nerve functions including the distribution of conduction velocities and refractory periods, were applied as well as computerized neurobehavioral tests and electro-encephalography. Significant effects were found on peripheral nerve function parameters, on measures of attention and perceptual coding and on the amount of beta-activity in the EEG; the data suggest that for the majority of subjects these effects are small. No effects were found on liver and renal function and no difference in the prevalence of symptoms that might be ascribed to the usage of pesticides. In a number of exposed workers a cutaneous allergy to pesticides was found. Based on this study, measures are recommended to diminish effectively the exposure to pesticides in this culture.     

Retrospective estimation methods of pesticide occupational exposure]

The extensively growing use of pesticides in the last decades has led to great improvements in agriculture but also to threats for human health. Studying long term effects to assess individual exposures encounters difficulties in exposure assessment. This article summarizes retrospective methods for assessing occupational exposures to pesticides currently used in epidemiological studies. Questionnaires, environmental and biological monitoring constitute direct assessment of exposure, in an individual approach. But the validity of questionnaires is often poor and the metrology rarely reflects past exposures. Some indirect measures have been used together with job exposure matrices. To establish dose-response relationships is important to quantify the risk, but needs accurate exposure assessment based on quantitative indexes.     

Lessons learned for the assessment of children's pesticide exposure: critical sampling and analytical issues for future studies

In this article we examine sampling strategies and analytical methods used in a series of recent studies of children's exposure to pesticides that may prove useful in the design and implementation of the National Children's Study. We focus primarily on the experiences of four of the National Institute of Environmental Health Sciences/U.S. Environmental Protection Agency/ Children's Centers and include University of Washington studies that predated these centers. These studies have measured maternal exposures, perinatal exposures, infant and toddler exposures, and exposure among young children through biologic monitoring, personal sampling, and environmental monitoring. Biologic monitoring appears to be the best available method for assessment of children's exposure to pesticides, with some limitations. It is likely that a combination of biomarkers, environmental measurements, and questionnaires will be needed after careful consideration of the specific hypotheses posed by investigators and the limitations of each exposure metric. The value of environmental measurements, such as surface and toy wipes and indoor air or house dust samples, deserves further investigation. Emphasis on personal rather than environmental sampling in conjunction with urine or blood sampling is likely to be most effective at classifying exposure. For infants and young children, ease of urine collection (possible for extended periods of time) may make these samples the best available approach to capturing exposure variability of nonpersistent pesticides; additional validation studies are needed. Saliva measurements of pesticides, if feasible, would overcome the limitations of urinary metabolite-based exposure analysis. Global positioning system technology appears promising in the delineation of children's time-location patterns.     

Biological markers of solvent exposure

The important limitation of many epidemiologic studies is the relative inaccuracy of the assessment of the magnitude of exposure. For some solvents, the concentration in biological media is an indication of the internal exposure and is an indirect indication of the health risk, at least for acute effects. For long-term effects, e.g., carcinogenicity, biological monitoring data can also be used as showed with the individual occupational data on the level of trichloroacetic acid (TCA) in urine. Occupational epidemiology can improve the methods for the assessment of the actual total exposure and health risk in environmental epidemiology by providing higher dose cohort data.     

Pesticides in house dust from urban and farmworker households in California: an observational measurement study

Background  

Studies report that residential use of pesticides in low-income homes is common because of poor housing conditions and pest infestations; however, exposure data on contemporary-use pesticides in low-income households is limited. We conducted a study in low-income homes from urban and agricultural communities to: characterize and compare house dust levels of agricultural and residential-use pesticides; evaluate the correlation of pesticide concentrations in samples collected several days apart; examine whether concentrations of pesticides phased-out for residential uses, but still used in agriculture (i.e., chlorpyrifos and diazinon) have declined in homes in the agricultural community; and estimate resident children's pesticide exposures via inadvertent dust ingestion.     

Environmental exposure assessment in European birth cohorts: results from the ENRIECO project

Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.     

Assessment of exposure to chloramphenicol and azathioprine among workers in a South African pharmaceutical plant

There have been very few published studies that have evaluated exposure to myelotoxic drugs among production workers in pharmaceutical plants. Previous studies have focussed mainly on nurses and evaluated exposure to cytotoxic drugs using urine mutagenicity as a marker of exposure. The aim of this study was to evaluate the exposure of workers involved in the production of chloramphenicol and azathioprine. Exposure was evaluated utilising biological monitoring, biological effect monitoring and environmental monitoring. Biological monitoring included plasma chloramphenicol levels, plasma 6-mercaptopurine and urine 6-thiouric acid levels. These were analysed using high performance liquid chromatography. Myelotoxic effect was assessed by measuring the haematological indices of bone. marrow function. The exposed 17 workers were compared to matched controls of equal numbers. Neither substance could be detected in serum nor urine by the analytical methods employed. However, haematological indices demonstrated a significantly decreased mean reticulocyte and neutrophil count in the azathioprine exposed group. Industrial hygiene measurements demonstrated contamination of the air inside the airhood of exposed workers. In conclusion, it is evident that workers involved in the production of both these drugs are at risk of developing adverse health effects. Furthermore, more sensitive analytical methods need to be developed to evaluate absorption of myelotoxic chemicals among occupationally exposed workers.     

Gases and organic solvents in urine as biomarkers of occupational exposure: a review

A brief review of urine analysis in studies of occupational exposure to volatile organic compounds and gases is provided. Analysis of exhaled breath for volatile compounds does not have a long history in occupational medicine. A number of studies has been undertaken since the 1980s, and the methods are well enough accepted to be put forward as biological equivalents of threshold limit values (TLVs) for some volatile organic compounds (VOCs) such as acetone; methanol; methyl ethyl ketone (MEK); methyl isobutyl ketone (MIBK); tetrahydrofurane; dichloromethane. In the last 20 years many scientific articles have shown that the urinary concentrations of unchanged solvents are correlated with environmental exposure and could be used for biological monitoring. The use of urine analysis of unchanged solvents in occupational applications is not yet widespread. Nonetheless, in the short time since its application, a number of important discoveries has been made, and the future appears bright for this branch of analysis. In this paper, the basic concepts and methodology of urine analysis are briefly presented with a critical revision of the literature on this matter. The excretion mechanisms of organic solvents in urine are discussed, with regard to biological variability, and the future directions of research are described.     

The validation of a pesticide exposure algorithm using biological monitoring results

A pesticide exposure algorithm was developed to calculate pesticide exposure intensity scores based on responses to questions about pesticide handling procedures and application methods in a self-administered questionnaire. The validity of the algorithm was evaluated through comparison of the algorithm scores with biological monitoring data from a study of 126 pesticide applicators who applied the herbicides MCPA or 2,4-D. The variability in the algorithm scores calculated for these applicators was due primarily to differences in their use of personal protective equipment (PPE). Rubber gloves were worn by 75% of applicators when mixing and 22% when applying pesticides, rubber boots were worn by 33% when mixing and 23% when applying, and goggles were worn by 33% and 17% of applicators when mixing and when applying, respectively. Only 2% of applicators wore all three types of PPE when both mixing and applying, and 15% wore none of these three types of PPE when either mixing or applying. Substantial variability was also observed in the concentrations of pesticides detected in the post application urine samples. The concentration of MCPA detected in urine samples collected on the second day after the application ranged from less than < 1.0 to 610 microg/L among 84 of the applicators who applied MCPA. The concentrations of 2,4-D detected in the urine samples ranged from less than < 1.0 to 514 microg/L among 41 of the applicators who applied 2,4-D. When categorized into three groups based on the algorithm scores, the geometric mean in the highest exposure group was 20 microg/L compared with 5 microg/L in the lowest exposure group for the MCPA applicators, and 29 microg/L in highest exposure group compared with 2 microg/L in the low exposure group for the 2,4-D applicators. A regression analysis detected statistically significant trends in the geometric mean of the urine concentrations across the exposure categories for both the 2,4-D and the MCPA applicators. The algorithm scores, based primarily on the use of PPE, appear to provide a reasonably valid measure of exposure intensity for these applicators, however, further studies are needed to generalize these results to other types of pesticides and application methods.     

Potential uses of biomonitoring data: a case study using the organophosphorus pesticides chlorpyrifos and malathion

BACKGROUND: Organophosphorus pesticides such as chlorpyrifos and malathion are widely used insecticides. They do not bioaccumulate appreciably in humans and are rapidly metabolized and excreted in the urine. In nonoccupational settings, exposures to these pesticides are typically sporadic and short-lived because the pesticides tend to degrade in the environment over time; however, dietary exposures may be more chronic. Biologic monitoring has been widely used to assess exposures, susceptibility, and effects of chlorpyrifos and malathion; thus, the information base on these compounds is data rich. For biomonitoring of exposure, chlorpyrifos and malathion have been measured in blood, but most typically their urinary metabolites have been measured. For assessing early effects and susceptibility, cholinesterase and microsomal esterase activities, respectively, have been measured. OBJECTIVES: Although many biologic monitoring data have been generated and published on these chemicals, their interpretation is not straightforward. For example, exposure to environmental degradates of chlorpyrifos and malathion may potentially increase f urinary metabolite levels, thus leading to overestimation of exposure. Also, the temporal nature of the exposures makes the evaluation of both exposure and effects difficult. We present an overview of the current biomonitoring and other relevant data available on exposure to chlorpyrifos and malathion and the use of these data in various environmental public health applications.     

A pilot study of workplace dermal exposures to cypermethrin at a chemical manufacturing plant

Exposure during the manufacture of pesticides is of particular concern due to their toxicity and because little is known about worker exposure, since most studies have focused on end-use application within agriculture or buildings. Even though dermal exposure can be expected to dominate for pesticides, little is known about workplace dermal exposures or even appropriate methods for their assessment. The current study begins to address this gap by evaluating alternative methods for assessing dermal exposure at a chemical manufacturing plant. For this pilot study, eight workers were recruited from a U.S. plant that produced the pesticide cypermethrin. Exposure was evaluated using three approaches: (1) survey assessment (questionnaire), (2) biological monitoring, and (3) workplace environmental sampling including ancillary measurements of glove contamination (interior and exterior). In each case, cypermethrin was quantified by enzyme-linked immunosorbent assay (ELISA). Environmental measurements identified two potential pathways of cypermethrin exposure: glove and surface contamination. Workplace exposure was also indicated by urine levels (specific gravity adjusted) of the parent compound, which ranged from 35 to 253 μg/L (median of 121 μg/L) with no clear trend in levels from pre- to post-shift. An exploratory analysis intended to guide future studies revealed a positive predictive association (Spearman correlation, p ≤ 0.10) between post-shift urine concentrations and a subset of survey questions evaluating worker knowledge, attitudes, and perceptions (KAP) of workplace dermal hazards, i.e., personal protective equipment self-efficacy, and inverse associations with behavior belief and information belief scales. These findings are valuable in demonstrating a variety of dermal exposure methods (i.e., behavioral attributes, external contamination, and biomarker) showing feasibility and providing measurement ranges and preliminary associations to support future and more complete assessments. Although these pilot data are useful for supporting design and sample size considerations for larger exposure and health studies, there is a need for validation studies of the ELISA assay for quantification of cypermethrin and its metabolites in urine.     

Measurements of year-long exposure to tree nursery workers using multiple pesticides

A year-long nurseryworker pesticide exposure study was designed to measure and evaluate the exposure occurring to workers who had the potential for simultaneous exposure to multiple pesticides. This four-State study was conducted in five nurseries (four USDA Forest Service and one State) involved in conifer seedling production. Primary comparisons were made among nursery workers in the Pacific northwest and south central United States. Worker exposure was assessed by using patches attached to clothing, handrinse samples and urine excreted from potentially exposed workers. In addition, dislodgeable residue in rinsate from a water wash of pesticide-treated seedlings was also evaluated. Four different groups of field workers, designated as applicators, weeders, scouts and packers, were included. The pesticide absorbed dose, assessed by urine analysis of pesticide metabolites and the deposition of pesticide on patches attached to the clothing of field workers, was monitored as they performed their duties under normal conditions (e.g., typical clothing, pesticide application). Monitoring was performed for the 14 different pesticides which were used in these nurseries. Seven pesticides were studied in more detail using biological monitoring. For these compounds, metabolites known to be excreted in the urine of exposed humans or other mammals were used to estimate the dose of pesticide absorbed by the exposed workers.The highest percentage of positive samples came from dislodgeable residue samples (8.3%) followed by patch samples (3.2%), handrinse (2.9%), and urine samples (1.3%). To summarize the conclusions from the urinary excretion data, 12 of the 73 nursery workers in the study received a low absorbed dose of pesticide. Biological monitoring revealed that three pesticides (benomyl, bifenox and carbaryl) were found in the urine of some of the workers. Of the 3,134 urine samples analyzed there were 42 positive; 11 urine samples were positive for benomyl, while bifenox was responsible for 13 positives and carbaryl accounted for the remaining 18. The 12-week continuous monitoring of urine showed that metabolites of these materials were rapidly excreted; thus, no build-up in the body is anticipated. Margins of Safety (MOS) calculations were made to provide an assessment of the significance of the exposure. Based on the low frequency of positive urine samples in the study, the low levels of metabolites when they were found, their apparent rapid excretion rate and the No Observed Effect Level (NOEL) data, furnished from other sources, nursery worker exposure to pesticides in these conifer nurseries is below health threatening levels.This USDA Forest Service research project was funded by the National Pesticide Impact Program.     

Biomonitoring for chromium and arsenic in timber treatment plant workers exposed to CCA wood Preservatives

This study reports a survey of occupational exposure to copper chrome arsenic (CCA) based wood preservatives during vacuum pressure timber impregnation. The survey involved biological monitoring based on analysis of chromium and arsenic in urine samples collected from UK workers. The aim of the study was to determine the extent of occupational exposure to arsenic and chromium in the UK timber treatment industry. The objectives were to collect and analyse urine samples from as many workers as possible, where CCA wood preservatives might be used, at 6 monthly intervals for 2 years. In addition, to investigate day-to-day variations in urinary excretion of chrome and arsenic by collecting and analysing three samples a week for 3 weeks in subsets of workers and controls (people not occupationally exposed). All urine samples were analysed for chromium and inorganic arsenic. To investigate any residual interference every sample was accompanied by a short questionnaire about recent consumption of seafood and smoking. The analytical methods for arsenic used a hydride generation technique to reduce interference from dietary sources of arsenic and also a technique that would measure total arsenic concentration in urine. The main findings show that workers exposed to CCA wood preservatives have concentrations of inorganic arsenic and chromium in urine that are significantly higher than those from non-occupationally exposed people but below biological monitoring guidance values that would indicate inhalation exposure at UK occupational exposure limits for chromium and arsenic. The effects of consumption of seafood on urinary arsenic were not significant using the hydride generation method for inorganic arsenic but were significant if 'total' arsenic was measured. The 'total' arsenic method could not distinguish CCA workers from controls and is clearly unsuitable for assessment of occupational exposure to arsenic. There was a significant increase in the urinary concentration of chromium in workers over the four sample collection rounds indicating increasing exposure to chromium during the 2 years of the study. This unexpected finding may be worth further investigation. Overall, the study demonstrated the utility of biological monitoring for assessment of occupational exposure to chromium and arsenic.     

Muconic acid determinations in urine as a biological exposure index for workers occupationally exposed to benzene.

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolites with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatography/mass spectrometry assay to detect and quantitate the benzene metabolite, muconic acid, in urine. The internal standard used in the assay, muconic acid-d4, was biosynthesized by F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal standard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benzene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biological monitoring of exposure: trends and key developments

The concept of biological monitoring (BM) has gained the special interest of individual scientists and international organizations. Today, when analytical problems have almost ceased due to new laboratory techniques and quality assurance systems, the methods for interpretation of results have become the most important issue. There are important discrepancies regarding the role of biological monitoring of occupational exposure between Europe and the United States. BM has been an important tool of medical health surveillance in the European countries. In the United States it belongs rather to the field of occupational hygiene. It seems that both the approaches can be accepted. More attention should be paid to the development of the truly health-based biomarkers of exposure based on the dose-effect and dose-response relationships. New areas of application of BM of occupational exposure include determination of DNA and protein adducts, unchanged volatile organic compounds in urine, monitoring of exposure to pesticides, antineoplastic drugs, hard metals, and polycyclic aromatic hydrocarbons. In the general environment BM is the most valuable tool for acquiring knowledge of current levels of internal exposure to xenobiotics, identifying the hot spots and developments in trends of exposure. BM can provide policy makers with more accurate information on the control measures undertaken. At present, the main areas include heavy metals, persistent organic pollutants and pesticides. BM of chemical exposure has become increasingly important in the assessment of the health risk in occupational and environmental medicine. Therefore it would be worthwhile to include BM in the curricula for the training of occupational hygienists.     

Environmental exposure assessment of pesticides in farmworker homes

Farmworkers and their families are exposed to pesticides both at work and in their homes. Environmental exposure assessment provides a means to evaluate pesticides in the environment and human contact with these chemicals through identification of sources and routes of exposure. To date, a variety of methods have been used to assess pesticide exposure among farmworker families, mostly focusing on dust and handwipe samples. While many of the methods are similar, differences in the collection, chemical analysis, and statistical analysis, can limit the comparability of results from farmworker studies. This mini-monograph discusses the strategies used to assess pesticide exposures, presents limitations in the available data for farmworkers, and suggests research needs for future studies of pesticide exposure among farmworker families.     

Assessing diet as a modifiable risk factor for pesticide exposure

The effects of pesticides on the general population, largely as a result of dietary exposure, are unclear. Adopting an organic diet appears to be an obvious solution for reducing dietary pesticide exposure and this is supported by biomonitoring studies in children. However, results of research into the effects of organic diets on pesticide exposure are difficult to interpret in light of the many complexities. Therefore future studies must be carefully designed. While biomonitoring can account for differences in overall exposure it cannot necessarily attribute the source. Due diligence must be given to appropriate selection of participants, target pesticides and analytical methods to ensure that the data generated will be both scientifically rigorous and clinically useful, while minimising the costs and difficulties associated with biomonitoring studies. Study design must also consider confounders such as the unpredictable nature of chemicals and inter- and intra-individual differences in exposure and other factors that might influence susceptibility to disease. Currently the most useful measures are non-specific urinary metabolites that measure a range of organophosphate and synthetic pyrethroid insecticides. These pesticides are in common use, frequently detected in population studies and may provide a broader overview of the impact of an organic diet on pesticide exposure than pesticide-specific metabolites. More population based studies are needed for comparative purposes and improvements in analytical methods are required before many other compounds can be considered for assessment.     

Reference values for metabolites of pyrethroid and organophosphorous insecticides in urine for human biomonitoring in environmental medicine

Pesticides are widely used throughout the world in agriculture to protect crops, and in public health to control diseases transmitted by vectors or intermediate hosts. After the prohibition of organochlorines, such as DDT, today mainly pyrethroids and organophosphorous insecticides are used. With reliable and sensitive analytical methods for detecting metabolites of organophosphorous and pyrethroid insecticides in urinary specimens of the general population several studies have been published on internal exposure to these insecticides of the population in Germany. In total, data on levels of metabolites of organophosphorous acids in urine of about 1200 children and adults have been published, as well as data on levels of pyrethroid metabolites in urine of about 2100 children and adults. In Germany, reference values for environmental pollutants related to the population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency, preferably based on data gained by representative studies. Reference values are defined as the 95th percentile, rounded off within the 95% confidence interval of the population studied. Since there is a need for reference values to characterise the population's exposure to organophosphates and pyrethroids, and since there are different studies available from Germany that agree quite well with data from other industrialised countries, the Commission has derived reference values from the available data, though none of the studies had fulfilled criteria on representativity. Reference values for metabolites of organophosphorous acids are as follows: DMP 135 microg/l, DMTP 160 microg/l and DEP 16 microg/l and for metabolites of pyrethroids: cis-Cl2CA 1 microg/l, trans-Cl2CA 2 microg/l and 3-PBA 2 microg/l. As the volume-related concentrations of organophosphate and pyrethroid metabolites show no significant age-dependence, the reference values derived are not age-stratified. Though based merely on statistical and not on toxicological data, levels analysed above the reference levels, when reliably measured (verified several times), should prompt environmental health practitioners to search for sources, within the bounds of proportionality. In addition to accidental poisoning, possible sources include indoor contamination following improper pest control operations in homes as well as in pets and food products contaminated by these pesticides.     

Trichloroethylene exposure. Biological monitoring by breath and urine analyses.

A mathematical model developed previously has been used to study some aspects of biological monitoring of exposure to trichloroethylene (TRI) by the analysis of this solvent in alveolar air or of its metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA), in urine. Assuming that a biological control must be representative of the time-weighted average concentration (TWA), it was found that sampling for TRI and TCE analyses must be carried out the morning after the exposure being considered. On the other hand, for a TCA analysis, the timing of urine sampling is not a determinant factor. Theortical limit concentrations have been set up for these biological indicators, but it is shown that their application must be restricted to exposures which are quantitatively reproducible from one day to the next. In all other cases, it appears that this monitoring method can lead to errors in the estimated exposure concentrations. A tentative method of biological monitoring is therefore proposed. It is based on the analysis of TCE in the urine or TRI in the alveolar air before and after the exposure being monitored. TCA is not considered to be sensitive enough to variations in the inspired concentration to be used as an indicator of a single exposure risk.