Biological Tolerance Value Research Articles

Relationship between personal-sampled air lead and blood lead in low-lead-exposure workers in Japan to apply multiple regression models determining permissible air lead concentration.

ObjectivesWe investigated the relationship between lead in air (Pb‐A) measured by personal sampling and blood lead (Pb‐B) in workers with relatively low lead exposure to estimate the permissible air concentration of lead corresponding to the biological tolerance value of Pb‐B of 15 µg/dL.MethodsWe collected air samples at a lead‐acid battery factory in Japan by personal sampling devices attached to 32 workers (19 males and 13 females) and measured Pb‐A by a graphite furnace atomic absorption spectrophotometer in 2017‐2020. In addition, we collected information on age, smoking habits, Pb‐B, and urinary δ‐aminolevulinic acid from the records of medical examinations for lead poisoning. Samples were collected two times from four workers, resulting in 36 data sets.ResultsBefore analyses, we excluded four inappropriate data sets. The levels of Pb‐A in the factory and Pb‐B in the workers were almost under the current permissible limits. Multiple regression models showed significant correlations between Pb‐B and Pb‐A, and sex, and borderline significance between Pb‐B and age. Based on them, we calculated Pb‐A corresponding to Pb‐B 15 μg/dL, and obtained similar values to the current occupational exposure limit (OEL) of 30 μg/m3, with slight variation between sex and age.ConclusionThese results validate OEL, although supplementary conditions in terms of sex and age may be necessary.

The Health Effects of Aluminum Exposure.

Aluminum is regularly taken up with the daily diet. It is also used in antiperspirants, as an adjuvant for vaccination, and in desensitization procedures. In this review, we present the scientifically documented harmful effects of aluminum on health and the threshold values associated with them. This review is based on publications retrieved by a selective search of the PubMed and SCOPUS databases on the topic of aluminum in connection with neurotoxicity, Alzheimer's disease, and breast cancer, as well as on the authors' personal experience in occupational and environmental medicine. The reference values for the internal aluminum load (<15 μg/L in urine, <5 μg/L in serum) are especially likely to be exceeded in persons with occupational exposure. The biological tolerance value for occupational exposure is 50 μg of aluminum per gram of creatinine in the urine. For aluminum welders and workers in the aluminum industry, declining performance in neuropsychological tests (attention, learning, memory) has been found only with aluminum concentrations exceeding 100 μg/g creatinine in the urine; manifest encephalopathy with dementia was not found. Elevated aluminum content has been found in the brains of persons with Alzheimer's disease. It remains unclear whether this is a cause or an effect of the disease. There is conflicting evidence on carcinogenicity. The contention that the use of aluminum-containing antiperspirants promotes breast cancer is not supported by consistent scientific data. The internal aluminum load is measured in terms of the concentration of aluminum in urine and blood. Keeping these concentrations below the tolerance values prevents the development of manifest and subclinical signs of aluminum toxicity. Large-scale epidemiologic studies of the relationship between aluminum-containing antiperspirants and the risk of breast cancer would be desirable.

Biomonitoring in der Arbeitsmedizin

Biomonitoring is an essential occupational-medical instrument for assessing the exposure of chemical agents of workers. It is an integral part of preventive medical examinations as far as established analytical procedures and values for evaluating biomonitoring results are available. The DFG Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has published values for evaluating biomonitoring results. Those values are health related values such as the Biological Tolerance Value (BAT) and descriptive values such as the "Biologischer Arbeitsstoff-Referenzwert" (BAR) and Exposure Equivalents for Cancerous Substances (EKA), respectively. Moreover the combination of acceptance values and tolerance values derived by the Committee on Hazardous Substances (AGS) from exposure-risk-relations with the EKA allow the deduction of risk-related values too. The European Biological Limit Value (BLV) and the Biological Guidance Value are also important in the countries of the European Union. The results of a biological monitoring represent person-related data and therefore are subject to the rules on professional confidentiality that apply to physicians.

Clinical Practice of Biological Monitoring

This is the first edition of a concise pocket-size book that aims to provide practical guidance on the selection and interpretation of biological monitoring tests for chemical exposures. The three North American authors represent the perspectives of both occupational and environmental medicine and medical toxicology, and it is the practitioners of these specialities to whom the book is primarily directed. Two short introductory chapters outline the foundations of biological monitoring, providing a useful summary of the principles of test selection, programme design and potential pitfalls when interpreting results. The remainder of the text is structured around short summaries of relevant biological monitoring information for 62 organic and inorganic chemicals. This includes both those where the technique is recommended and those where it is concluded there is no valid method. Each summary is well referenced and concludes with a recommendation on best test (where identified), analyte, matrix, collection timing and ‘level of concern’, defined by the authors as a potential indicator of breach of workplace controls or an indication for further workplace investigation. There appears to be some variation in how level of concern is derived by the various contributing authors. Most seem to apply the American Conference of Government Industrial Hygienist Biological Exposure Index, where one exists, although this is not consistent (e.g. the blood lead level of concern is set at an unexplained 15 μg/dl for adults). Perhaps this could be tightened up in the second edition by adding some notes on the rationale used to set levels of concern for each substance. The Deutsche Forschungsgemeinschaft Biological Tolerance (BAT) and EKA (exposure equivalents for carcinogenic substances) values are also referenced, but not the UK Health and Safety Executive Biological Monitoring Guidance Values. Overall, this is a useful quick reference resource for the busy occupational health practitioner faced with a biological monitoring query, but would necessitate searching more detailed texts to provide all the information needed when setting up a programme for a specific chemical from scratch. However, UK practitioners are likely to find all the equivalent information they require more helpfully presented and in a UK regulatory context in the excellent Health and Safety Laboratory free publication for its customers, Guidance on Laboratory Techniques in Occupational Medicine, 11th edition, 2009.

Classification of skin sensitizing substances: A comparison between approaches used by the DFG-MAK Commission and the European Union legislation

A systematic classification of substances (or mixtures of substances) with regard to various toxicological endpoints is a prerequisite for the implementation of occupational safety strategies. As its principal task the “Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area” of the “Deutsche Forschungsgemeinschaft” (DFG-MAK Commission) derives and recommends maximum workplace concentrations and biological tolerance values (MAK and BAT values) based exclusively on scientific arguments. Several endpoints are evaluated separately in detail, e.g. carcinogenicity, risks during pregnancy, germ cell mutagenicity or contribution to systemic toxicity after cutaneous absorption. Skin- and airway sensitization is also considered; the present paper focuses on these two endpoints.

Lead Poisoning Due to Adulterated Marijuana in Leipzig Indication for chelator therapy should be defined critically: Indicative of Intoxication

The article highlights the fact that classic lead intoxication may be seen even in the 21st century. However, the article also highlights the difficulties that many clinicians experience when interpreting biomonitoring results. The clinical finding, the medical history, and the laboratory measurements are indicative of the diagnosis. Exceeding threshold values by itself does not mean intoxication. The biological tolerance value (BAT) for blood lead concentrations was evaluated in 1981 at 700 µg/L for whole blood. Because of long term effects, the BAT value was lowered to 400 µg/L whole blood by the Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area. In 2006, lead was included in the cancer category 2 (animal experiment). To prevent non-carcinogenic effects, a biological reference value was formulated at the level of the former BAT value. For women of childbearing age, no reference value could be defined because of the teratogenic effects of lead. The values for women are therefore oriented along the environmental pollution values for the general population. The reference value in 1981 was 300 µg/L in whole blood. As the environmental pollution for the general population decreased the value for women younger than 45 years was adapted to 100 µg/L whole blood in 2003. To talk about lead intoxication by definition in a scenario of the HBM II value being exceeded by 250 µg/L cannot be regarded as an adequate interpretation of a measuring result. Even in the 21st century, blood lead concentrations of >700 µg/L are measured in German work places, without those exposed showing any symptoms of manifest lead intoxication.

Biological tolerance values: change in a paradigm concept from assessment of a single value to use of an average

Since 1981 biological tolerance values for occupational exposure (BAT values) have been published in the List of MAK and BAT Values of the Deutsche Forschungsgemeinschaft (DFG). In 2007 the list includes threshold limit values for more than 90 substances. The BAT value was defined as the maximum permissible quantity of a chemical substance or its metabolites or the maximum permissible deviation from the norm of biological parameters induced by these substances. The biological limit values derived by other commissions (ACGIH, SCOEL) are to be understood as averages, which may well be exceeded individually, in contrast to the BAT values that were defined as ceiling values and thus did not allow an excess of values in the individual employee. The DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has now revised the concept of biological limit values. The BAT value describes the concentration of a chemical substance, of its metabolites or of an effect indicator in appropriate biological material derived by occupational medical and toxicological criteria, at which the health of an employee is usually not affected, even after repeated or long-term exposure. In this case, derivation of the BAT value is based on the average internal exposures. With this redefinition of the German BAT value, it will be possible to better harmonize the values with those provided by other commissions, which are also based on an average concept.

Intervention study on acquired color vision deficiencies in styrene-exposed workers.

The main aim of the study was to examine the possible effects of occupational exposure to styrene on color vision function and the course after reduction of exposure. Color vision function was examined in 22 styrene-exposed laminators and 11 control subjects at a boat manufacturing plant. The Lanthony D-15 desaturated panel was used to test acquired dyschromatopsia. In all, six examinations were performed: Monday morning and Thursday afternoon of the same week, before and immediately after a vacation of 4 weeks (altogether, phase 1), and approximately 10 months later (phase 2), after the exposure level of styrene had been reduced. Styrene uptake was objectified by biological monitoring measuring the metabolites mandelic acid and phenylglyoxcylic acid in urine samples taken on Thursday afternoon. In both Thursday examinations, styrene-exposed workers had higher color confusion index (CCI) values compared with controls, which indicated quantitative color vision loss. After an exposure-free period of 4 weeks, a significant decrease of CCI values to normal range was found in laminators. Reexamination 10 months later showed also lower CCI values in exposed workers, indicating a dose-effect relationship. Abnormal CCI values occurred primarily in subjects with an excretion of approximately 500 to 600 mg mandelic acid plus phenylglyoxcylic acid per gram creatinine or more. We concluded that styrene-induced color vision dysfunction is reversible after an exposure-free interval of 4 weeks. The current Biological Tolerance Value of 600 mg mandelic acid plus phenylglyoxcylic acid per gram creatinine, as used in Germany, protects styrene-exposed workers from this subclinical effect.

Biological monitoring of standardized exposure to ethylbenzene: evaluation of a biological tolerance (BAT) value.

The results of standardized 8 h lasting exposures of n = 18 volunteers to ethylbenzene (EthBz) at levels of 25 and 100% of the maximum allowable concentrations at the workplace (MAK) value of 100 ppm as well as the results of field studies are considered to evaluate a biological tolerance (BAT) value for EthBz. On the basis of the relationship between the external and internal exposure a BAT value of 1.5 mg/l has been set for the EthBz concentration in blood as the most sensitive and specific parameter of exposure to this aromatic hydrocarbon. The interpretation of EthBz blood values has to take into account the short half-life of t1/2 = 0.5 +/- 0.08 h in the first hour after the end of exposure in which this aromatic hydrocarbon is eliminated from the blood. The additional determination of the EthBz metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA), respectively, excreted in post shift urine as well as in urine samples at the beginning of the next shift shows good correlations with the external exposure. The biological half-life of MA was calculated to t1/2 = 5.3 +/- 1.1 h. Because the time of sampling can vary the relationship between the levels of MA to PGA the total concentration of the excreted metabolites depends less on this influence and is therefore better suited for monitoring exposed persons. On the basis of the standardized experiments a BAT value has been proposed of 2 g MA plus PGA corrected per gram creatinine. Both BAT values are adjusted to data which result from earlier standardized exposures during 30 min to EthBz under physical activity of 50 watt on a bicycle ergometer.

An analysis of criteria for biological limit values developed in Germany and in the United States.

The biological tolerance values established by the German Research Foundation and the biological exposure indices developed by the American Conference of Governmental Hygienists represent two extensive lists of occupational exposure guidelines for use in biological monitoring. Although there is substantial agreement between the two organizations on most points, there are several important differences in the approaches taken in setting of the guideline values. Analysis of these distinctions serves to focus attention on the current issues impeding international agreement over occupational exposure guidelines. Among these issues are (1) the specification of the biological monitoring guidelines as ceiling or average values; (2) whether carcinogenic substances should be treated differently from agents with other toxic outcomes; (3) the method of accounting for variability among individual workers; and (4) the extent to which these guidelines should be extended to include genetic markers, indicators of susceptibility, or indicators of early biological response.

Consideration of individual susceptibility in adverse pesticide effects

The modern environmental awareness leads to the realisation that the human metabolism is stressed by a huge number of chemical substances. Generally, these background exposures, consisting predominantly from natural and partly from industrial as well as life style sources, are tolerated without any adverse effects. Pesticides are chemicals intentionally introduced to the environment and have become necessities in modern agriculture as well as in indoor pest control. Their residues, therefore, is attracting more and more concern. For the majority of pesticides neither occupational nor environmental medical risk evaluations are so far available. Therefore, at the moment the occupational as well as the environmental supported preventive concept may only be achieved, if binding instructions upon experience and guide values are developed for the assessment of the individual risk of handling pesticides. In the occupational and environmental pesticide prophylaxis the ubiquitous background exposure levels in consideration with individual susceptibility factors should be recommended as provisional biological tolerance guide values. The suitability of this guide values concept for pesticides is demonstrated by determining the background exposure and the biomarkers of susceptibility of 250 unexposed persons as well as of more than 1200 occupationally exposed persons. As a result, a significant dependence of their health fidelity from the background exposure profile impressed on the individual polymorphism of the key enzymes was observed. Especially, the cumulative adducts of electrophilic substances and their metabolites with macromolecules like HSA and Hb turned out to be sensitive markers for the capacity of the individual metabolic rate. For alkylating and arylating pesticides the observed interindividual susceptibility to their adverse effects depends on the variability of the individual ‘toxifying’ and ‘detoxifying’ metabolic rates. Until scientific evaluation of official biological tolerance values for pesticides is carried out, it is advisable for risk prophylaxis to orientate the assessment of any individual tolerable stress and strain from pesticides to the synergism between background exposure, life style factors and biomarkers of specific susceptibility. They may be examined by a monitoring of conjugates and polymorphism marked by the individual metabolic rate. The monitoring and surveillance of pesticide exposures is mainly introduced by the recommendation of tolerable biological values from the reference value concept. This concept is an essential contribution to an objective risk discussion with regard to individual stress and strain profiles in environmental exposure scenarios.

Biological monitoring: the role of toxicokinetics and physiologically based pharmacokinetic modeling.

This short review outlines the contribution of modeling techniques, particularly physiologically based pharmacokinetic (PBPK) modeling, in promulgating biological monitoring as a practical tool for the occupational health professional. The impact of modeling techniques is discussed in helping to establish the relevant biomarkers to measure, the appropriate time of sampling, and the relationship between atmospheric exposure limits and concentration of biological analyte. Of particular interest is the use of "population" PBPK techniques. These can explore the influence of physiological differences between workers or of particular susceptible subgroups (e.g., pregnant women, breast-feeding mothers, and infants) on the relationship between atmospheric exposure levels and biomarker concentration. Such techniques will become more widely used as biological monitoring guidance values (e.g., biological exposure indices, biological tolerance values) are increasingly established by various international professional and regulatory bodies.

S-p-toluylmercapturic acid in the urine of workers exposed to toluene: a new biomarker for toluene exposure.

A mercapturic acid attached to the aromatic ring of toluene was for the first time detected in human urine as a metabolite of toluene. Since the metabolism of toluene is usually considered to take place at the side-chain, this gives, besides the biosynthesis of cresols, a further hint of a metabolic conversion of the aromatic system. We examined a group of 33 workers occupationally exposed to toluene, determining the concentrations of toluene in ambient air and in whole blood, o-cresol and hippuric acid in urine and p-toluylmercapturic acid (p-TMA) in urine. All blood and urine samples were collected post-shift. The renal excretion of S-p-toluylmercapturic acid showed highly significant correlations with established parameters of a biological monitoring of toluene. The median ambient air concentration was 63 ppm, ranging from 13 to 151 ppm, the median concentration of toluene in whole blood was 804 microg/l, corresponding to median urinary concentrations for o-cresol of 2.3 mg/l, hippuric acid of 2.3 g/l and p-TMA of 20.4 microg/l. p-TMA was not detectable in urine samples of a control group of 10 non-exposed persons. Both the German Biological Tolerance Values (BAT-values) for toluene in blood (1000 microg/l) and o-cresol in urine (3 mg/l) correspond to a mean p-TMA elimination of approximately 50 microg/l, and thus are in agreement with each other. According to our results p-TMA reflects internal toluene exposure diagnostically sensitive and specifical. With the developed analytical procedure we determined a median benzylmercapturic acid (BMA) concentration of 190 microg/l in the urine samples of the toluene exposed persons. We also determined a median BMA concentration of 30 microg/l in the control samples of non-exposed persons. However, these results are preliminary and require further confirmation as the reliability of the method was determined only for p-TMA.

N-acetyl-S-(dichlorophenyl)cysteines as suitable biomarkers for the monitoring of occupational exposure to 1,2-dichlorobenzene.

A method has been developed for the simultaneous analysis of the isomeric N-acetyl-S-(dichlorophenyl)cysteines (also known as dichlorophenylmercapturic acids, DCPMAs) in urine. This procedure allows the determination of 2,3- and 3,4-DCPMAs at the concentrations expected in the urine samples of employees occupationally exposed to 1,2-dichlorobenzene (1,2-DCB). The results of a 1,2-DCB exposure study under standardized conditions show a first-order kinetic for the excretion of DCPMAs, as well as acceptable linear correlations between the urinary concentrations of DCPMAs and the amount of inhaled 1,2-DCB. It therefore seems it would be possible to derive a biological tolerance value for 1,2-DCB based on isomeric DCPMAs as analytical parameters.

Occupational chronic exposure to organic solvents. XVI. Ambient and biological monitoring of workers exposed to toluene.

Ambient air and biological monitoring of an occupational toluene exposure was carried out on a group of 33 workers. The biological monitoring of the workers was based on determination of the concentration of toluene in blood and on quantification of the urinary metabolites o-cresol and hippuric acid. All blood and urine samples were collected post-shift. The average toluene concentration in the workplace air was 65 ppm, ranging from 13 to 151 ppm. AN average concentration of toluene in the blood of 911 microns/1 was found, corresponding to an average urinary concentration of 2.9 mg/1 (2.3 mg/g creatinine) o-cresol and 2.4 g/l (1.9 g/g creatinine) hippuric acid. Both urinary metabolites can be correlated with the concentration of toluene in ambient air and blood, respectively. The results of our study indicate that the determination of the urinary o-cresol excretion represents a diagnostically specific and sensitive parameter for the estimation of an individual toluene uptake. In contrast, monitoring of the concentration of hippuric acid in urine cannot be recommended for assessment of individual exposure. To set up a biological tolerance value (BAT) for o-cresol, a urinary concentration of 3 mg/l o-cresol should be in accordance with the current MAK value of 50 ppm toluene.

Book review

VOICES FOR THE EARTH Vital Ideas from America's Best Environmental Writers Daniel D. Chiras (Editor) and the Sustainable Futures Society Deutsche Forschungsgemeinschaft: “List of MAK and BAT Values 1994: Maximum Concentrations and Biological Tolerance Values at the Workplace”, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Report No. 30, VCH, Weinham, Germany, 1994. Henschler, D., and Lehnert, G. (eds.): “Biological Exposure Values for Occupational Toxicants and Carcinogens: Critical Data Evaluation for BAT and EKA Values”, Volume I, Deutsche Forschungsgemeinschaft Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, VCH, Weinham, Germany, 1994.

Lead exposure in starter battery production: investigation of the correlation between air lead and blood lead levels.

The threshold limit value (TLV) for lead (in Germany, the MAK value) is based on a certain blood lead concentration (in Germany BAT value = biological tolerance value for working materials) that is not to be exceeded; thereby a statistically significant association between air lead (PbA) and blood lead (PbB) is assumed. On the basis of a 10-year period of (1982-1991) biological and ambient monitoring of 134 battery factory staff and their workplaces, a PbA/PbB correlation with the regression equation PbB = 62.183 + 21.242 x Log 10 (PbA) (n = 1089, r = 0.274, P < 0.001) was calculated. These results are in line with those of several other investigations. The shape of the regression curve and the wide scattering of values led to the assumption that PbA values above the MAK value (0.1 mg/m3) do not necessarily result in increased PbB values. Similarly, PbA values lower than the MAK value do not guarantee PbB levels below the BAT value in every case. These observations are influenced by numerous confounders and intervening variables. It is concluded that lowering MAK values as a consequence of lowering BAT values is not mandatory.

Molecular dosimetry of 2,4-difluoroaniline in humans and rats by determination of hemoglobin adducts.

Exposure to 2,4-difluoroaniline (DFA) was monitored by GC-MS of DFA adducts bound to hemoglobin (Hb). In two studies, involving 20 and 16 workers potentially exposed to low concentrations of DFA, median concentrations of 10 (range 1-83) and 20 (range 4-322) pmole/g Hb were found, respectively. For better interpretation of these results, the in vivo binding of DFA to Hb was investigated. DFA was administered orally at doses of 0, 0.078, 0.775, 7.75, and 77.5 mumole/kg/day, to 10 male and 10 female Fischer 344 rats for 10 consecutive days (2 rats/sex/dose group). A linear relation between dose and adduct concentration was observed. At the two lowest doses (0.078 and 0.775 mumole/kg/day) no methemoglobinemia was observed, but adducts could easily be measured. At these doses, the mean adduct levels were in the same range as found in the human studies. As yet, no occupational exposure limit for DFA has been established. The German biological tolerance value (BAT-value) for aniline was set at 7.2 nmole/g Hb. This BAT-value is based on the relation between methemoglobinemia and adduct formation. The amount of Hb binding by aniline and DFA was found to be similar in the rat. Assuming that this is also the case in humans, the BAT-value for aniline may tentatively be used for DFA as well. In both studies of occupationally exposed workers, the adduct levels were well below this BAT-value.

Analysis in workplace surveillance

The protection of the health against effects of chemical substances which are taken up at the workplace is controlled in Germany by the Gefahrstoffverordnung (Hazardous Substances Ordinance). The protection is based on the adherence to threshold limit values for the concentration of the toxic substance in the air or in body fluids of the human being. The adherence to the Maximum Concentrations at the Workplace (MAK) and the Technical Exposure Limits (TRK) for carcinogenic substances in the air of workplaces is achieved by the continuous measurement of the toxic substance in the air at the workplaces (ambient monitoring). The continuous monitoring of chemical substances and their metabolic products in blood and urine (biological monitoring) guarantees that the Biological Tolerance Values for Working Materials (BAT) and the Exposure Equivalents for Carcinogenic Working Materials (EKA) are adhered to. Ambient monitoring and biological monitoring complement each other with regard to the desired health protection of the individual. The possibilities of modern instrumental analysis guarantee today that practically all toxic substances in the air can be quantitatively determined. As intercomparison programmes show, a lot more could be done concerning the analytical reliability of air analyses. The introduction of laboratory-internal and -external quality control in the laboratory analysing air therefore seems to be of urgent necessity. The accrediting of laboratories and the use of reliable analysis procedures alone is not sufficient to guarantee the analytical reliability of the results. By means of biological monitoring today very many toxic substances in blood and urine can be routinely determined. An effective quality control prescribed by the Hazardous Substances Ordinance allows reliable analysis results up to the ppt-range. Certain groups of substances, such as e.g. many pesticides, are today still beyond the possibilities of biological monitoring. Increasingly methods are being developed which enable the influence of toxic substances on the human body to be quantified. The adducts of carcinogenic working materials at the germ plasm (DNA) or at the haemoglobin open up new perspectives.

Occupational chronic exposure to organic solvents. XIV. Examinations concerning the evaluation of a limit value for 2-ethoxyethanol and 2-ethoxyethyl acetate and the genotoxic effects of these glycol ethers.

Two groups of workers occupationally exposed to glycol ethers in a varnish production plant or the ceramic industry were examined. For 19 persons the external and internal exposure was assessed on the Monday and Tuesday after an exposure-free weekend. In the varnish production area the concentrations of 2-ethoxyethanol (EE), 2-ethoxyethyl acetate (EEAc), and 2-butoxyethanol (BE) in air averaged 2.9, 0.5, and 0.5 ppm, respectively, on the Monday, and 2.1, 0.1, and 0.6 ppm, respectively, on the Tuesday. At the same workplaces the mean urinary 2-ethoxyacetic acid (EAA) and 2-butoxyacetic acid (BAA) concentrations were 53.2 and 0.2 mg/l on Monday preshift and 53.8 and 16.4 mg/l on Tuesday postshift. The results show that glycol ethers are very well absorbed through the skin. Therefore biological monitoring is indispensable. To study the kinetics of the toxic metabolite, 17 persons were examined for their excretion of EAA in urine during an exposure-free weekend. The median values of the calculated half-times were 57.4 and 63.4 h, respectively, which are longer than the values presented in literature until now. According to our calculations the limit value should not exceed 50 mg EAA per liter of urine, which is the current German biological tolerance value (BAT value) for EAA in urine. The maximum concentration value at the workplace (MAK value) for EE and EEAc in air should be revised. Finally, the subjects from the varnish production plant as well as a group of reference persons were studied for cytogenetic effects of glycol ethers (sister chromatid exchange, micronucleus test). Such effects could not be detected.