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[Indices of biological monitoring, with special reference to urinalysis of metabolites of organic solvents].

The significance of biological exposure indices, and the methods of biological monitoring of exposure to organic solvents by urinalysis are discussed. The review covers choice of time for urine sampling, correction of the results for urine density, and the urinary concentration of metabolites of non-exposed persons. The method of drawing regression line between concentration of organic solvents in the air and concentration of urinary metabolites in the urine is also described.

Environmental Exposure↗

Biological monitoring of acrylonitrile exposure.

This study reports the results obtained with the environmental and biological monitoring of 34 workers exposed to acrylonitrile (ACN). Occupational exposure was monitored during 8-h work shifts with both active and diffusive personal samplers which yielded comparable results. The median exposure was 78 micrograms/m3. The ACN concentration in urine collected at the end of the work shifts correlated significantly with the environmental exposure. The ACN concentration in the pre-shift urine samples (median 3.6 micrograms/l) was lower than that found in the post-shift samples (median 10.9 micrograms/l), but higher than in the urine of non-exposed people (median 0.45 microgram/l). Smoking is an important confounding factor in monitoring exposure to ACN. The ACN concentration in urine provides reliable information about occupational and non-occupational exposure to ACN. Aspects of the mechanism of ACN excretion in urine are also discussed.

Acrylonitrile↗

Biological monitoring of occupational exposure to benzene and toluene.

This study was carried out to evaluate the biological monitoring of occupational exposure to benzene and toluene in a total number of 31 male exposed workers and 30 control subjects. The present study showed a statistically significant higher level of biological indices of exposure (p < 0.01) of phenol and hippuric acid in urine of workers exposed to benzene and toluene than control subjects. Significant changes (p < 0.05, 0.01) in the levels of hematological and biochemical findings have been observed among exposed workers and control group. In addition, statistically significant higher levels of Mg, Mn and Ca were found among workers exposed to benzene and toluene while statistically significant lower levels of serum iron (p < 0.05) have been observed. No significant variations could be detected in the level of Zn and Cu between exposed and control subjects.

Analysis of Variance↗

[Assessment of occupational exposure to PAH in coke-oven workers of Taranto steel plant through biological monitoring].

OBJECTIVE: This study aims at evaluating the occupational exposure to polycyclic aromatic hydrocarbons (PAH) through biological monitoring and at investigating the influence of selected genetic polymorphisms on the levels of internal dose biomarker. DESIGN: A cross-sectional study has been conducted on the basis of biological measurements in order to evaluate the levels of PAH exposure. SETTING: PAH exposure assessment has been carried out in a coke-oven of one of the largest European steel plants (ILVA, Taranto), in the context of the program of medical surveillance carried in collaboration with the ILVA Occupational Health Service. PARTICIPANTS: 355 coke-oven workers exposed to PAH were enrolled from the 3 batteries of the coke oven plant. Maintenance workers and industrial cleaners were included. MAIN OUTCOME MEASURES: The measurement of urinary levels of 1-hydroxypyrene (1-OHP) as biomarker of internal dose has been carried out, as well as the evaluation of metabolic polymorphisms of the cytochrome P450 1A1 (CYP1A1), glutathione S-transferases mu (GSTM1) and theta (GSTT1) as biomarkers of susceptibility. RESULTS: The median value of urinary 1-OHP was 1,05 microMol/Molcreat. The difference between the groups was statistically significant, with the highest value observed in the maintenance group (median 1,71, range 0,06-14,69 microMol/Molcreat). It is remarkable that 25% of the workers exceeded the proposed benchmark guideline value of2,3 microMol/Molcreat. No statistical difference was found in relation to smoking habits. Workers with GSTT1 null genotype had higher 1-OHP levels than those with wild type (p = 0,06). CONCLUSIONS: The levels of biomarker of internal dose reflect a critical exposure to PAH in the coke-oven plant. Further observations are needed to better investigate the role of GSTT1 on the 1-OHP levels.

Coke↗

Variability in biological monitoring of organic solvent exposure. II. Application of a population physiological model.

A physiological population model is used to study the variability associated with the biological monitoring of solvent exposure. The model consists of a combination of a physiological compartmental model and statistical simulation technique. Variable components considered are: exposure concentration, physical workload, body build, liver function, and renal function. The model is applied to six solvents: trichloroethylene, tetrachloroethylene, methylchloroform, benzene, toluene, and styrene. Biological indicators and air monitoring are compared as predictors of exposure, both external and internal (uptake, brain concentration, reactive metabolite formation). It appears that the choice of the best indicator depends on the type of exposure which is to be predicted. The effects of the various factors, environmental, physiological, or metabolic, are quantified and discussed. It is shown that fluctuation in exposure plays a large part in the final variability of biological indicator results. Further improvements and applications of this population model are considered.

Benzene↗

Biological monitoring of exposure to organophosphate pesticides.

Organophosphates (OPs) are readily absorbed through the skin and biological monitoring is an essential component of any comprehensive assessment of exposure. This paper presents a summary of our experience in a wide range of occupational studies. Additionally, we have conducted studies of non-occupational exposure and human volunteer studies looking at the kinetics of chlorpyrifos, propetamphos, diazinon and malathion. In non-occupationally exposed people, 95% of urinary alkyl phosphates do not exceed 72 micromol/mol creatinine. In occupationally exposed people, the corresponding 95th percentile of total urinary alkyl phosphates is 122 micromol/mol creatinine. In volunteer studies with 1 mg oral doses of chlorpyifos, diazinon and propetamphos the mean peak values were 160, 750 and 404 micromol/mol creatinine, respectively, and were not associated with any reduction in blood cholinesterase activity. The levels of OP metabolites seen in urine from workers potentially exposed to OPs are generally low and unlikely to cause significant reduction in blood cholinesterase activity.

Biomarkers↗

Biological monitoring of occupational exposure to low levels of benzene.

To obtain reference values for the biological monitoring of benzene, the kinetics of benzene were studied in volunteers. Benzene in blood and expired air could easily be followed until the next morning after a 4-h exposure to a benzene concentration of 10 cm3.m-3. Even after exposure to 1.7 cm3.m-3 the benzene levels in the morning blood and expired air samples differed from those in unexposed subjects. One hour after exposure to 10 and 1.7 cm3.m-3 the mean levels of benzene were 238 and 25 nmol.l-1 in blood and 13.2 and 2.5 mumol.m-3 in exhaled air, respectively. It was concluded that, at high benzene levels (approximately 10 cm3.m-3), samples collected 16 h after exposure reflect the body burden of benzene, while at low exposure (< 1 cm3.m-3) samples collected 1 h after exposure may be used to estimate the exposure over the preceding few hours. Exposure to benzene from smoking is a potential confounder in estimating occupational exposure to low levels of benzene.

Adult↗

Biological monitoring of workers exposed to dimethylformamide in a textile polyurethane unit.

Dimethylformamide (DMF) is a universal solvent noted for its solubility in both aqueous and lipid media. It is hepatotoxic, and there are concerns about its carcinogenicity. Our objective was to determine the correlation between air monitoring measurements and biological measurements of a suitable metabolite of DMF in a cohort of operatives in a polyurethane production unit. This was done with a view to assessing how much the inhalation route contributed to total DMF exposure, mainly for control purposes. We investigated the relationship between personal air sample measurements of DMF and biological measurements of N-methylformamide (NMF) in nine adult subjects, recruited across the shifts, with varying levels of exposure to DMF. Personal exposure monitoring was carried out with a low-flow-rate Model 222-4 SKC pump, while post-shift urine samples were obtained for further analysis. Operatives were asked to abstain from consuming alcohol for 24 h before the designated shift, as advised by the laboratory responsible for the analysis of urine samples. We found a very strong statistical association between air sample measurements of DMF and NMF in the urine of the sample population (R(2) = 0.95, P < 0.0001). This study suggests that airborne exposure contributes significantly to elevated levels of NMF and, therefore, indicates that efforts should be concentrated on engineering controls in reducing workplace DMF exposure.

Adult↗

Biological monitoring of environment exposure to safrole and the Taiwanese betel quid chewing.

A rapid and sensitive biological monitoring (BM) method for assessing exposure to the environmental carcinogen safrole has been developed. The method is an isocratic high-performance liquid chromatographic (HPLC) analysis of urinary dihydroxychavicol (DHAB) and eugenol, the urinary metabolites of safrole. Good linearity, precision, and accuracy were demonstrated. A recovery of 98.8 +/- 5.4% (SD, n = 3) was found for DHAB and 84.1 +/- 3.4% (n = 3) for eugenol. The quantitation limits of the method were 8 ng for DHAB and 10 ng for eugenol. The validity of the method was demonstrated by a linear dose-response relationship observed in rats given oral doses of safrole at 30, 75, and 150 mg/kg body weight. The method was also used to monitor the environmental exposure to the Taiwanese betel quid (TBQ) chewing, because TBQ used in Taiwan not only contains areca (betel) nut, slaked lime, and catechu but also Piper betle inflorescence or its leaves. Both of the latter have a high content of safrole. The feasibility of the method to monitor TBQ chewing was demonstrated by an analysis of 153 spot human urine samples. The results showed that the p value of the nonparametric group comparison was < 0.001 for DHAB and 0.832 for eugenol. The TBQ chewers also exhibited a significantly higher rate of urinary DHAB (but not eugenol) than the nonchewers with an odd ratio of 3.47 (95% CI, 1.61-7.51). However, when only the eugenol-positive subjects were taken into analysis, the ratio rose to 24.38 (95% CI, 3.00-197.90).

Administration, Oral↗

Analytical isotachophoresis in biological monitoring of exposure to industrial chemicals.

Isotachophoretic methods for the determination of compounds of interest in biological monitoring are reviewed. The analytes are charged biotransformation products such as acids or amines. Comparisons are made between isotachophoretic methods and other techniques regarding sensitivity, need for preseparation or derivatization and similar technical aspects.

Body Fluids↗

Recent policy and technical developments in biological monitoring in the United Kingdom.

In 1996 the United Kingdom's Health and Safety Executive introduced biological monitoring guidance values for six substances, butoxyethanol, N,N-dimethylacetamide, lindane, methylene-bis(2-chloroaniline), mercury and methylenedianiline. These guidance values were set as either health-based values or hygiene-based values calculate according to the 90th percentile (benchmark concept). Recent technical developments from the Health and Safety Laboratory are described in this paper and include: (i) the use of breath analysis as a useful non-invasive routine monitoring technique; (ii) flow cytometry as a means for measuring different patterns of immune cell activation from workers exposed to respiratory sensitisers when compared with those exposed to chemical irritants; (iii) the use of molecular techniques to explore the possible role of individual susceptibility in the development and severity of glomerulonephritis; (iv) the development of expert systems for predicting the skin permeability of chemicals, and respiratory and skin sensitisation.

Breath Tests↗

Assessment of urban population exposure to trichloroethylene and tetrachloroethylene by means of biological monitoring.

Exposure of the general population to trichloroethylene and tetrachloroethylene under normal environmental conditions, achieved with biological monitoring, was assessed, and the possible influence of these compounds via drinking water on the body burden was revealed. A total of 79 subjects with no known solvent exposure was selected, by stratified sampling, from the residents of the city of Zagreb. Trichloroethylene and tetrachloroethylene were determined in blood, and trichloroethanol and trichloroacetic acid were determined in plasma and urine. Drinking water samples were also analyzed for trichloroethylene and tetrachloroethylene. Concentrations of trichloroethylene and tetrachloroethylene in blood, trichloroacetic acid in plasma, trichloroacetic acid in urine, trichloroethylene in drinking water, and tetrachloroethylene in drinking water were as follows: < 0.015 to 0.090 micrograms/l, < 0.010 to 0.239 micrograms/l, 8.6 to 148.1 micrograms/l, 1.67 to 102.3 micrograms/24 h, < 0.05 to 22.93 micrograms/l, and 0.21 to 7.80 micrograms/l, respectively. The variation in all results presented is probably a reflection of different environmental contamination with trichloroethylene and tetrachloroethylene in the different city areas. Correlation analyses revealed significant relationships between trichloroethylene and tetrachloroethylene in blood (r = .402, p = .0004); trichloroacetic acid in urine and in plasma (r = .522, p = .0000); and trichloroethylene and tetrachloroethylene in drinking water (r = .800, p = .0000). A division of all parameters into a subgroup (n = 58), taking drinking water concentrations of trichloroethylene above 3 micrograms/l as a basis, demonstrated the same significant relationships as mentioned above.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biological monitoring of occupational exposure to lead with a zinc protoporphyrin (ZPP) meter.

Recent literature dealing with biological monitoring of people exposed to lead at work is reviewed. The widespread trend to regard lower levels of lead in air or in the blood of workers as acceptable or as recommended upper limits is discussed. Based on practical experience over a 6-month period, it is concluded that the zinc protoporphyrin (ZPP) test is an adequate, convenient and inexpensive screening method for monitoring workers exposed to lead in a motor care manufacturing plant.

Environmental Exposure↗

Quality assurance of biological monitoring in view of risk management.

Since recommended occupational exposure limits both for workplace air concentration and biological monitoring results generally have very narrow margin of protection, the probability of the false decision due to measurement error should be perceived and carefully controlled. Japan Federation of Occupational Health Organization has conducted large scale quality control programs since 1987 and reported the results in detail. The meta-analysis of the report of 1992 made it clear that the qualities of the analysis of the leading laboratories as expressed by the coefficient of variation of measurement error are mostly about 5% or less. It was suggested that the warning level should be set at (biological exposure limits minus 2 SD of the measurement error). However, it will not be needed when the SD is less than 2.5% as was found for the analyses of blood lead, urinary hippuric acid, methyl hippuric acid, and mandelic acid by a few best performing laboratories.

Environmental Monitoring↗

Comparison of hair, nails and urine for biological monitoring of low level inorganic mercury exposure in dental workers.

Creatinine-corrected urine mercury measurements in spot urine samples are routinely used in monitoring workers exposed to inorganic mercury. However, mercury measurement in other non-invasive biological material has been used in some epidemiological studies. Dentists and dental nurses remain a group of workers with potential exposure to inorganic mercury through their handling of mercury-containing amalgam, although changes in work practices have reduced the current, likely exposure to mercury. Therefore, dental workers remain an occupational cohort in whom the value of using different biological media to identify exposure to low level inorganic mercury can be investigated. Samples of head hair, pubic hair, fingernails, toenails and urine were analysed for mercury content from a cohort of UK dentists (n=167) and a socioeconomically similar reference population (n=68) in whom any mercury exposure was primarily through diet. The mercury content in all biological material was significantly higher in the dental workers than in the control population (p<0.0001). The geometric mean and 90th percentile mercury concentrations in the urine samples from dentists were 1.7 and 7.3 micromol mol(-1) creatinine, respectively, with only one sample having a value at around the UK's Health and Safety Executive biological monitoring health guidance level of 20 micromol mol(-1) creatinine. Receiver operator characteristic analyses suggested that the ability of the biological material to discriminate between dentists and referents were fingernails>urine approximately equal to toenails>pubic hair approximately equal to head hair. Further investigation is warranted as to why fingernails appear to be such a good discriminator, possibly reflecting some contribution of direct finger contact with amalgam or contaminated surfaces rather than systemic incorporation of mercury into growing nails. Good correlation between head hair and pubic hair mercury levels in all subjects was obtained (r=0.832), which was significantly improved when hair samples weighing <10 mg were excluded (r=0.868). Therefore, under these exposure conditions and using the described pre-analytical washing steps, there is little influence from atmospheric contamination on the level of mercury content of head hair. The choice of non-invasive biological materials for mercury analysis depends on a number of considerations. These include the toxicokinetics of urinary mercury excretion, the growth rates of hair and nail, the nature and time-frame of exposure, and the fact that urine mercury may not reflect the body burden level from dietary methyl mercury. However, the data from this study suggests that urine mercury remains the most practical and sensitive means of monitoring low level occupational exposure to inorganic mercury.

Cohort Studies↗

Biological monitoring of occupational exposure to toxic chemicals. Collection, processing, and storage of specimens.

Exposure to at least 100 different chemicals may be estimated on an individual basis from their concentrations in blood or urine. The present document reviews sources of error in the collection, processing and storage of specimens for this biological monitoring. Physiological factors cause variation in the concentration of chemicals in the body fluids. Distribution of water depends on posture. Exercise and meals cause changes in blood constituents. The urine output varies and, thus, the concentrations of dissolved chemicals change. Many toxic chemicals show short half times in the blood; thus, their concentrations depend on the timing of the specimen collection. Skin absorption may result in dramatically different chemical concentrations in different parts of the circulation. The stability of chemicals in the collected specimens is generally limited: chemical deterioration, adsorption, precipitation, and evaporation are the main causes of losses. For many chemicals, especially for trace elements, contamination of the specimen is the overwhelmingly most important source of error. As the range of the chemicals measured is wide, the relative importance of the sources of error is different for different chemicals. Information on most chemicals is at present very limited. Thus, before commencing a program on biological exposure monitoring, it is advisable to search the optimal conditions for specimen collection, processing, and storage.

Adsorption↗

The effect of respiratory protection with biological monitoring on the health management of lead workers in a storage battery industry.

Respiratory protection with maintenance free respirator and regular biological monitoring with the measurement of zinc protoporphyrin for one year period not only made significant decreases of biological indices indicative of lead exposure (blood lead, delta-aminolevulinic acid in urine) in a storage battery workers, but also reduced the prevalence of lead related symptoms.

Aminolevulinic Acid↗

Biological monitoring of human exposure to atrazine.

Atrazine exposure was evaluated in six manufacturing workers by personal and biological monitoring. Total atrazine exposure varied from 10 to 700 mumol per workshift and total urinary atrazine excretion accounted for 1-2% of the external dose. The spectrum of the urinary atrazine metabolites comprises bi-dealkylated (80%), deisopropylated (10%), deethylated (8%) and unmodified atrazine (2%). The metabolites are eliminated in urine in slightly longer than 24 h: 50% of the amount is excreted in the first 8 h following the workshift.

Adult↗