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PubMedDate not supplied

Strategies for biological monitoring of exposure for contemporary-use pesticides.

Pesticides are used on a massive scale in the United States. The widespread use of these pesticides has made it virtually impossible for the average person to avoid exposure at some level. Generally, it is believed that low-level exposure to these pesticides does not produce acute toxic effects; however, various cancers and other noncancer health endpoints have been associated with chronic exposure to several groups of pesticides. Therefore, it is imperative that well-designed studies investigate the potential relationship between contemporary pesticide exposure and health effects. For these studies to be accurate, reliable methods for determining individual exposure must be used. Biological monitoring is a useful tool for assessing exposure to some contemporary pesticides. As with any analytical method, biological monitoring entails many difficulties, but, in many instances, they can be overcome by the logical use of available information and information acquired in carefully designed studies. At the Centers for Disease Control and Prevention (CDC), we have acquired extensive experience in the development and application of specific techniques for biological monitoring of a variety of toxicants, including many of the contemporary-use pesticides. We have used these methods to measure the internal dose of pesticides received by people in acute and chronic incidents resulting from both environmental and industrial exposure. Additionally, we have established normative values, or reference ranges, of several pesticides based on measurements of their metabolites in the urine of randomly selected adults in the US population. These data have been successfully used to distinguish overt exposures from 'background' exposure. In this paper, we present several examples of the usefulness of biological monitoring in urine and blood and describe the difficulties involved with developing methods in these matrices. We also present a general strategy, considerations, and recommendations for developing biological monitoring techniques for measuring the internal dose of contemporary-use pesticides.

Adult↗

PubMedDate not supplied

[Biological monitoring and risk assessment].

Risk assessment in occupational medicine is the part of risk analysis where physicians also contribute. A risk is the probability of an adverse health effect and derives from the hazard posed by a given chemical and from exposure characteristics. Due to the complexity of this process, models are used in occupational medicine, where risk factors are identified and exposure estimated, combined with an understanding of the severity of possible effects. Theoretically, the advantages of biological monitoring are obvious. However, the paucity of available data on biological monitoring limits its uses. Moreover, the utilization of data on biological monitoring requires evaluation of their significance. Examples are discussed to highlight advantages and limitations of biological monitoring data in both hazard and risk assessments. They include exposure to polycyclic aromatic hydrocarbons, benzene, other carcinogens, paraquat and polychlorinated biphenyls.

Benzene↗

PubMed1986

[Biological monitoring at the work site].

Exposure to industrial chemicals is assessed by ambient monitoring (external exposure/dose), by health surveillance (detection of adverse biological/health effects in exposed workers) and by biological monitoring (evaluation of the internal exposure of the organism to a chemical agent). Objectives, principal advantages and limitations of biological monitoring are discussed; the programs of biological monitoring as a part of the health surveillance of Swiss workers guided by the Swiss National Accident Insurance Fund are briefly summarized.

Air Pollutants, Occupational↗

PubMed1990

Environmental and biological monitoring for lead exposure in California workplaces.

Patterns of environmental and biological monitoring for lead exposure were surveyed in lead-using industries in California. Employer self-reporting indicates a large proportion of potentially lead-exposed workers have never participated in a monitoring program. Only 2.6 percent of facilities have done environmental monitoring for lead, and only 1.4 percent have routine biological monitoring programs. Monitoring practices vary by size of facility, with higher proportions in industries in which larger facilities predominate. Almost 80 percent of battery manufacturing employees work in job classifications which have been monitored, versus only 1 percent of radiator-repair workers. These findings suggest that laboratory-based surveillance for occupational lead poisoning may seriously underestimate the true number of lead poisoned workers and raise serious questions regarding compliance with key elements of the OSHA Lead Standard.

California↗

PubMed1995

Interlaboratory quality control and status of n-hexane biological monitoring in Japan.

This paper reports the problem of interlaboratory quality control and the actual condition of biological monitoring of n-hexane among the seven major laboratories specializing in clinical chemistry tests, where more than 80% of the total urine specimens in Japan have been analyzed after the beginning of biological monitoring of n-hexane in 1989. First, transportation conditions of urine specimens and transportation effects on measurement results were studied. The seven major laboratories carried urine specimens at distances of more than 450 km from the University of Occupational and Environmental Health (UOEH) to the respective laboratories and had at least one transit terminal where specimens from various areas were collected and transferred to the analytical laboratories. All laboratories used cooler boxes with dry ice or ice bars and stored the specimens in freezers or refrigerators. Specimens arrived at the final destinations within 24 hours. The transportation from institutes for health examination to the laboratories did not affect the measurement results of 2,5-hexanedione (HD), a determinant of n-hexane biological monitoring. Interlaboratory cross-checks were performed among the seven major laboratories and four institutes for occupational health examination that have their own analytical laboratories. All of the laboratories analyzed HD by acid hydrolysis (pH < 1.0); interlaboratory differences were recognized at the first cross-check. After some laboratories intensified gas chromatography (GC) maintenance and changed to a new column, the interlaboratory variation lessened.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Monitoring↗

PubMed1993

Designing a biological monitoring program to assess community exposure to chromium: conclusions of an expert panel.

The possible benefits of biological monitoring of large groups of people potentially exposed to environmental contaminants has become an area of much interest in recent years. Because chromite-ore processing residue has been found in some soils in northern New Jersey, urinary chromium monitoring of people in the community was evaluated as a potentially useful tool. In an attempt to identify those who could be exposed and to quantify the magnitude of exposure to the chromium in these soils, the New Jersey Department of Health (NJDOH) initiated a public health screening project. In 1992, the NJDOH proposed to evaluate over 4000 people who lived or worked near these sites. Volunteers were administered a questionnaire and were given a limited physical examination, and a single spot urine sample was collected. Because of the difficulties in using urinary chromium to assess low-level exposure and the potential implications of any regulatory decisions that could be based on the results of this project, a panel of experts was convened to evaluate the protocol. The panel consisted of five scientists and physicians with expertise in toxicology, dermatology, epidemiology, biological monitoring, and analytical chemistry. Like a World Health Organization group, the panel concluded that although urine biomonitoring can be useful in evaluating high levels of exposure to chromium, it is not reliable for assessing low-level exposure similar to that which may have occurred in northern New Jersey. The panel also noted that when urinary biomonitoring is to be used to assess the public's possible exposure, a large number of precautions must be taken to ensure the accuracy and usefulness of the results. The single most important recommendation was to collect a second, and perhaps a third, spot urine (or 24-h urine) sample before concluding that a person may be routinely overexposed. These suggestions are applicable to designing a biomonitoring program for nearly any environmental contaminant to which a community may be exposed. A review of scientific literature associated with biological monitoring of chromium is provided.

Absorption↗

PubMed1994

Biological monitoring of exposure to 3-chloro-4-fluoroaniline by determination of a urinary metabolite and a hemoglobin adduct.

In two studies, involving 75 and 72 workers, potential exposure to 3-chloro-4-fluoroaniline (CFA) was biologically monitored by determination of its main urinary metabolite 2-amino-4-chloro-5-fluorophenol sulfate (CFA-S). As this method only allows the detection of recent exposure, analysis of CFA adducts bound to hemoglobin (Hb) was investigated as a method that allows biological monitoring of exposure to CFA over longer periods. The median CFA-S concentration in 67 samples from the first study was 0.14 mumole/g creatinine (range < 0.05-2.82) and in 201 samples from the second study 0.21 mumole/g creatinine (range < 0.05-6.05). In addition, urine samples, collected after shifts with supposed incidental exposure, slightly higher concentrations were measured: 0.27 mumole/g creatinine (range < 0.05-122; 18 samples) and 0.76 mumole/g creatinine (range < 0.05-18.5; 46 samples), respectively. The median Hb adduct concentration in 75 samples from the first study was 9 pmoles CFA/g Hb (range < 5-640) and in 46 samples from the second study 12 pmoles/g Hb (range 3-24). In 24 blood samples collected after incidents, a median concentration of 13 pmoles CFA/g Hb (range < 5-52) was found. Urinary CFA-S and Hb adducts correlated well in samples collected shortly after incidental exposures. However, in 25% of the operators, no CFA-S was detected during routine biological monitoring while Hb adduct analysis showed clear evidence of exposure. This indicates that because of the stability of Hb adducts of CFA in blood, intermittent exposure to CFA is more reliably biologically monitored by determination of Hb adducts of CFA than by assessment of urinary CFA-S.

Aniline Compounds↗

PubMed2005

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.

Biomarkers↗

PubMed1999

[Biological monitoring of occupational exposure in welders of stainless steel. Immunologic methods].

Biological monitoring of occupational exposure to toxic compounds enables an early detection of adverse health effects. Apart from the standard biological monitoring methods of occupational exposure represented by metabolites and enzymes activities analysis also immunological detection methods seem to be promising. The changes of immunological system are demonstrable extraordinary sensitive markers of load of organism. The process of welding belongs between important sources of pollution of working environment with heavy metals and other harmful compounds including polycyclic aromatic hydrocarbons. According to IARC classification the welding fumes are included into group 2B and are supposed as possible human carcinogens. Numbers of different epidemiological studies have proved relationship between welding and serious health disorders namely malignancies. We recorded a number of changes in immunological parameters when compared with those in control group in our study. The results of analysis were statistically evaluated. The statistically significant reduction of number of phagocytosis capable cells was found in the group of welders when compared with the control group. The levels of neopterin, beta-2-microglobulin and IL-1 beta have indirectly monitored cell component of immunological response. In the case of these markers a statistically significant increases were found in the group of welders. We found statistically significant IgM decrease and statistically significant IgA increase in humoral responses with the same group when compared with control group.

Adult↗

PubMed1983

Liquid chromatography of urinary porphyrins for the biological monitoring of occupational exposure to porphyrinogenic substances.

Very sensitive and precise analytical methods for measuring total porphyrin excretion and the relative amounts of different porphyrins in urine are required in order to monitor the biological effects of porphyrinogenic substances in workers and the general population. Many analytical steps of a HPLC method for measuring porphyrins as methyl esters in urine have been perfected. Sensitivity is 0.1 microgram/1 for each type of porphyrin, and average recovery is 92% in the range of 50-450 micrograms/liter porphyrins. The coefficient of variation is 3.4% within a series and 12.5% between series. Chemical oxidation before analysis and appropriate storing of the samples are the key points in achieving high quality results. The urinary excretion of porphyrins in healthy male workers varies within the range 21 to 161 micrograms/liter (95% limits of a group of 78 subjects). Concomitant factors, like drug use or liver disorders, were found to alter urinary porphyrin excretion. The proposed method permits the detection of extremely small alterations in porphyrin excretion resulting from occupational exposure to industrial chemicals such as, for example, mild coproporphyrinuria or early stages of chemical porphyria induced by polyhalogenated arylhydrocarbons.

Adult↗

PubMed2000

Biological monitoring of occupational exposure to N,N-dimethylformamide--the effects of co-exposure to toluene or dermal exposure.

OBJECTIVES: The objective of this study is to assess the exposure and intake dose of N,N-dimethylformamide (DMF) and the correlation between them, according to the type of exposure for the workers in the DMF industry. METHODS: We monitored 345 workers occupationally exposed to DMF, from 15 workshops in the synthetic fiber, fiber coating, synthetic leather and paint manufacturing industries. Ambient monitoring was carried out with personal samplers to monitor the external exposure. Biological monitoring was done to determine the internal dose by analyzing N-methylformamide (NMF) in end-shift urine. Work procedure and exposure type of each DMF workshop was carefully surveyed, to classify workers by exposure type according to work details. Workers were classified into three groups (Group A: continuous and direct exposure through inhalation and skin; Group B: intermittent and short-term exposure through inhalation and skin; Group C: continuous and indirect exposure mostly through inhalation). RESULTS: Geometric mean of DMF concentration in air was 2.62 (GSD 5.30) ppm and that of NMF in urine was 14.50 (GSD 3.89) mg/l. In the case of continuous absorption through inhalation and dermal exposure (Group A), the value of NMF in urine corresponding to 10 ppm of DMF was 45.3 mg/l (r = 0.524, n = 178), 39.1 mg/g creatinine (r = 0.424), while it was 37.7 mg/l (r = 0.788, n = 37), 24.2 mg/g creatinine (r = 0.743) in the case of absorption mostly through inhalation (Group C). Creatinine correction reduced the correlation between two parameters. CONCLUSION: The NMF in urine corresponding to 10 ppm DMF, of the dermal and inhalation exposure group was 39.1 mg/g creatinine (r = 0.424, n = 178), while that of the inhalation exposure-only group was 24.2 mg/g creatinine (r = 0.743, n = 37). Co-exposure with toluene reduced the NMF excretion in urine.

Air Pollutants↗

PubMed1997

The urinary excretion of solvents and gases for the biological monitoring of occupational exposure: a review.

'In the field' application of the measurement of urinary excretion of unmodified solvent for the biological monitoring of exposed workers has been investigated in many recent papers. The results obtained for several solvents are reviewed. The values of correlation coefficients (r) and regression lines obtained for benzene, toluene, xylene, styrene, n-hexane, cyclohexane, 2- and 3-methylpentane, methyl chloride, tetrachloroethylene, carbon tetrachloride, methyl chloroform, p-dichlorobenzene, nitrous oxide, halothane, isoflurane, enflurane, acetone, methyl ethyl ketone and methyl isobutyl ketone are presented. The correlations observed were generally good: r values range from 0.50-0.97, and the majority are between 0.84 and 0.90. The regression lines reported for the same solvent in different studies present some variability: this is possibly due to an inadequate control of factors influencing the relationship between external dose and absorption, such as differences in body burden, work load, individual characteristics, etc. These factors are discussed. As a whole, results reported in the literature show that measuring of urinary excretion of unmodified solvents provides a highly sensitive and specific exposure index, and can also be applied for the biological monitoring of occupational exposure to low levels of solvents or to solvent mixtures. Nevertheless, for an adequate assessment of biological limit values, further studies evaluating the reproducibility of regression lines are needed, given that the aspects influencing the correlation between external dose and urinary excretion are fully controlled. Another crucial aspect is the correlation with early effects: even though this has yet to be evaluated for several solvents, for others such as styrene and perchloroethylene a good correlation was obtained, further supporting the usefulness of the measurement of urinary excretion of solvent for the biological monitoring of occupational exposure.

Absorption↗

PubMed1999

The role of biological monitoring in the health management of lead-exposed workers.

In 1967, the problem of occupational lead exposure came to public attention in Korea. Since then, regular progress has been made in lowering workplace lead exposures, instituting new workplace controls, and implementing health examinations of exposed workers. Serious lead poisoning episodes led to the introduction of biological monitoring programs on a voluntary basis in high lead exposure facilities in Korea. Occupational health services for lead workers in Korea during the last 10 years could be categorized into three phases. During the first phase (1988-1993), effort was directed at increasing awareness among workers concerning the hazards of lead exposure, biological monitoring was commenced with zinc protoporphyrin (ZPP), and a respiratory protection program was introduced. During the second phase (1994-1996), a computerized health management system of lead workers was developed, blood lead measurement was added for biological monitoring, and engineering controls were introduced in the workplace to lower air lead levels to comply with air lead regulations. Finally, during the third phase (1997-present), bone lead measurement by X-ray fluorescence was introduced to evaluate total body lead burden. During the period 1988-1998, air lead levels have remained generally steady and above the permissible exposure level (PEL), but ZPP and blood lead levels have shown a steady decline. It was discovered that in a developing country like Korea, which cannot introduce engineering controls quickly to protect lead workers, biological monitoring was very useful in identifying and lowering excess lead absorption. In the future, as average exposure duration continues to rise, bone lead measurement may be recommended to adequately protect the long-term health of lead workers.

Air Pollutants, Occupational↗

PubMed1998

[Biologic monitoring of the health status of workers exposed to lead].

Use of biologic monitoring for workers exposed to lead is the most efficient means preventing lead intoxication all over the world. Considering WHO recommendations and personal research, the authors specified national system of biologic monitoring for workers exposed to lead. The system covers mandatory control of serum and urinary lead levels. The authors based biologic MAC for lead in serum-50 mg/dl (males) and 30 mg/dl (females).

Adolescent↗

PubMed1986

Health surveillance and biological monitoring of pesticide formulators in India.

Results of health survey and biological monitoring in pesticide formulators exposed to a combination of pesticides, an organophosphorus (OP) insecticide (phorate) and a persistent chlorinated insecticide (technical hexachlorocyclohexane; HCH; BHC) are reported. Exposure of 160 workers to a combination of pesticides (malathion, parathion, DDT and HCH) resulted in 73% of the workers showing toxic signs and symptoms. Formulators showed marked inhibition of whole blood, plasma and red blood cell cholinesterase (ChE) activity and slightly higher concentrations of DDT and HCH in serum. An interesting observation was that over 25% of the formulators showed ECG aberrations. The ECG changes were not related to whole blood ChE activity. Exposure to the chlorinated insecticide HCH in 19 workers engaged in the manufacture of technical HCH resulted in toxic signs and symptoms in over 90% of the subjects. The HCH concentrations in serum showed a ten-fold increase. Changes in the liver enzymes ornithine carbamyl transferase (OCT), gamma-glutamyl transpeptidase (GGTP), leucine aminopeptidase (LAP) and in immunoglobulin M(IgM) showed possible effects on liver and humoral immunity. ECG monitoring showed evidence of cardiac effects. Exposure of 40 formulators to a highly toxic OP insecticide (phorate) showed that over 60% of the workers suffered from toxic effects in spite of using a complete set of protective clothing. A marked and progressive inhibition in whole blood and plasma ChE activity was found during the two weeks of exposure to phorate. An appreciable recovery in ChE activity was observed 10 days after cessation of exposure. These surveys have established the need to practice and develop biological monitoring techniques to assess exposure and predict health risks in workers occupationally exposed to pesticides.

Adolescent↗

PubMed1993

Biological monitoring for pesticide exposure--the role of human volunteer studies.

Predictions of human pesticide metabolism which are needed for the interpretation of biological monitoring data are frequently made from animal studies. Consequently, assumptions have to be made about the relationship between absorbed dose and metabolite excretion. The results from two human volunteer studies highlight the problems associated with extrapolating from animal studies in this way. The pyrethroid insecticide cypermethrin shows markedly different metabolite patterns when administered orally or dermally in man. Following dermal dosing the ratio of trans/cis cyclopropane acids is approximately 1:1, compared to 2:1 after oral administration. The ratio of total cyclopropane acids to phenoxybenzoic acids also differs depending on the route (dermal 1:4, oral 1:0.8). A knowledge of human metabolism by these two routes enables a much more meaningful interpretation of biological monitoring measurements. The herbicide molinate forms a mercapturate conjugate as a major urinary metabolite in the rat (35%). In volunteers at low dose levels this metabolite is present at insignificant levels (< 1%) and 4-hydroxymolinate is a much more abundant metabolite (39%). This shows that extrapolation between species can be very misleading. It is concluded that the benefits of using human volunteers for metabolism studies at low doses far outweigh the minimal risks involved. As a basis for biological monitoring such studies can lead to a greatly improved risk assessment for pesticides in use.

Administration, Cutaneous↗

PubMedDate not supplied

A human exposure study to investigate biological monitoring methods for 2-butoxyethanol.

2-Butoxyethanol is a glycol ether widely used in printing inks, varnishes and cleaning fluids. As skin absorption can be significant, biological monitoring is useful in monitoring worker exposure. A number of analytes and matrices have been used previously, including 2-butoxyethanol in blood and free and total 2-butoxyacetic acid in urine. Using a combination of a volunteer study and samples from exposed workers, we compared the applicability of some of the biological monitoring markers available. We conclude that 2-butoxyethanol in blood is not a suitable marker for biological monitoring due to sampling problems. In view of the low-level exposures reported in occupational surveys, 2-butoxyethanol in breath is also unsuitable because of a lack of sensitivity. Measuring 2-butoxyacetic acid in blood is possible, although non-invasive urine samples are preferred. Free 2-butoxyacetic acid in urine has previously been widely used; however, we found that the extent of conjugation of 2-butoxyacetic acid in urine varied from 0 to 100% both within and between individuals and is not related to time, concentration or urine pH. Data from 48 exposed workers suggested that an estimated 57% (95% confidence interval 44-70%) of the total 2-butoxyacetic acid is excreted in the conjugated form, and that conjugation may be activated above a certain exposure level. Using total 2-butoxyacetic acid significantly reduced inter-individual variation. Elimination half-lives for free and total 2-butoxyacetic acid were similar ( approximately 6 h) and there was no delay in excretion of the conjugated metabolite (peak excretion for both free and total was between 6 and 12 h after the end of exposure). In conclusion, we propose that total butoxyacetic acid (after acid hydrolysis) in urine is the biomarker of choice for monitoring exposure to 2-butoxyethanol. Urine samples should be collected post-shift towards the end of the working week.

Adult↗

PubMed1984

Biological monitoring of workers exposed to 4,4'-methylenebis (2-chloroaniline) (MBOCA).

A biological monitoring programme has been developed for assessing occupational exposure to 4,4'-methylenebis (2-chloroaniline) (MBOCA) in a factory which manufactures polyurethane elastomers. In a systematic programme of biological monitoring over a five year period urinary MBOCA concentrations have been used to provide evidence of absorption of MBOCA. Improvements in the handling and use of MBOCA have coincided with a steady reduction in the urinary MBOCA concentrations.

Benzhydryl Compounds↗