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PubMed2000

Benchmark concentrations for methylmercury obtained from the Seychelles Child Development Study.

Methylmercury is a neurotoxin at high exposures, and the developing fetus is particularly susceptible. Because exposure to methylmercury is primarily through fish, concern has been expressed that the consumption of fish by pregnant women could adversely affect their fetuses. The reference dose for methylmercury established by the U.S. Environmental Protection Agency was based on a benchmark analysis of data from a poisoning episode in Iraq in which mothers consumed seed grain treated with methylmercury during pregnancy. However, exposures in this study were short term and at much higher levels than those that result from fish consumption. In contrast, the Agency for Toxic Substances and Disease Registry (ATSDR) based its proposed minimal risk level on a no-observed-adverse-effect level (NOAEL) derived from neurologic testing of children in the Seychelles Islands, where fish is an important dietary staple. Because no adverse effects from mercury were seen in the Seychelles study, the ATSDR considered the mean exposure in the study to be a NOAEL. However, a mean exposure may not be a good indicator of a no-effect exposure level. To provide an alternative basis for deriving an appropriate human exposure level from the Seychelles study, we conducted a benchmark analysis on these data. Our analysis included responses from batteries of neurologic tests applied to children at 6, 19, 29, and 66 months of age. We also analyzed developmental milestones (age first walked and first talked). We explored a number of dose-response models, sets of covariates to include in the models, and definitions of background response. Our analysis also involved modeling responses expressed as both continuous and quantal data. The most reliable analyses were considered to be represented by 144 calculated lower statistical bounds on the benchmark dose (BMDLs; the lower statistical bound on maternal mercury hair level corresponding to an increase of 0.1 in the probability of an adverse response) derived from the modeling of continuous responses. The average value of the BMDL in these 144 analyses was 25 ppm mercury in maternal hair, with a range of 19 to 30 ppm.

Animals↗

PubMed2005

Biological monitoring of experimental human exposure to hydrocarbon solvent mixtures.

The aim of the study was to develop and to validate a suitable analytical method in order to assess the internal exposure of persons to commercial products of hydrocarbon solvent mixtures (HSM). Twenty healthy volunteers were exposed to vapours of five commercial HSM for 8h at 200-1,000 mg/m(3) air. Aromatic-rich, aromatic-poor and aromatic-free HSM were used, as well as isohexane and technical hexane mixtures. A total of 300 exposures were carried out at rest or with an exercise period of 10 min/h at 50 and 75 W. Blood samples for the determination of the HSM were collected before and immediately after exposure. They were analyzed with a headspace analyzer by gas chromatography and mass spectrometry. The analytical method has detection limits of 2-50 microg HSM/L blood. With this method we obtained intra- and interassay variation coefficients of 3.7-15.1%, at concentrations of 53-1,500 microg HSM/L blood. The mean values of the HSM of the 20 volunteers after 8h range between 89 mug/L (technical hexane-mixture) and 1,369 microg/L blood (aromatic-free HSM) at rest. Physical exercises of 50 and 75 W, respectively, lead to a significant increase of the blood-concentrations by mean factors between 1.2 and 1.9 for the five HSM. In conclusion, our results demonstrate that physical activity should be considered in the setting of occupational exposure limits.

Adult↗

PubMed2001

Fluorescence fluctuation analysis for the study of interactions between oligonucleotides and polycationic polymers.

The interactions between a cationic polymer, poly(2-dimethylamino)ethyl methacrylate (pDMAEMA), and negatively charged rhodamine-labeled 25-mer phosphodiester oligonucleotides (Rh-ONs) were studied by fluorescence fluctuation spectroscopy and other techniques. The composition of the pDMAEMA/Rh-ON complexes was investigated as a function of the charge ratio (+/-) by increasing the pDMAEMA concentration and keeping the Rh-ON concentration constant. We applied two different methods for analyzing the fluorescence fluctuation profiles of the pDMAEMA/Rh-ON complexes, which depended on their composition. First, we analyzed the data with the photon counting histogram (PCH) technique, which determines the molecular brightness and the concentration of fluorophores (Chen et al, 1999). A particular challenge for the data analysis is the occurrence of sudden fluorescence bursts in the fluorescence fluctuation profiles, which are linked to the appearance of multimolecular complexes (i. e. when several Rh-ONs were present in one complex). A quantitative interpretation of the analysis for the complexes remains challenging and is connected to the rarity of the fluorescent bursts, which do not provide sufficient data statistics. To specifically address the problem of the fluorescent bursts we employed a method described by Van Craenenbroeck et al. (1999). This method, applicable only when data were integrated over much longer time bins, allowed us to estimate the number of fluorescence bursts which could be considered as a relative measure of the amount of multimolecular complexes present. When monomolecular complexes were formed, i. e. at high values of the charge ratio, highly intense fluorescence peaks were not present and the interpretation of the PCH analysis was more straightforward. The molecular brightness of the species (epsilon), as revealed from PCH analysis, was greater than epsilon for the free Rh-ONs, indicating that the Rh-ONs were attached to pDMAEMA chains.

Cations↗

PubMedDate not supplied

[Integration of biological and workplace monitoring as an efficient control of chemical exposure].

Evaluation of professional exposure by means of biological monitoring is nowadays a consolidated method in the practice of Occupational Health. Generally biological monitoring is used simultaneously to ambient monitoring as a complementary method to obtain a mutual validation of exposure assessment. Experience gathered in the last years allowed us to verify that at low exposure levels, the values of biological indicators of dose are always markedly below their limits. Consequently, under standard conditions, it appears useful to alternate the two different exposure assessments (either biological or ambient monitoring), in order to obtain an efficient control of chemical exposure. Moreover, this methodological approach allows a better integration of all the professionals, who manage directly or indirectly the activities concerning Occupational Health and Industrial Hygiene, having as their first goal the health protection of employees and job environment.

Air Pollutants, Occupational↗

PubMed2005

Acute effects of an organic solvent mixture on the human central nervous system.

OBJECTIVES: At workplaces, organic solvents are often used as mixtures. Nevertheless, there is limited knowledge of their acute effects on human central nervous system. Here we report the effects of a toluene-acetone mixture. METHODS: In a parallel design, subgroups of 12 healthy men each were exposed to a mixture containing 25 ppm acetone and 250 ppm toluene or to air (control) in an exposure chamber for 4.5 hours. Concentrations corresponded to the German TLV (TRGS 403). Concentrations of toluene and acetone in venous blood were measured by headspace gas chromatography. Subjects were sedentary. The following tests were performed before and at the end of exposure: Questionnaires, simple reaction time, vigilance, quantitative analysis of EEG with open and closed eyes and during the Color Word Stress test, and visual evoked potentials (VEP). RESULTS: Blood levels were 0.14 (+/- 0.04 SD) mg toluene/l and 5.43 (+/- 1.37 SD) mg acetone/l at the end of solvent exposure. Scores of neurotoxic and irritating symptoms were not elevated during solvent exposure. Exposed subjects performed as well as control subjects on the simple reaction time test and on the vigilance test, neither reaction time nor number of hits differed significantly. A general linear model on log transformed spectral power values showed insignificant changes in EEG. In the alpha subset2-band an average reduction to 86 % was observed in exposed as compared to non exposed subjects with closed eyes, a reduction to 88 % in the theta-band with open eyes, and a reduction to 92 % in the theta-band during the Color Word Stress test. VEP P 100 latencies and amplitudes did not change. CONCLUSION: The mixture consisting of toluene and acetone did not cause any adverse acute effect. With respect to EEG data, possible subclinical effects on central nervous system cannot be excluded.

Acetone↗

PubMed2003

Spatial distribution of heavy metals in urban soils of Naples city (Italy).

Concentrations of surface and sub-surface soil Cu, Cr, Pb and Zn in the Naples city urban area were measured in 1999. Contourmaps were constructed to describe the metals spatial distribution. In the most contaminated soil samples, metals were speciated by means of the European Commission sequential extraction procedure. At twelve sites, Cu, Pb and Zn levels in soil were compared with those from a 1974 sampling. Many surface soils from the urban area as well as from the eastern industrial district contained levels of Cu, Pb and Zn that largely exceeded the limits (120, 100 and 150 mg kg(-l) for Cu, Pb and Zn, respectively) set for soils of public, residential and private areas by the Italian Ministry of Environment. Chromium values were never above regulatory limits(120 mg kg(-1)). Copper apparently accumulates in soils contiguous to railway lines and tramway. Cu and Cr existed in soil mainly inorganic forms (-68%), whereas Pb occurs essentially as residual mineral phases (77%). The considerable presence of Zn in the soluble, exchangeable and carbonate bound fraction (23%) suggests this element has high potential bioavailability and leachability through the soil. Concentrations of Cu, Pb and Zn have greatly increased since the 1974 sampling, with higher accumulation in soils from roadside fields.

Chemical Fractionation↗

PubMed2006

Rating exposure control using Bayesian decision analysis.

A model is presented for applying Bayesian statistical techniques to the problem of determining, from the usual limited number of exposure measurements, whether the exposure profile for a similar exposure group can be considered a Category 0, 1, 2, 3, or 4 exposure. The categories were adapted from the AIHA exposure category scheme and refer to (0) negligible or trivial exposure (i.e., the true X 0.95 < or =1%OEL), (1) highly controlled (i.e., X 0.95 < or =10%OEL), (2) well controlled (i.e., X 0.95 < or =50%OEL), (3) controlled (i.e., X 0.95 < or =100%OEL), or (4) poorly controlled (i.e., X0.95 > or =1%OEL) exposures. Unlike conventional statistical methods applied to exposure data, Bayesian statistical techniques can be adapted to explicitly take into account professional judgment or other sources of information. The analysis output consists of a distribution (i.e., set) of decision probabilities: e.g., 1%, 80%, 12%, 5%, and 2% probability that the exposure profile is a Category 0, 1, 2, 3, or 4 exposure. By inspection of these decision probabilities, rather than the often difficult to interpret point estimates (e.g., the sample 95th percentile exposure) and confidence intervals, a risk manager can be better positioned to arrive at an effective (i.e., correct) and efficient decision. Bayesian decision methods are based on the concepts of prior, likelihood, and posterior distributions of decision probabilities. The prior decision distribution represents what an industrial hygienist knows about this type of operation, using professional judgment; company, industry, or trade organization experience; historical or surrogate exposure data; or exposure modeling predictions. The likelihood decision distribution represents the decision probabilities based on an analysis of only the current data. The posterior decision distribution is derived by mathematically combining the functions underlying the prior and likelihood decision distributions, and represents the final decision probabilities. Advantages of Bayesian decision analysis include: (a) decision probabilities are easier to understand by risk managers and employees; (b) prior data, professional judgment, or modeling information can be objectively incorporated into the decision-making process; (c) decisions can be made with greater certainty; (d) the decision analysis can be constrained to a more realistic "parameter space" (i.e., the range of plausible values for the true geometric mean and geometric standard deviation); and (e) fewer measurements are necessary whenever the prior distribution is well defined and the process is fairly stable. Furthermore, Bayesian decision analysis provides an obvious feedback mechanism that can be used by an industrial hygienist to improve professional judgment. For example, if the likelihood decision distribution is inconsistent with the prior decision distribution then it is likely that either a significant process change has occurred or the industrial hygienist's initial judgment was incorrect. In either case, the industrial hygienist should readjust his judgment regarding this operation.

Bayes Theorem↗

PubMed2001

Proposed occupational exposure limits for select ethylene glycol ethers using PBPK models and Monte Carlo simulations.

Methoxyethanol (ethylene glycol monomethyl ether, EGME), ethoxyethanol (ethylene glycol monoethyl ether, EGEE), and ethoxyethyl acetate (ethylene glycol monoethyl ether acetate, EGEEA) are all developmental toxicants in laboratory animals. Due to the imprecise nature of the exposure data in epidemiology studies of these chemicals, we relied on human and animal pharmacokinetic data, as well as animal toxicity data, to derive 3 occupational exposure limits (OELs). Physiologically based pharmacokinetic (PBPK) models for EGME, EGEE, and EGEEA in pregnant rats and humans have been developed (M. L. Gargas et al., 2000, Toxicol. Appl. Pharmacol. 165, 53-62; M. L. Gargas et al., 2000, Toxicol. Appl. Pharmacol. 165, 63-73). These models were used to calculate estimated human-equivalent no adverse effect levels (NAELs), based upon internal concentrations in rats exposed to no observed effect levels (NOELs) for developmental toxicity. Estimated NAEL values of 25 ppm for EGEEA and EGEE and 12 ppm for EGME were derived using average values for physiological, thermodynamic, and metabolic parameters in the PBPK model. The uncertainties in the point estimates for the NOELs and NAELs were estimated from the distribution of internal dose estimates obtained by varying key parameter values over expected ranges and probability distributions. Key parameters were identified through sensitivity analysis. Distributions of the values of these parameters were sampled using Monte Carlo techniques and appropriate dose metrics calculated for 1600 parameter sets. The 95th percentile values were used to calculate interindividual pharmacokinetic uncertainty factors (UFs) to account for variability among humans (UF(h,pk)). These values of 1.8 for EGEEA/EGEE and 1.7 for EGME are less than the default value of 3 for this area of uncertainty. The estimated human equivalent NAELs were divided by UF(h,pk) and the default UFs for pharmacodynamic variability among animals and among humans to calculate the proposed OELs. This methodology indicates that OELs (8-h time-weighted average) that should protect workers from the most sensitive adverse effects of these chemicals are 2 ppm EGEEA and EGEE (11 mg/m(3) EGEEA, 7 mg/m(3) EGEE) and 0.9 ppm (3 mg/m(3)) EGME. These recommendations assume that dermal exposure will be minimal or nonexistent.

Administration, Inhalation↗

PubMed2005

Ototoxic occupational exposures for a stock car racing team: I. Noise surveys.

The National Institute for Occupational Safety and Health (NIOSH) surveyed noise exposure for a professional stock car team at their race shop and during two races at one racetrack. At the team's shop, area sound pressure levels (SPLs) were measured for various work tasks. Equivalent levels (Leqs) ranged from 58 to 104 decibels, A-weighted (dBA). Personal noise dosimetry was conducted for at least one employee for each job description in race car assembly (n = 9). The Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) of 90 dBA for an 8-hour, 5-dB exchange rate time-weighted average (TWA) was never exceeded, but in two instances values exceeded OSHA's action level of 85 dBA for hearing conservation implementation. The NIOSH recommended exposure limit (REL) of 85 dBA for a 3-dB exchange rate Leq was exceeded for five of the measured jobs. During the races, SPLs averaged above 100 dBA in the pit area where cars undergo adjustments/refueling, both before and during the race. Peak levels reached 140 dB SPL. NIOSH REL was exceeded for every personal noise dosimetry measurement. Recommendations for hearing protection and communication are presented.

Automobiles↗

PubMed2002

An examination of the physical properties, fate, ecotoxicity and potential environmental risks for a series of propylene glycol ethers.

Propylene glycol ethers (PGEs) are comprised of mono-, di- and tri-PGEs and several of their acetate esters. The nature of the range of applications that use PGEs suggests that there is a potential for both intentional and unintentional entry of the materials into the environment. Selected physical/chemical properties, fate characteristics, aquatic toxicity data and calculated environmental concentrations were used to assess potential risks from the manufacture, handling, use, and disposal of PGEs. In general, the PGEs are low to moderately volatile, have high aqueous solubilities, low octanol-water partition coefficients (Kow), and bioconcentration factor values of <10, which indicate they are unlikely to accumulate in aquatic food chains. Both abiotic and biological degradation processes reduce environmental concentrations of PGEs. In air, vapor-phase PGEs react with photo-chemically produced hydroxyl radicals and have half-lives ranging from 5.5 to 34.4 h. A variety of ready and inherent biodegradation test methods, as well as tests that simulate biodegradation in wastewater treatment plants, surface water and soil have been conducted on PGEs. Significant aerobic biodegradation was generally observed, with a range of biodegradation half-lives on the order of 5-25 d. Acute aquatic toxicity studies with PGEs resulted in LC50 values ranging from approximately >100 to >20,000 mg/l for freshwater fish, the pelagic invertebrate Daphnia magna, green algae Selenastrum capricornutum (now called Pseudokirchneriella capricornutum) and bacteria. Level 3 multi-media modeling (EQC model of Mackay) was used to simulate regional-scale concentrations of PGEs in air, soil, water, and sediment. Toxicity thresholds were then compared with regional-scale water, soil and sediment concentrations to determine hazard quotients. Based upon this analysis, concentrations of PGEs are unlikely to pose adverse risks to the environment.

Animals↗

PubMed2003

Indirect mechanisms of genotoxicity.

Indirect mechanisms of genotoxicity correspond to interactions of mutagens with non-DNA targets, and are expected to show threshold concentration-effect response curves. If these thresholds can be proven experimentally they may provide a third alternative for risk assessment, besides the No Effect Level/Safety Factor approach and the low dose linear extrapolation method. We contributed significantly to the in vitro assessment of thresholds in human lymphocytes exposed to the spindle inhibitors nocodazole and carbendazim showing dose dependency and existence of lower thresholds for induction of non-disjunction as compared to chromosome loss. Micronuclei correlated with p53-independent or p53-dependent apoptosis and elimination of aneuploid cells. Extrapolation from in vitro threshold values to the in vivo situation remains unsolved. Comparing the in vitro threshold values for griseofulvin in human and rat lymphocytes with in vivo NOAEL/LOAEL in bone marrow/gut/erythrocytes suggests that the in vitro human system is the most sensitive. The threshold for induction of non-disjunction in in vitro maturing, nocodazole-exposed mouse oocytes was in the same low range. Regulators (UK Committee on Mutagenicity, http://www.doh.gov.uk/com/com.htm) considered the importance of thresholds for indirect mechanisms of genotoxicity. Acceptance of a non-linear extrapolation for mutagens requires mechanistic studies identifying the mutagen/target interactions. Moreover appropriate risk evaluation will require additional studies on individual susceptibility for indirect mutagenic effects and on interactions of aneugens in complex mixtures.

Animals↗

PubMed2005

A risk severity index for industrial plants and sites.

A risk index (Risk Severity Index, S) has been devised to allow the assessment of the risk level originated by a given installation or site over the affected zone. A set of threshold levels for thermal radiation, toxic concentration and overpressure, together with the probabilities and frequencies associated to critical events and their effects have been the basis for calculating the values of S. A computer tool has been designed to perform a quick calculation of the diverse Risk Severity Indexes (for a critical event, for a dangerous phenomenon, for a type of effect and for the whole installation) and to plot a map of the risk severity levels around the site. The methodology has been applied to diverse test cases and it has proved to be useful for risk assessment, for comparative studies and for land use planning.

Accidents, Occupational↗

PubMed2004

Qualitative and quantitative evaluation of bird-specific IgG antibodies.

BACKGROUND: Exposure to organic dust produced by birds often gives rise to an immune response, e.g. IgG antibodies, but intense exposure can lead to high concentrations of IgG antibodies and the development of allergic alveolitis, often known as "bird fancier's lung". The aim of this study was to establish the distribution of bird-specific IgG antibodies in exposed and nonexposed individuals and compare a nonquantitative and quantitative method in evaluating raised levels of IgG antibodies. METHODS: Sera were collected in Sweden and South Africa and levels of IgG antibodies specific to pigeon, budgerigar and parrot antigens were quantified using the UniCAP system. Results were compared to the precipitation in gel assay. The IgG antibody values of symptomatic patients without precipitating antibodies (non-PP group; n = 51) and patients with precipitating antibodies (PP group; n = 34) were analyzed and compared to nonexposed asymptomatic blood donors (BD group; n = 73) and environmentally exposed pigeon breeders (n = 11). RESULTS: The IgG antibody response of the analyzed groups in Sweden and South Africa did not vary significantly from each other. IgG antibody responses were the strongest to pigeon antigens with clear increased IgG antibody levels in the PP group [geometric mean (GM) 603 mg/l] compared to the non-PP (GM 6.9 mg/l) and BD group (GM 5.0 mg/l). Threshold values, calculated as the GM value from the BD group plus 3 standard deviations (99% confidence interval), were 9.8, 10.8 and 10.0 mg/l for pigeons, budgerigars and parrots, respectively. Comparison of the two methods resulted in a good concordance with a level of agreement of 94.1% (kappa statistic = 0.83). CONCLUSIONS: The UniCAP system for the detection of bird-specific IgG antibodies is a highly reproducible, generally available, quantitative method for routine diagnostic testing and monitoring of exposed subjects with a very high level of agreement to the precipitating gel assay.

Alveolitis, Extrinsic Allergic↗

PubMed2004

Occupational exposure to chemical agents in the paper industry.

As part of an International Agency for Research on Cancer (IARC) international epidemiological study of workers in the pulp and paper industry, previously unpublished exposure measurements were assembled in a database. This article summarizes the results of 3,873 measurements carried out in the production departments of paper and paperboard mills and recycling plants in 12 countries. In the paper and paperboard mills, most of the agents were measured in the pulping and refining departments and in on-machine coating and winding of paper/paperboard. Exposures to asbestos, carbon monoxide, formaldehyde, fungal spores, bacteria, nitrogen dioxide, minerals dusts, paper dust, sulphuric acid and different solvents sometimes exceeded exposure limit values. In the re-pulping and de-inking departments of recycling plants high exposures to formaldehyde, fungal spores, bacteria and paper dust were observed. High exposures to asbestos, bioaerosols, carbon monoxide and paper dust were found in many departments; ammonia, formaldehyde, mineral and paper dust and solvents were found in coating machines; and diphenyl and polychlorobiphenyls (PCBs) were found in some special circumstances. Measurements in the newsprint and uncoated paper machine departments revealed only a few elevated exposures. In nearly all departments, measurements of epichlorohydrin, PCBs, sulphur dioxide, hydrogen sulphide and mercaptans tended to be low, often even below their detection limits. In spite of some uncertainties in the measurement data, the study provides new insights into the level and variation of occupational exposures of production workers in the paper and paperboard industry.

Europe↗

PubMed2005

The AETL methodology as a potential solution to current challenges associated with the development and use of acute exposure levels in Seveso II applications.

This paper analyses current trends in the development and use of acute exposure levels in Europe for the implementation of the Seveso II Directive [Council Directive 96/82/EC of December 9, 1996 on the control of major-accident hazards involving dangerous substances. Official Journal of the European Communities, vol. L 10, January 14, 1997, Luxembourg, pp. 13-33]. It also describes a new initiative to develop a European methodology for deriving acute exposure threshold levels that responds to emerging needs in this area. The need for acute exposure values to predict human health effects of potential accidents on exposed populations has burgeoned in recent years. As the driving legislation for managing industrial hazards in Europe, the Seveso II Directive has particularly influenced this trend. Yet at this time it is questionable whether the availability and range of acute exposure values for toxic substances has kept apace with the growing need. Results of a survey of Seveso II competent authorities in the EU-15 revealed that a variety of different types of acute exposure values (AEGLs, EPRGs, etc.) are used for Seveso II applications. Moreover, a comparison of these values indicates gaps in coverage of substances as well as inconsistencies in terms of how health effects and exposure periods are defined for each type. These findings highlight an opportunity for greater collaboration on scientific inputs to application of the Directive in Europe. The ACUTEX project is an EU-funded research project aimed at furthering scientific exchange and collaboration in support of the development of acute exposure levels for toxic substances in Europe. Its goal is to develop a European methodology for deriving acute exposure threshold levels (AETLs). In particular, it provides the possibility for a common European platform for developing additional acute exposure values to meet emerging needs and cover more chemical substances. To maximise success, the work plan is designed to meet two very important challenges, the need to complement and add value to the existing array of acute exposure methodologies and the necessity of meeting requirements of a diverse range of European stakeholders. As such the project will draw on collaboration among European scientists and process of deliberation among stakeholders to deliver the following key results: (1) to facilitate wide acceptance of the methodology in Europe by both the scientific community and communities of different end-users; (2) to provide greater equivalence and transparency in implementation of the Seveso II Directive across the Member States, specifically through the development of common scientific bases for assessing risks and making risk management decisions related to toxic releases; (3) to produce a methodology that remains open to future collaboration on derivation of acute exposure levels on a European and a global basis.

Accident Prevention↗

PubMed2001

Biological monitoring and exposure to mercury.

Occupational health professionals' interest in controlling mercury (Hg) exposure, and the use of biological monitoring in this context, has been ongoing for a number of years. Evidence from urinary Hg results in a number of UK firms who have undertaken some form of biological monitoring or occupational health surveillance suggest that exposure has decreased over the last 10-15 years. This decrease precedes the establishment in the UK of an advisory biological monitoring guidance value (HGV) for urinary Hg and the production of updated medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996). This latter document recommends a urinary sampling interval for urinary Hg of between 1 and 3 months, which is consistent with the reported toxicokinetics of Hg excretion, but we highlight that urinary Hg represents integrated exposure over many previous months. Mercury is a recognized nephrotoxin and MS12 1996 mentions the use of regular dipstick protein estimations. We review our experience of investigating proteinuria and enzymuria in a large-scale cross-sectional occupational study. The incidence of Hg-induced renal disease is probably very rare at current exposure levels. Therefore acceptance of a high false-positive rate of proteinuria not related to Hg exposure needs to be considered in any urinary protein testing regime of Hg workers. The establishment of an HGV for urinary Hg has raised questions about the uncertainty associated with a urinary Hg result, including factors such as diurnal variation, whether urine correction by creatinine or specific gravity is preferable and the possibility of non-occupational sources of Hg contributing significantly towards breaching the HGV. Correction of urinary Hg results by creatinine or specific gravity and the use of a fixed sampling time, such as the beginning or end of the day, substantially reduce the uncertainty in a urinary Hg measurement. But even with good laboratory precision, an individual with a true urinary Hg excretion of 20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol creatinine. The influence of dietary sources in the UK contributing to urinary Hg values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic cosmetics and remedies needs to be considered if a urinary Hg result looks inappropriately high, as some such preparations have been found to contain Hg and can be absorbed through the skin. The ability of excessive chewers or teeth grinders who have a large number of dental amalgam fillings to breach the urinary HGV in the absence of substantial occupational Hg exposure has been reported in a few Scandanavian studies. We report here a likely case of this phenomenon. Since the establishment of the HGV, our biological monitoring Hg data from a number of industry sectors using inorganic or metallic Hg have suggested that a minority of samples (13%) are still greater than the HGV.

Cross-Sectional Studies↗

PubMedDate not supplied

Adjustment of permissible exposure values to unusual work schedules.

Research activities sought development of a method to adjust exposure limits for 694 substances for unusual work schedules. A consensus was established on the basic toxicological principle for adjustment; criteria for adjustment were selected by a panel of scientists coordinated by a committee of international experts and supported by toxicokinetic modeling; and a group of toxicologists attributed primary health effects and related adjustment category to each substance. A consensus among scientists and employers' and workers' representatives was established on the protocol of the application, in the field, of the adjusted exposure limits. The guiding toxicological principle for adjusting exposure standards to unusual work schedules is to guarantee an equivalent degree of protection for workers with unusual schedules as for workers with a conventional schedule of 8 hours per day, 5 days per week. The process of the adjustment is inspired from the Occupational Safety and Health Administration logic for attribution of primary health effects and adjustment categories ranging from no adjustment to daily or weekly adjustments. The adjusted exposure limits are calculated according to Haber's rule. Decisions on attribution of adjustment categories for the following toxicological effects were reached: respiratory sensitizers (asthma); skin sensitizers; tissue irritants versus tissue toxicants; methemoglobinenia-causing agents; cholinesterase inhibitors; and reproductive system toxicants and teratogens. A simple procedure is presented to facilitate the calculation, application, and interpretation of the adjusted exposure limits.

Guideline Adherence↗

PubMedDate not supplied

[Evolution of industrial toxicology toward vanishing doses and the human genome].

BACKGROUND: This article aims to discuss the influence that the application of the recent discoveries in genomics will have on the theory and practice of industrial toxicology in developed post-industrial countries. It is stressed that the recent advances in toxicogenomics can be integrated into the existing wealth of knowledge on the toxic properties of industrial chemicals to improve the efficacy of prevention of toxicological risk. METHODS AND RESULTS: The understanding of the biochemical and physiological mechanisms underlying susceptibility or resistance to the toxic effects of industrial xenobiotics, and in particular to carcinogens, allows us to split the epidemiologically derived relationship linking the frequency of disease in the exposed population to the level of workplace contamination into a set of sequential sub-relationships linking: a) the exposure level to that of workplace contamination; b) the internal dose to the exposure level; c) the biological effect (e.g., measured through biochemical markers of early effect) to the internal dose; d) the frequency of disease to that of observation of early biochemical effects. Each of the cited relationships is affected by a degree of uncertainty due to the variability of biological response among the examined individuals, which in turn requires a definition of the statistical limits for the association functions between the variables. As a consequence, the possibility of investigating the individual biochemical and physiological steps in the causal mechanism that links toxic exposure to disease does not necessarily lead to an increase in the information potential of biological monitoring, since the uncertainty due to inter-individual variability is amplified through the sequence of causal relationships to the point that the data from biological monitoring become valueless with regard to the prediction of the frequency or probability of disease. This is particularly true when exposure to 'low doses' is investigated, as is now increasingly frequent in post-industrial developed countries, where workplace contamination is now greatly reduced to levels which may be borderline with those in the general environment. Thus at the low-dose end of the range of contamination and exposure values there is an area where, for statistical reasons consequent to the heterogeneity of examined populations, a quantitative prediction of internal exposure due to environmental contamination, of biological adverse effects due to exposure levels and of frequency of disease due to the extent or frequency of biological effects is no longer reliably possible. This in turn impairs the preventive efficacy of biological monitoring. CONCLUSIONS: A closer integration between industrial toxicology and state-of-the-art molecular genetics derived from the recent sequencing of the human genome is the way to overcome the limitations described. In particular, the individual subjects in the examined populations can be classified with regard to some genetically controlled characters relevant to the biotransformation of xenobiotics and to DNA repair and the statistical analysis of data can be performed on more homogeneous subpopulations, in order to decrease inter-individual variability of biochemical and physiological response. This in turn increases the predictive power of the biological markers, both of dose and effect, and improves the efficacy of prevention, e.g., by highlighting oversensitive subpopulations or lifestyles which can increase the risk of occupational and environmental disease.

Carcinogens, Environmental↗