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Occupational hygiene measurement strategy in the pharmaceutical industry.

In an industry which handles materials which are biologically active it is necessary to limit the exposure of workers engaged in both research and production to these materials. Part of the control procedure is to be able to demonstrate that whatever system is put in place is effective and remains so. This may require a programme of environmental monitoring. To be effective any monitoring programme must be properly planned and executed. This paper sets out the philosophy and practice of one multinational pharmaceutical company which may stimulate debate in the industry.

Drug Industry↗

[Monitoring of airborne fungus and yeast species in a hospital unit].

OBJECTIVE: To monitor and characterize airborne filamentous fungi and yeasts from abiotic and biotic sources within a hospital unit. METHODS: Collections were carried out on a monthly basis, at two different time periods, from the adult and pediatric intensive care units and surgical center of a hospital in Araraquara, Southeastern Brazil. Collection of airborne fungi was carried out using a simple-stage Andersen sample. The presence of yeasts was investigated in samples taken from the hands and oropharynx of staff members as well as from the surface of beds and doorknobs inside the critical areas. RESULTS: Thirty-two genera of airborne fungi and were recovered from the surgical center and 31 from the intensive care units. Genera most frequently isolated were Cladophialophora spp., Fusarium spp., Penicillium spp., Chrysosporium spp. e Aspergillus spp. During the study period, a new unit was built in the hospital, which coincided with an increase in Cladophialophora spp., Aspergillus spp., and Fusarium spp. colony counts. Yeasts were found in 39.4% of samples obtained from healthcare staff (16.7% from interdigital spaces, 12.1% from nailbeds, and 10.6% from oropharynx) and in 44% of furniture samples, with a predominance of the Candida genus ((C. albicans, C. guilliermondii, C. parapsilosis e C. lusitaniae), followed by Trichosporon spp. CONCLUSIONS: We found a relatively high number of airborne fungi (potentially pathological) in special areas and expressive levels of yeasts in both biotic and abiotic samples. Microbiological and environmental monitoring should be conducted, especially in special areas which include immunocompromised patients, who are more susceptible to the exposure to environmental and staff-derived pathogens.

Air Microbiology↗

Responses of European eel (Anguilla anguilla L.) in two polluted environments: in situ experiments.

European eels (Anguilla anguilla L.) were caged for 8 and 48 h in two polluted areas to assess the contamination cleanup process in the Vouga River 2 years after the official closing of a bleached kraft pulp mill effluent (BKPME; experiment 1), and to monitor the effects induced by contaminated offward fishing harbor waters (experiment 2). Plasma cortisol, glucose, and lactate were evaluated as stress responses. In experiment 1, plasma cortisol, glucose, and lactate increased after 8 h of exposure in site 3, which is located farthest from the deactivated sewage outlet. However, A. anguilla seemed to adapt after 48 h of exposure in site 3, because all three parameters returned to control levels. Plasma glucose also significantly increased after 8 h of exposure at sites 1, 2, and 3, returning to control levels after 48 h. Plasma lactate levels increased after 8 h of exposure at site 3 and after 48 h of exposure at site 1. In experiment 2, A. anguilla exposed to contaminated harbor waters increased their plasma lactate after 8 and 48 h of exposure, whereas their cortisol and glucose plasma were elevated only after 48 h of exposure. The results demonstrate that even 2 years after the official closing of the BKPME sewage outlet, the river Vouga water remains contaminated by the sediment associated chemicals. Because the fishing harbor induced in A. anguilla the same type of stress responses, it is also an area of concern. The adopted stress parameters allied to a caging strategy are recommended for future environmental monitoring assessments.

Anguilla↗

Estimation of the production, consumption, and atmospheric emissions of pentabrominated diphenyl ether in Europe between 1970 and 2000.

A European consumption and atmospheric emissions inventory for pentabrominated diphenyl ethers (PeBDEs) is derived for the period 1970-2000. This time frame has seen a rise in the widespread usage of PeBDE, followed by more recent restrictions/bans. It is estimated that a total of 3000-5000 t of PeBDEs was produced in Europe during this period, with a further 9000-10,000 t imported in finished articles. The main uses for PeBDE are to flame retard consumer products as well as in packaging and solid elastomers. Their major stocks are predicted to be in polyurethane (flexible) foams with up to 30% in cars; more than 10% in furniture foam; and the rest in textiles, building material, packaging, and solid applications. Release of PeBDEs from treated products into environmental media are estimated with a focus on atmospheric inputs via volatilization from their use in cars, upholstered furniture, textiles, television sets, personal computers, and other recycled material. Different emission factors are used to derive different emission scenarios. A peak in atmospheric emissions of between 22 and 31 t of BDE-47 is estimated to have occurred around 1997, with a decline of approximately 20% in 2000. Comparisons with long-term environmental monitoring data revealed that the time trends of human blood and milk concentrations follow similar patterns to the generated emissions, while sediment core levels increase more slowly, probably because they respond to a mix of atmospheric and catchment inputs. The emissions data derived here can be used in a spatially and temporally resolved form as input data for multi-media environmental fate modeling.

Air Pollutants↗

Relationships among exceedences of metals criteria, the results of ambient bioassays, and community metrics in mining-impacted streams.

If bioassessments are to help diagnose the specific environmental stressors affecting streams, a better understanding is needed of the relationships between community metrics and ambient criteria or ambient bioassays. However, this relationship is not simple, because metrics assess responses at the community level of biological organization, while ambient criteria and ambient bioassays assess or are based on responses at the individual level. For metals, the relationship is further complicated by the influence of other chemical variables, such as hardness, on their bioavailability and toxicity. In 1993 and 1994, U.S. Environmental Protection Agency (U.S. EPA) conducted a Regional Environmental Monitoring and Assessment Program (REMAP) survey on wadeable streams in Colorado's (USA) Southern Rockies Ecoregion. In this ecoregion, mining over the past century has resulted in metals contamination of streams. The surveys collected data on fish and macroinvertebrate assemblages, physical habitat, and sediment and water chemistry and toxicity. These data provide a framework for assessing diagnostic community metrics for specific environmental stressors. We characterized streams as metals-affected based on exceedence of hardness-adjusted criteria for cadmium, copper, lead, and zinc in water; on water toxicity tests (48-h Pimephales promelas and Ceriodaphnia dubia survival); on exceedence of sediment threshold effect levels (TELs); or on sediment toxicity tests (7-d Hyalella azteca survival and growth). Macroinvertebrate and fish metrics were compared among affected and unaffected sites to identify metrics sensitive to metals. Several macroinvertebrate metrics, particularly richness metrics, were less in affected streams, while other metrics were not. This is a function of the sensitivity of the individual metrics to metals effects. Fish metrics were less sensitive to metals because of the low diversity of fish in these streams.

Amphipoda↗

Current research activity in biosensors.

Biosensors consist of a molecular recognition element and a transducer. Since the first biosensor was developed by Updike and Hicks many biosensors and their associated techniques have been studied and developed. In this review current research activity on the fundamentals and applications of biosensors is summarized. In discussion of the former, molecular recognition elements, techniques and tools for biosensor construction, and basic biosensor devices are introduced. Coverage of the latter includes description of biosensors for environmental, food, and clinical fields. Chemical sensors developed in our laboratory for environmental monitoring are also described. This review mainly summarizes work performed by our group and by our colleagues, and refers to the main review articles summarizing each field of biosensor research in recent years.

Biosensing Techniques↗

Biochemical effects of vinyl chloride monomer on the liver of occupationally exposed workers.

We investigated the effects of vinyl chloride monomer exposure on the liver of 86 workers by measuring beta-glucuronidase, arylsulfatase A, adenosine deaminase, 5'-nucleotidase and routine liver function enzymes in the sera of the workers. In 21 of them, three or more of these parameters were raised, with a significant decrease in the level of blood glutathione and a significant increase in the enzyme activity level of glutathione S-transferase. Of these 21 workers, 14 had fatty liver infiltration, 8 of whom were also suffering from liver enlargement. Also, 4 workers had liver enlargement without fatty infiltration and 3 had enlarged spleens. The study highlights the need for vigilance in environmental monitoring and medical surveillance of workers exposed to this chemical.

5'-Nucleotidase↗

Chronic beryllium disease and cancer risk estimates with uncertainty for beryllium released to the air from the Rocky Flats Plant.

Beryllium was released into the air from routine operations and three accidental fires at the Rocky Flats Plant (RFP) in Colorado from 1958 to 1989. We evaluated environmental monitoring data and developed estimates of airborne concentrations and their uncertainties and calculated lifetime cancer risks and risks of chronic beryllium disease to hypothetical receptors. This article discusses exposure-response relationships for lung cancer and chronic beryllium disease. We assigned a distribution to cancer slope factor values based on the relative risk estimates from an occupational epidemiologic study used by the U.S. Environmental Protection Agency (EPA) to determine the slope factors. We used the regional atmospheric transport code for Hanford emission tracking atmospheric transport model for exposure calculations because it is particularly well suited for long-term annual-average dispersion estimates and it incorporates spatially varying meteorologic and environmental parameters. We accounted for model prediction uncertainty by using several multiplicative stochastic correction factors that accounted for uncertainty in the dispersion estimate, the meteorology, deposition, and plume depletion. We used Monte Carlo techniques to propagate model prediction uncertainty through to the final risk calculations. We developed nine exposure scenarios of hypothetical but typical residents of the RFP area to consider the lifestyle, time spent outdoors, location, age, and sex of people who may have been exposed. We determined geometric mean incremental lifetime cancer incidence risk estimates for beryllium inhalation for each scenario. The risk estimates were < 10(-6). Predicted air concentrations were well below the current reference concentration derived by the EPA for beryllium sensitization.

Adult↗

[Environment-related health disorders. Experience and perspectives in the care of patients with environment-related health disorders].

Environmental medicine outpatient clinics, counseling centers, and practicing physicians have observed environment-related health disorders in patient groups of mixed age as well as for groups consisting only of adults or children. Practicing physicians suspected correlations between environmental factors and health disorders in 36-45% of cases, environmental medicine outpatient clinics and counseling centers in 4-34% for mixed-age groups, 0-24% for adults, and 9-13% for children. A comparison of these data is difficult due to differences in data acquisition, evaluation methods, and descriptive statistics used. Furthermore, data on children are insufficient. Patient-oriented environmental medicine faces a number of problems regarding determination of exposure, effects, and susceptibility, including a lack of scientifically verified cause-and-effect models as well as incorrect diagnoses, attributions, and conclusions. In view of the scope and intensity of environment-related health disorders, the topic cannot be ignored. A functioning program of environmental medicine counseling and patient care is needed for practicing physicians, universities and/or the public sector to deliver effective primary medical care in this field. As always, the building blocks of environ-mental medicine counseling are medical history, physical examination, differential diagnosis, human biomonitoring, and on-site inspection with environmental monitoring while also taking gender differences into account. Uniform basic documentation procedures and health science analyses will help to optimize patient care in environ-mental medicine. The value of a diagnostic algorithm in the care of patients with environment-related health disorders is beyond dispute. Last but not least, quality assurance and control are a sine qua non of patient-oriented environmental medicine.

Adult↗

Induction of micronuclei in eel (Anguilla anguilla L.) by heavy metals.

Micronucleus test was performed in situ on eels (Anguilla anguilla) from river sites with different levels of heavy metal pollution (cadmium and mercury). Cadmium content in eel liver but not micronuclei averages in kidney were associated with cadmium content in sediments. Mercury content in liver was not significantly associated with mercury content in sediments. Both cadmium and mercury induced micronuclei expression in eels when injected, the concentration tested being 1.7 mg metal/kg body weight and the micronuclei induction being 2.64 and 2.35 micronuclei per 1000 cells for cadmium and mercury respectively. It was concluded that these heavy metals are genotoxic for European eel, that eel liver metal content is a sensitive indicator for environmental monitoring of cadmium pollution, and that the micronuclei scores in eels are not a sensitive method to detect heavy metals pollution in freshwater ecosytems.

Animals↗

[The prevention of tumors in the aluminum industry].

Aluminium industry workers are exposed to various carcinogenic substances, the most important of which are asbestos and coal pitch and tar fumes. Primary prevention of cancer risk can be achieved either by eliminating the carcinogenic agent from the working environment, or by reducing the exposure levels or the number of exposed workers. In the aluminium industry the first type of approach is possible in the case of asbestos, which can be substituted with MMMF (man made mineral fibers), with the cancer risk thus passing from group 1 to group 2b of the IARC Classification. Complete abolition of exposure to pitch and coal-tar fumes is not feasible, but a reduction in risk can be achieved by using the pre-bake anode cell process instead of the Söderberg process, since the former reduces exposure of potroom workers to pitch and coal-tar fumes. A further reduction of exposure in pot-rooms can be achieved, as demonstrated by direct experience in an aluminium plant at Port Marghera (Province of Venice). Environmental monitoring performed from 1978 to 1989 showed a decrease in levels of total dust concentrations and thus of PAH and BaP concentrations as a result of a series of technical and/or organisational improvements. In biological monitoring, which can detect any skin absorption of the carcinogen, the concentrations of urinary hydroxypyrene confirmed low levels of exposure in the plant under study, excluding the pitch plant workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗

[Toxicological analysis at the beginning of the third millennium: promising new applications and future implications].

Enormous progress has been made in clinical toxicology over the last two decades, notably in the detection of pollutants. Chromatographic techniques have now replaced colorimetric reactions, which were non specific and poorly sensitive. Mass spectrometry has largely supplanted immunological methods, and is now coupled to gas phase (GC-MS or GC-MS/MS), liquid phase (LC-MS or LC-MS/MS) or induced coupled plasma spectrometry (ICP-MS). Few substances responsible for clinical syndromes now escape detection, be they medicinal drugs, plant products, pesticides, drugs of abuse, drugs used for criminal purposes, metals, metalloids, or poisons. Forensic medicine has benefited from these advances, notably in the fields of post-mortem toxicology, driving under the influence of drugs of abuse, and drug-facilitated crime. Rapid advances are being made in occupational and environmental monitoring of new substances with poorly documented toxicity. The French National Health and Environment Program, launched on 9 August 2004, specifically takes this problem into account. The author presents recent personal laboratory results illustrating the potential of these new techniques.

Environmental Monitoring↗

Liver damage among shoe repairers.

BACKGROUND: The risk of hepatotoxicity in the shoe industry has already been suggested, however, there has been no investigation among the craftsmen who repair shoes. METHODS: A group of 33 shoe repairers who work in supermarkets, and who use the same glues which contain mixtures of potentially hepatotoxic solvents were identified. A control group of 61 workers not exposed to hepatotoxic substances was also examined. All participants completed a questionnaire designed to identify potential risk factors and the main non-occupational confounding factors for hepatotoxicity. Laboratory tests, commonly used in clinical practice, were done to check whether they were useful markers of hepatotoxicity due to exposure to solvent mixtures, and to investigate which tests should be used in the screening campaigns. RESULTS: The exposed workers had a higher prevalence of elevated mean alanine aminotransferase (ALT), aspartate aminotransferase (AST), conjugated bilirubin (P=0.0001), and alkaline phosphatase (AP) (P=0.004) than controls did. The number of workers who had values outside the upper limit of normal for our laboratory was significantly higher (ALT P=0.034, AST P=0. 037, conjugated bilirubin P=0.014). Exposed workers all had a ratio of ALT to AST greater than 1, with a mean of 1.5; it was > 1.6 in more than half the exposed workers. CONCLUSIONS: The findings suggest that there is the possibility of liver involvement among even asymptomatic shoe repairers, and that periodic liver screening may be useful; furthermore, use of these tests (especially the ratio of ALT to AST) for craftsmen who repair shoes, and are exposed to solvent mixtures, is advisable even when environmental monitoring indicates levels below the threshold limit values (TLVs).

Acetates↗

Biodegradation of the cyclic nitramine explosives RDX, HMX, and CL-20.

Cyclic nitramine explosives are synthesized globally mainly as military munitions, and their use has resulted in environmental contamination. Several biodegradation pathways have been proposed, and these are based mainly on end-product characterization because many of the metabolic intermediates are hypothetical and unstable in water. Biodegradation mechanisms for cyclic nitramines include (a) formation of a nitramine free radical and loss of nitro functional groups, (b) reduction of nitro functional groups, (c) direct enzymatic cleavage, (d) alpha-hydroxylation, or (e) hydride ion transfer. Pathway intermediates spontaneously decompose in water producing nitrite, nitrous oxide, formaldehyde, or formic acid as common end-products. In vitro enzyme and functional gene expression studies have implicated a limited number of enzymes/genes involved in cyclic nitramine catabolism. Advances in molecular biology methods such as high-throughput DNA sequencing, microarray analysis, and nucleic acid sample preparation are providing access to biochemical and genetic information on cultivable and uncultivable microorganisms. This information can provide the knowledge base for rational engineering of bioremediation strategies, biosensor development, environmental monitoring, and green biosynthesis of explosives. This paper reviews recent developments on the biodegradation of cyclic nitramines and the potential of genomics to identify novel functional genes of explosive metabolism.

Amines↗

Human pharmaceuticals in US surface waters: a human health risk assessment.

The detection of low levels of pharmaceuticals in rivers and streams, drinking water, and groundwater has raised questions as to whether these levels may affect human health. This report presents human health risk assessments for 26 active pharmaceutical ingredients (APIs) and/or their metabolites, representing 14 different drug classes, for which environmental monitoring data are available for the United States. Acceptable daily intakes (ADIs) are derived using the considerable data that are available for APIs. The resulting ADIs are designed to protect potentially exposed populations, including sensitive sub-populations. The ADIs are then used to estimate predicted no effect concentrations (PNECs) for two sources of potential human exposure: drinking water and fish ingestion. The PNECs are compared to measured environmental concentrations (MECs) from the published literature and to maximum predicted environmental concentrations (PECs) generated using the PhATE model. The PhATE model predictions are made under conservative assumptions of low river flow and no depletion (i.e., no metabolism, no removal during wastewater or drinking water treatment, and no instream depletion). Ratios of MECs to PNECs are typically very low and consistent with PEC to PNEC ratios. For all 26 compounds, these low ratios indicate that no appreciable human health risk exists from the presence of trace concentrations of these APIs in surface water and drinking water.

Adult↗

Biomarkers and bioassays for detecting dioxin-like compounds in the marine environment.

The presence of toxic chemical contaminants in some marine organisms, including those consumed by humans, is well known. Monitoring the levels of such contaminants and their geographic and temporal variability is important for assessing and maintaining the safety of seafood and the health of the marine environment. Chemical analyses are sensitive and specific, but can be expensive and provide little information on the actual or potential biological activity of the contaminants. Biologically-based assays can be used to indicate the presence and potential effects of contaminants in marine animals, and therefore, have potential for routine monitoring of the marine environment. Halogenated aromatic hydrocarbons (HAHs) such as chlorinated dioxins, dibenzofurans, and biphenyls comprise a major group of marine contaminants. The most toxic HAHs (dioxin-like compounds) act through an intracellular receptor protein, the aryl hydrocarbon receptor, which is present in humans and many, but not all, marine animals. A toxic equivalency approach based on an understanding of this mechanism provides an integrated measure of the biological potency or activity of HAH mixtures. Biomarkers measured in marine animals indicate their exposure to these chemicals in vivo. Similarly, in vitro biomarker responses measured in cell culture bioassays can be used to assess the concentration of 'dioxin equivalents' in extracts of environmental matrices. Here, I have reviewed the types and relative sensitivities of mechanistically-based, in vitro bioassays for dioxin-like compounds, including assays of receptor-binding, DNA-binding and transcriptional activation of native (CYP1A) or reporter (luciferase) genes. Examples of their use in environmental monitoring are provided. Cell culture bioassays are rapid and inexpensive, and thus have great potential for routine monitoring of marine resources, including seafood. Several such assays exist, or are being developed, for a variety of marine contaminants in addition to the dioxin-like chemicals. A battery of cell culture bioassays might be used to rapidly and sensitively screen seafood for the presence of contaminants of concern, including dioxin-like compounds as well as other contaminants such as natural toxins, hormonally active agents, and heavy metals. Such a battery of mechanism-based, in vitro bioassays could be incorporated into monitoring efforts under recently adopted hazard analysis and critical control point (HACCP) programs.

Animals↗

Contribution of agricultural and non-agricultural use of pesticides to the environmental impact on aquatic life in regional surface water systems.

By means of a modelling tool an analysis was made of the local variation in the use of pesticides in the province of Utrecht in The Netherlands, and the potential environmental impact of pesticide emissions on the aquatic ecosystems. The aim of this study was to identify and quantify the major sources of pesticide use and environmental impact, taking the regional variation of pesticide use into account. The analysis was targeted at different levels: detailed (individual active substances, individual agricultural crops, civil land-use types, hydrological catchment basins) and globally covering agricultural use, non-agricultural use (some civil sectors) and recreational shipping. The results can be used for the (re)design of environmental monitoring programmes of pesticides in surface waters and for the development of region based policies towards sustainable pesticide use. The analysis tool that was developed is considered to be applicable for other regions as well.

Agriculture↗

Temporal trends of Cd, Cu, Hg, Pb and Zn in mussel (Mytilus galloprovincialis) from the Spanish North-Atlantic coast 1991-1999.

Temporal trends for heavy metals (Cd, Cu, Hg, Pb and Zn) in mussel (Mytilus galloprovincialis) from the Galician and Cantabrian areas in Spain, where samples were yearly collected from 1991 to 1999, are presented. This study was carried out by the Centro Oceanográfico de Vigo of the Instituto Español de Oceanografia (I.E.O.) as part of the Spanish contribution to the Joint Assessment and Monitoring Programme (JAMP) of the OSPAR Convention. The experimental work and subsequent statistical treatment, following OSPAR procedures and guidelines, are described. In order to carry out the statistical treatment of the data, median values of the different shell length classes were used for each contaminant, year and area. The Kendall T-b correlation coefficient was used with the purpose of demonstrating the existence of a downward significant temporal trend in the pollution levels, according to the advice of ICES Working Group on Statistical Aspects of Environmental Monitoring. A decrease of copper levels was detected in Vigo, Pontevedra and Arosa, of mercury in Pontevedra and A Coruña, of lead in Vigo, Pontevedra, A Coruña and Bilbao and of zinc in Pontevedra and A Coruña. However, a cadmium positive trend was registered at Ria de Vigo. No significant trends were detected in the other cases.

Animals↗