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Effects of exposure to low concentrations of chlorinated hydrocarbons on the kidney and liver of industrial workers.

An assessment has been made of biochemical alterations in renal and hepatic functions of 73 male operators employed for an average of 8.2 years (range 0.5-23 years) in a chemical plant producing chlorinated hydrocarbons. Exposure to allyl chloride (AC), 1,3-dichloropropene (DCP), epichlorohydrin (ECH), and hexachlorocyclopentadiene (HEX) has regularly been determined by personal air monitoring since 1980. Although exposures to DCP and ECH were well below currently accepted maximum allowable concentrations (MACs), relatively high exposures to AC and HEX, occasionally exceeding the MAC, have been measured. The results of the kidney and liver function tests were compared with those of a control group comprising 35 men employed at the materials division and not occupationally exposed to chemicals. Biochemical alterations of liver function were assessed by determination in serum of alanine and aspartate aminotransferases (ALAT, ASAT), alkaline phosphatase (AP), total bilirubin (BIL), gamma-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), and total bile acids (SBA). No differences between the exposed group and the control group were found. Nor were differences found in biochemical tests for renal tubular damage (urinary alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) and renal tubular function (urinary retinol binding protein (RBP). Total urinary protein and albumin excretion were measured to assess the integrity of the glomerulus. Urinary total protein did not differ between the groups, but urinary albumin, although within normal limits in both groups, was significantly higher (p < 0.02) in the exposed group. This difference in urinary albumin could not simply be explained by exposure to chlorinated hydrocarbons because albumin concentrations did not correlate with the duration of employment. It is concluded that long term exposure to concentrations of AC, DCP, ECH, or HEX below or near the current limit threshold value does not lead to clinically significant effects on kidney and liver.

Adult↗

Estimating factors to convert Chinese 'Total Dust' measurements to ACGIH respirable concentrations in metal mines and pottery industries.

Historical data on the dust exposures of Chinese workers in metal mines (iron/copper, tin, tungsten) and pottery industries are being used in an ongoing joint Chinese/United States epidemiological study to investigate the exposure-response relationship for the development of silicosis, lung cancer, and other diseases. The historical data include 'total dust' concentrations determined by a Chinese method. Information about particle size distribution and the chemical and mineralogical content of airborne particles is generally not available. In addition, the historical Chinese sampling strategy is different from a typical American eight-hour time-weighted average (TWA) sampling strategy, because the Chinese samples were collected for approximately 15 minutes during production so the sample could be compared to their maximum allowable concentration (MAC) standard. Therefore, in order to assess American respirable dust exposure standards in light of the Chinese experience, factors are needed to convert historical Chinese total dust concentrations to respirable dust concentrations. As a part of the joint study to estimate the conversion factors, airborne dust samples were collected in 20 metal mines and 9 pottery factories in China during 1988 and 1989 using three different samplers: 10mm nylon cyclones, multi-stage 'cassette' impactors, and the traditional Chinese total dust samplers. More than 100 samples were collected and analysed for each of the three samplers. The study yielded two different estimates of the conversion factor from the Chinese total dust concentrations (measured during production processes) to respirable dust concentrations. The multivariate analysis of variance (MANOVA) reveals that, with a fixed sampling/analysis method, conversion factors were not statistically different among the different job titles within each industry. It also indicates that conversion factors among the industries were not statistically different. However, the two estimates consistently showed that conversion factors were the lowest in the pottery industry. Average conversion factors were then calculated for each of the estimates across the industries studied. A pooled mean conversion factor, 0.25+/-0.04, was then derived for all the job titles and industries. Respirable dust levels were estimated from the historical 'total dust' concentrations collected between 1952 and 1992 by adopting the American standard.

Air Pollutants, Occupational↗

Kinetics of elimination of mesitylene and 3,5-dimethylbenzoic acid after experimental human exposure.

The possibility of evaluating occupational exposure to mesitylene based on the determination of unchanged solvent in capillary blood or 3,5-dimethylbenzoic acid in urine was investigated. The volunteers were exposed to mesitylene in a toxicological chamber (range 10-150 mg/m3). Concentrations of solvent or its metabolite in biological material were determined by gas chromatography. The toxicokinetic data concerning retention in the lung, absorption and elimination of mesitylene and its metabolite in biological fluids were obtained. The highest correlation coefficient value was obtained for the relationship between the absorbed dose of mesitylene and the excretion rate of 3,5-dimethylbenzoic acid in urine (r = 0.95). The biological indices of exposure for mesitylene have been proposed, taking the maximum allowable concentration (MAC) value in Poland (100 mg/m3) as the basis.

Air Pollutants↗

High nutrient intakes--the toxicologist's view.

At sufficiently high intake all substances, including essential nutrients, can be toxic. Toxicity may be described by characteristics of the symptoms (identity, severity and degree of persistence) and by the dose-response relationship (threshold, slope, limit, susceptibility to modulation by other substances and tendency to bioaccumulate). Some nutrient toxicities are deleterious exaggerations of essential functions, whereas others are not. The therapeutic indices for nutrients should be defined as the ratio of the lowest toxic dose to the recommended intake, the ratio of the medians of the effective and the toxic doses commonly used in pharmacology. For infant formulas, a ratio of the lowest toxic concentration to the maximum concentration allowed is an analogous ratio. Nutrients with low therapeutic indices and small physical size of a toxic dose require special caution to avoid excessive intake. Modulation of absorption, metabolism or excretion, as well as the physiological state of the exposed individual, may alter the minimum toxic intake of a nutrient and hence alter the risk of toxicity. Extrapolation to estimate the toxic dose can be made on the basis of body weight, body surface area or food intake. Nutrient minimums and maximums in infant formula are set on a 100-kcal basis and thus are related to heat loss and surface area. Evaluation of vitamin A toxicity cases on a dose per 100-kcal basis suggest that the current maximum in infant formula is appropriate. Extrapolation from toxicity data in adults can be made on the dose per 100-kcal basis to estimate appropriate infant formula maximums for nutrients for which maximums have not been set.

Adult↗

[Hygienic regulation of environmental air pollution with consideration of epidemiological data].

The authors hold that the maximum allowable concentrations (MAC) established in Russia for some ambient air pollutants can adversely affect human health and that they are worthy of reconsideration. This opinion is based on the published results of epidemiological studies of Western investigators and on the authors' own data obtained from the analysis by the time series method for a relationship of daily variations of dust or gaseous ambient air pollution to the so-called acute mortality or for that of the variations to respiratory symptoms and to the values of the maximum expiratory flow rate in preschool with or without respiratory abnormalities in their history; from the cross analysis of an association of the characteristics of atmospheric contamination in 13 urban areas with the prevalence of chronic respiratory diseases in junior schoolchildren, which was established by a special questionnaire. Particular emphasis should be laid on the reconsideration of not only established values, but mainly on the principles in laying down MAC for dust particles. The Western practice in measuring and evaluating risks separately for fractions of particles of varying sizes should be assessed for its use in Russian conditions; however, the authors' experience argues for this practice.

Air Pollutants↗

Toxicity of sediments from around a North Sea oil platform: are metals or hydrocarbons responsible for ecological impacts?

Discharges of contaminated drill cuttings have caused appreciable ecological change of the benthos adjacent to many oil and gas platforms in the North Sea. Many platforms have large piles of cuttings lying beneath them and these probably present the greatest potential hazard to the environment during platform decommissioning and removal. There is, however, a lack of consensus on which aspects of drill cuttings are responsible for the adverse ecological effects. This hinders risk assessment of management options. Here we report data on the toxicity of sediments from around the North West Hutton platform to the amphipod Corophium volutator, the polychaete Arenicola marina and the Microtox" acute test system. Sediment was acutely toxic to Corophium out as far as 600 m from the platform. Sediment from 100 m from the platform remained acutely toxic to Corophium when 3% contaminated sediment was mixed with clean sediment. A 10% dilution of this sediment also inhibited Arenicola feeding almost completely. Sediment elutriates did not inhibit Microtox light output, but organics extracted by dichloromethane were very toxic. Fifteen minute EC50 values were as low as 0.25 mg ml(-1) and were strongly correlated with hydrocarbon concentrations. Metal concentrations in whole sediments were correlated with their toxicity to Corophium but the relationship was much weaker when data on dilutions were included. Except at sites immediately adjacent to the platform, metal concentrations were well below ERL values from the literature, so were too low to explain sediment toxicity. Toxicity of sediments to Corophium was closely correlated with their hydrocarbon content, even when tests on dilutions were included in the analysis. We conclude that hydrocarbons are the most significant cause of toxicity in these sediments contaminated with oil based drill cuttings and that polar organics, sulphide. ammonia and other water soluble substances are of much lower significance. Applying OSPAR guidelines to our data on the toxicity of cuttings pile material to Corophium data would give a maximum allowable concentration of 0.03% in clean sediments. The Microtox data indicate that sediments from deeper in the pile would require an even greater dilution than this.

Animals↗

[Effects of exposure to low-level benzene and its analogues on reproductive hormone secretion in female workers].

OBJECTIVE: To study the effects of exposure to low level of mixed benzene on reproductive hormone secretion during menstrual cycle in female workers. METHODS: Concentrations of benzene, toluene and xylene in the expiratory air of 50 exposed female workers from their breathing zone were determined with gas chromatography. Their menstrual cycles of 50 exposed workers and 35 internal control and 35 external control workers were studied prospectively. Urine pregnandiol-3-glucuronide (PdG), follicle stimulating hormone (FSH) and estrone conjugate (E1C) were measured by enzyme immunoassay. RESULTS: Mixed benzene existed mainly in the form of low-level benzene in the air of workplaces, with a detection rate of 29.10% at an average level of 8.88 (0.90-876.47) mg/m3, and 21% of measurements exceeded the national maximum allowable concentration with the highest one as 20.91 folds high as that of the national hygienic standard. Length of luteal phase in the exposed group (13.7 +/- 1.5) days was significantly shorter than that in the internal and external control groups (14.5 +/- 1.2) days and (15.2 +/- 1.1) days (P < 0.05 or P < 0.01). Urine level of E1C before ovulation, that of FSH at early follicular phase and that of PdG in luteal phase after ovulation in the exposed group were significantly lower than those in the internal control group (P < 0.05 or P < 0.01). CONCLUSION: Exposure to low level of mixed benzene in workspaces could interrupt the function of hypothalamic-pituitary-ovarian axis and affect their normal levels of FSH, PdG and E1C.

Adult↗

Evaluation of an automated spectrophotometric assay for reactive oxygen metabolites in serum.

The in vivo assessment of free radicals concentration is hampered by their instability and extremely short half-life. The Diacron Reactive Oxygen Metabolites (D-ROM) test is a recently introduced method to evaluate the peroxidation of organic compounds. Since the manual performance of the test provides excessive analytical imprecision, the aim of this study was to evaluate the automation of this test. Within- and between-run imprecision and interference were assessed according to the guidelines proposed by the NCCLS. The reactive oxygen metabolites' (ROM) stability was evaluated in different physical conditions. For within-run and between-run imprecision the coefficients of variation were consistently lower than 5%. The maximum allowable concentration was 28.2 mmol/l, 0.068 mmol/l and 171 mmol/l for triglycerides, haemoglobin and bilirubin, respectively. Serum storage at -20 degrees C provided adequate ROM stability for up to 3 months, whereas storage at 4 degrees C yielded non-reproducible results. In conclusion, our data provide evidence that the D-ROM assay has both an acceptable stability and an adequate imprecision. The automated assay may be regarded as a fast and reproducible method for the quantitative evaluation of oxidative stress. Since it is easily performed, the method is suitable for routine in clinical laboratories and may provide an accurate estimation of oxidative stress in vivo.

Automation↗

New peat bog record of atmospheric lead pollution in Switzerland: Pb concentrations, enrichment factors, isotopic composition, and organolead species.

A peat core collected at Etang de la Gruère, an ombrotrophic bog in the Jura Mountains of Switzerland, was analyzed for organolead species (DEL, TEL, DML, and TML) using GC-MIP AES, Pb isotopes using TIMS, and total Pb using XRF and age-dated using 210Pb. The earliest occurrence of quantifiable alkyllead is found at a depth of 24 cm, which is dated at AD 1946 +/- 3; this finding is consistent with the introduction of leaded gasoline in Switzerland in 1947. The maximum concentration of alkyllead (2.89 ng/g) is found at 5 cm, which is dated at AD 1988 +/- 2. This same sample yielded 206Pb/207Pb = 1.1254, which is the least radiogenic value in the entire 2K core and comparable to the isotopic composition of Pb in leaded gasoline. The highest concentrations of DML (906 ng/g) and DEL (1906 ng/g) also were found in this sample. Total alkyllead never accounts for more than 0.02% of total Pb in any given sample. The spatial and temporal variations in organolead species is matched by the changes in the isotopic composition of Pb over the same interval. Despite this, the decline in anthropogenic Pb pre-dates the maximum in total alkyllead and minimum 206Pb/207Pb, indicating that atmospheric Pb emissions had already begun their decline prior to the introduction of unleaded gasoline. In fact the decline in anthropogenic Pb was probably in response to the introduction of legislation, first in Germany and later in the European Union, establishing a maximum allowable concentration of Pb in gasoline.

Air Pollutants↗

Critical examination of trace element enrichments and depletions in soils: As, Cr, Cu, Ni, Pb, and Zn in Swiss forest soils.

The aim of this study was to obtain an overview of trace element concentrations in Swiss forest soils and to critically assess the measured values with respect to anthropogenic input vs. lithogenic background. Twenty-three sites were selected which represent a broad range of natural forest sites, bedrock material and soil types of Switzerland. At each site, samples were collected from all genetic soil horizons down to a C or B/C horizon. Total concentrations of As, Cr, Cu, Ni, Pb, and Zn in all samples were determined by X-ray fluorescence spectrometry. There were distinct differences in the geological background values estimated from the concentrations measured in the samples from the lowest soil horizon. Background concentrations for Cr and Ni were lowest in granite and gneiss, whereas Pb and Zn were highest in limestone and marl. Enrichment or depletion of the trace elements was assessed using Zr as reference element. Within the same profile, the six trace elements showed completely different enrichment/depletion patterns with depth. The various natural processes and anthropogenic inputs that can lead to these patterns are critically discussed. Based on this critical assessment, pollution of the investigated forest soils was found to be most severe for Pb and Zn and to a somewhat lesser extent for As and Cu, whereas anthropogenic input of Cr and Ni seems to be less important. The data suggest that a critical evaluation of enrichment factors is a better tool to assess soil pollution with trace elements than the use of maximum allowable concentrations (MAC) for topsoil samples. The enrichment factors calculated as described here consider the effects of geological variation on metal abundances whereas the MAC does not. In order to obtain an estimate of soil solution concentrations, water extracts of the samples collected from a subset of 10 soil profiles were analyzed for the same trace elements. Solubility of all elements generally decreased with soil depth. An exception was Cr, Cu, and Ni solubility in the humus layer, which was lower than in the underlying mineral horizon. For all elements, solubility was higher for the collective of soil samples depleted in this element when compared to the samples, in which the element was enriched.

Arsenic↗

New oral salicylates in the therapy of chronic idiopathic inflammatory bowel disease.

Sulfasalazine has been the mainstay of therapy for ulcerative colitis and Crohn's disease of the colon. More recently, it has become clear that 5-ASA is the active moiety of the compound and that the sulfapyridine component is responsible for most of the adverse responses to sulfasalazine. The modes of action of sulfasalazine and 5-ASA have not been determined despite active investigations. There has been great current emphasis on the development of delivery systems to allow maximum concentration of therapeutically active 5-ASA in the colon or other gastrointestinal mucosal locations. Olsalazine accomplishes this goal by creatively coupling two molecules of 5-ASA to each other by a diazo bond. Bacterial azoreductases uncouple the parent drug and deliver 5-ASA to the colonic mucosa. Several pharmaceutical manufacturers have devised variations in mesalamine (5-ASA) coatings designed to release in pH and time-related manners. Oral Rowasa, Claversal, and Asacol accomplish distal delivery with acrylic coating of tablets. Oral Pentasa seems unique in distributing 5-ASA throughout the small bowel as well as the colon by utilization of small ethylcellulose-coated microgranules. For this reason, Pentasa may be particularly useful in the treatment of small bowel Crohn's disease. There are no data to suggest that patients unresponsive to oral sulfasalazine will respond to 5-ASA in any form, although it is possible that better toleration of the 5-ASA formulations will allow more effective dosage levels to be delivered. There are also preliminary data supporting synergism between oral and topical rectal 5-ASA in certain patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Results of clinical-toxicological assessments performed in the Poison Control Centre in Zagreb over a 10-year period.

The aim of this study was to see which harmful substances and which occupational settings most often required toxicological assessment, to evaluate exposure data provided by employers and to see to what extent could this assessment rely on actual measurements of harmful substances in a working environment. We reviewed the documentation that was submitted for toxicological assessment in all patients referred from occupational health physicians between 1992 and 2001. From 1992 to 2001, the Poison Control Centre performed a total of 260 toxicological evaluations of occupational exposure to harmful chemicals. In 162 cases (62%), measurements of harmful substance concentrations in the working environment would have been of primary significance for the best comparison of potential adverse effects and the level of exposure. The most frequent was exposure to organic solvents in the production line and the use of various paints and varnishes, adhesives and thinners in shoe, chemical and metal-processing industry. Follows exposure to respiratory irritants, mostly in plastic and metal processing. However, measurement data of harmful substances in the working environment were available only in 24 cases, that is, in 9% of all documents submitted for toxicological assessment. Exposure to organic solvents is characteristic for a large number of work places in industry and small enterprises in Croatia, and it is necessary to carry out a more comprehensive study about the real levels of exposure and modes of effective control. It is important because the EU regulations on the indicative occupational exposure limits (OELs) of harmful substances in the working environment, that will soon be implemented into Croatian legislation, recommend a reduction of maximum allowable concentrations (MAC) for commonly used solvents.

Croatia↗

Sources, pathways, and relative risks of contaminants in surface water and groundwater: a perspective prepared for the Walkerton inquiry.

On a global scale, pathogenic contamination of drinking water poses the most significant health risk to humans, and there have been countless numbers of disease outbreaks and poisonings throughout history resulting from exposure to untreated or poorly treated drinking water. However, significant risks to human health may also result from exposure to nonpathogenic, toxic contaminants that are often globally ubiquitous in waters from which drinking water is derived. With this latter point in mind, the objective of this commission paper is to discuss the primary sources of toxic contaminants in surface waters and groundwater, the pathways through which they move in aquatic environments, factors that affect their concentration and structure along the many transport flow paths, and the relative risks that these contaminants pose to human and environmental health. In assessing the relative risk of toxic contaminants in drinking water to humans, we have organized our discussion to follow the classical risk assessment paradigm, with emphasis placed on risk characterization. In doing so, we have focused predominantly on toxic contaminants that have had a demonstrated or potential effect on human health via exposure through drinking water. In the risk assessment process, understanding the sources and pathways for contaminants in the environment is a crucial step in addressing (and reducing) uncertainty associated with estimating the likelihood of exposure to contaminants in drinking water. More importantly, understanding the sources and pathways of contaminants strengthens our ability to quantify effects through accurate measurement and testing, or to predict the likelihood of effects based on empirical models. Understanding the sources, fate, and concentrations of chemicals in water, in conjunction with assessment of effects, not only forms the basis of risk characterization, but also provides critical information required to render decisions regarding regulatory initiatives, remediation, monitoring, and management. Our discussion is divided into two primary themes. First we discuss the major sources of contaminants from anthropogenic activities to aquatic surface and groundwater and the pathways along which these contaminants move to become incorporated into drinking water supplies. Second, we assess the health significance of the contaminants reported and identify uncertainties associated with exposures and potential effects. Loading of contaminants to surface waters, groundwater, sediments, and drinking water occurs via two primary routes: (1) point-source pollution and (2) non-point-source pollution. Point-source pollution originates from discrete sources whose inputs into aquatic systems can often be defined in a spatially explicit manner. Examples of point-source pollution include industrial effluents (pulp and paper mills, steel plants, food processing plants), municipal sewage treatment plants and combined sewage-storm-water overflows, resource extraction (mining), and land disposal sites (landfill sites, industrial impoundments). Non-point-source pollution, in contrast, originates from poorly defined, diffuse sources that typically occur over broad geographical scales. Examples of non-point-source pollution include agricultural runoff (pesticides, pathogens, and fertilizers), storm-water and urban runoff, and atmospheric deposition (wet and dry deposition of persistent organic pollutants such as polychlorinated biphenyls [PCBs] and mercury). Within each source, we identify the most important contaminants that have either been demonstrated to pose significant risks to human health and/or aquatic ecosystem integrity, or which are suspected of posing such risks. Examples include nutrients, metals, pesticides, persistent organic pollutants (POPs), chlorination by-products, and pharmaceuticals. Due to the significant number of toxic contaminants in the environment, we have necessarily restricted our discussion to those chemicals that pose risks to human health via exposure through drinking water. A comprehensive and judicious consideration of the full range of contaminants that occur in surface waters, sediments, and drinking water would be a large undertaking and clearly beyond the scope of this article. However, where available, we have provided references to relevant literature to assist the reader in undertaking a detailed investigation of their own. The information collected on specific chemicals within major contaminant classes was used to determine their relative risk using the hazard quotient (HQ) approach. Hazard quotients are the most widely used method of assessing risk in which the exposure concentration of a stressor, either measured or estimated, is compared to an effect concentration (e.g., no-observed-effect concentration or NOEC). A key goal of this assessment was to develop a perspective on the relative risks associated with toxic contaminants that occur in drinking water. Data used in this assessment were collected from literature sources and from the Drinking Water Surveillance Program (DWSP) of Ontario. For many common contaminants, there was insufficient environmental exposure (concentration) information in Ontario drinking water and groundwater. Hence, our assessment was limited to specific compounds within major contaminant classes including metals, disinfection by-products, pesticides, and nitrates. For each contaminant, the HQ was estimated by expressing the maximum concentration recorded in drinking water as a function of the water quality guideline for that compound. There are limitations to using the hazard quotient approach of risk characterization. For example, HQs frequently make use of worst-case data and are thus designed to be protective of almost all possible situations that may occur. However, reduction of the probability of a type II error (false negative) through the use of very conservative application factors and assumptions can lead to the implementation of expensive measures of mitigation for stressors that may pose little threat to humans or the environment. It is important to realize that our goal was not to conduct a comprehensive, in-depth assessment of risk for each chemical; more comprehensive assessments of managing risks associated with drinking water are addressed in a separate issue paper by Krewski et al. (2001a). Rather, our goal was to provide the reader with an indication of the relative risk of major contaminant classes as a basis for understanding the risks associated with the myriad forms of toxic pollutants in aquatic systems and drinking water. For most compounds, the estimated HQs were < 1. This indicates that there is little risk associated with exposure from drinking water to the compounds tested. There were some exceptions. For example, nitrates were found to commonly yield HQ values well above 1 in- many rural areas. Further, lead, total trihalomethanes, and trichloroacetic acid yielded HQs > 1 in some treated distribution waters (water distributed to households). These latter compounds were further assessed using a probabilistic approach; these assessments indicated that the maximum allowable concentrations (MAC) or interim MACs for the respective compounds were exceeded <5% of the time. In other words, the probability of finding these compounds in drinking water at levels that pose risk to humans through ingestion of drinking water is low. Our review has been carried out in accordance with the conventional principles of risk assessment. Application of the risk assessment paradigm requires rigorous data on both exposure and toxicity in order to adequately characterize potential risks of contaminants to human health and ecological integrity. Weakness rendered by poor data, or lack of data, in either the exposure or effects stages of the risk assessment process significantly reduces the confidence that can be placed in the overall risk assessment. (ABSTRACT TRUNCATED)

Animals↗

Pharmacolinetics of fluorocarbon 11 and 12 in dogs and humans.

Blood levels and exhalation bag contents of FC-11 and FC-12 from dogs and humans were used to elucidate the pharmacokinetic model describing the time-course of these agents. The derived pharmacokinetic parameters were in good agreement with the physicochemical properties of these substances. The model was used to estimate the percentage of dose absorbed, which averaged 77 per cent for FC-11 and 55 per cent for FC-12, and to predict the level of FC-11 and FC-12 under a variety of conditions simulating both short- and long-term exposure to the maximum allowable concentrations of these agents. With similar doses, an 8-hour continuous exposure was estimated to produce levels of FC-11 and FC-12 that are much lower than the corresponding levels reported to induce cardiac sensitization in dogs.

Animals↗

Drug delivery to brain by microparticulate systems.

The site specific delivery of chemotherapeutic agents allows maximum concentration of an agent at a desired body site. This area specific drug delivery decreases the unwanted systemic distribution and decreases toxicity of the administered drugs. Blood-Brain Barrier (BBB) is considered to be an obstacle in delivering large number of drugs to brain. The endothelial cells forming the tubular capillaries in the brain are cemented together by intercellular tight junctions. In this way, the BBB has an important role in providing a stable extracellular environment in the central nervous system. Lack of fenestrations, very few pinocytotic vesicles, and more mitochondria are other differences of the brain capillaries which play important role in transport of drugs to brain (Fig.1). The purpose of this paper is to summarise the methods for BBB permeability modifications and to focus on various examples in delivering drugs, especially neuroncology and neuroactive drugs, to brain by microparticulate systems.

Animals↗

Evaluating promulgated refinery effluent standards using artificial streams.

Two-week tests on an Artificial Refinery MIxture (ARM) were conducted on periphyton communities on glass slides in laboratory streams. ARM components, which are present in "typical" refinery effluents, approximate maximum allowable concentrations as promulgated by the 1977 U.S. Environmental Protection Agency (USEPA) guidelines for refinery effluents. ARM concentrations tested ranged from approximately 0.25 to 5 times full strength. The nontaxonomic structural parameters--ash-free dry weight, chlorophyll a, and ATP--indicated that ARM concentrations of 1 to 5X stimulated periphyton colonization rates. ARM concentrations of 0.25 to 5X caused a shift in dominant periphytic algae from diatoms in reference streams to green algae in dosed streams; this resulted in higher pH levels in reference streams, apparently related to photosynthetic activity. Changes in nontaxonomic structural parameters of slides precolonized with periphyton were not sensitive water quality indicators. Dry weight was not a useful biomass indicator due to high levels of suspended solids in ARM. The promulgated 1977 guidelines may be adequate to maintain nontaxonomic structural integrity of periphyton communities, while the 1983 guidelines appear to be adequate to maintain taxonomic integrity.

Adenosine Triphosphate↗

[Quantitative determination of trace metals in frozen fish, fish oil and fish meal (author's transl)].

As a contribution to the discussion on the "Verordnung uber Umweltkontaminanten" (draft) we examined 73 double samples of the frequent types of edible fish and 2 samples each of fish oil and fish meal for their content of arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg). Arsenic was determined photometrically, cadmium and lead by anodic stripping voltammetry and mercury by flameless atomic absorption spectrometry. We found the following average contents (ppm): 0.84 As, 0.003 Cd, 0.08 Pb, 0.06 Hg. The limits (ppm) set up in the draft for a German "Höchstmengenverordnung" (regulation specifying the maximum concentrations allowed) were by far not reached in the case of Cd, Pb, and Hg with all samples while they were fulfilled in the case of As by only 18% of the samples. It seems that the limit for As of 0.5 ppm has been set up too low. In the average, the following proportion applies for the trace contents found: Cd:Hg:Pb:As = 1:20:27:280. Correlations between the contents of trace metals on the one hand and fishing grounds or trawler or sample piece on the other could not be found.

Arsenic↗

[The levels of heavy metals (Cd, Cu, Hg, Ni, Pb, Zn) in brook trouts from the River Leine in the area of Göttingen (West Germany) (author's transl)].

In order to evaluate the load of heavy metals (Cd, Cu, Hg, Ni, Pb, Zn) imposed on the River Leine by the city of Göttingen (medium-sized town) the content of heavy metals in fish samples (which had been collected at two points on the River Leine, upstream, respectively downstream of Göttingen--Fig. 1) were determined by Atomic Absorption Spectroscopy. Analysis of heavy metals in brook trout (total fish, flesh, and liver) showed a statistically significant definite increase in some heavy metals, caused by the sewage from the city of Göttingen. In the flesh only Cd in the liver Cd, Hg and Zn and in the total fish Cd, Cu and Zn had been increased significantly. All the values of heavy metals in the flesh were lower than the suggested maximum allowable concentrations.

Animals↗