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  • 1. Aitio, Antero
    et al.
    Bernard, Alfred
    Fowler, Bruce A.
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Biological Monitoring and Biomarkers2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 65-78 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Biomonitoring was developed for the assessment of the health risks from exposure to metals at work, and the approaches and concepts of biomonitoring are derived from such exposures. At present, biomonitoring is increasingly used to assess exposure from the environment. Biomonitoring and assessment of external exposure are complementing activities, where the exposure assessments are much more widely applied, especially when the number of chemicals concerned is considered; environmental analysis also offers the distinct advantage of speciation analysis, which is very poorly developed for biomonitoring. Biomonitoring, on the other hand, provides information on exposure from all sources, and via all absorption routes, and also considers accumulation of the chemical in the body. Biomonitoring using exposure biomarkers thus considers interindividual differences in the absorption, whereas use of effect biomarkers also considers interindividual differences in sensitivity. Few effect biomarkers, however, have been validated. Biomarkers of susceptibility have so far not been adapted for use in metal toxicology. The major challenges of biomonitoring are the development of monitoring methods, which are inexpensive enough to be applied at a frequency that makes possible meaningful biomonitoring of metals with a short half-time; development of exposure biomarker guidance values specific to individual species of different metals; expansion of the repertoire of validated effect biomarkers; and validation and application to effect monitoring of the "omic" technologies.

  • 2. Beckett, William S.
    et al.
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Clarkson, Thomas W.
    Routes of Exposure, Dose, and Metabolism of Metals2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 39-64 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    The chapter first describes the main sources of exposure through air, food, and water but also points to unusual sources such as medical implants. Special attention is given to the processes of lung deposition and clearance of inhaled gases, vapors, and particulates, including ultrafine particles. In contrast to the extensive studies in the lung, absorption of metal in the gastrointestinal tract is less well understood. A diagrammatic example is given of the summation of all the absorption processes as they contribute to the total body burden. Since the publication of the first edition, new information has become available on the mechanisms of transport and distribution of metals in the body. In particular, it has been shown that several metals can cross cell membranes by specific carriers and ion channels intended for endogenous substrates. One well-documented example is the chromate oxyanion that is structurally similar to the sulfate anion and thereby gains entrance into the cell by the sulfate carrier. The fecal excretion of several metals occurs as the end result of extensive enterohepatic recirculation. In the case of certain organometallic species, the gut microflora may play a critical role converting the metal to the inorganic form, which is excreted in the feces. The renal accumulation and excretion of metals has also received considerable attention. The renal accumulation of cadmium in the form of its complex with the small molecular weight protein, metallothionein, still remains one of the best-documented mechanisms. Toxicokinetic models continue to be useful in providing a quantitative description of the overall body turnover of metals. They can be useful in establishing dose-response relationships where, for example, the range of half-times of elimination of a metal can contribute to the overall variance in the dose-response relationship. In addition to the observationally based models, pharmacokinetic models can be developed based a priori on physiological and mechanistic considerations. The chapter concludes with a consideration of indicator media that best reflect the dose to the critical organ.

  • 3. Becking, George C.
    et al.
    Nordberg, Monica
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Essential Metals: Assessing Risks from Deficiency and Toxicity2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 163-176 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Recommendations aimed at protecting the public from toxicity of essential elements have usually been developed separately from those recommendations aimed at protection from deficiency. Because of the uncertainties involved in the evaluations, these recommendations have sometimes been in conflict, emphasizing the need for a new approach, including a balanced consideration of nutritional and toxicological data. In developing these new principles of evaluation, some basic concepts based on interindividual variability in sensitivity to deficiency and toxicity must be considered. Such variation translates into one interval of (low) daily intakes, at which there is risk of developing deficiency, and another interval of (high) dietary intakes at which toxicity may occur. In most instances, there is a third set of intakes in between, which represents the acceptable range of oral intakes (AROI) in which no adverse effects occur. It must be noted, however, that such a range cannot be found that protects all persons from adverse effects. Those persons with genetically determined sensitivity may require higher intakes to avoid deficiency or lower intakes to avoid toxicity than those defined by the AROI. AROI is defined as protecting 95% of an unselected human population from minimal adverse effects of deficiency or toxicity.

  • 4.
    Forsberg, Bertil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Pekkanen, J
    Clench-Aas, J
    Mårtensson, MB
    Stjernberg, Nils
    Bartonova, A
    Timonen, KL
    Skerfving, S
    Childhood asthma in four regions in Scandinavia: risk factors and avoidance effects1997Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 26, nr 3, 610-619 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The high and increasing prevalence of childhood asthma is a major public health issue. Various risk factors have been proposed in local studies with different designs.

    METHODS: We have made a questionnaire study of the prevalence of childhood asthma, potential risk factors and their relations in four regions in Scandinavia (Umeå and Malmö in Sweden, Kuopio in eastern Finland and Oslo, Norway). One urban and one less urbanized area were selected in each region, and a study group of 15962 children aged 6-12 years was recruited.

    RESULTS: The prevalence of symptoms suggestive of asthma varied considerably between different areas (dry cough 8-19%, asthma attacks 4-8%, physician-diagnosed asthma 4-9%), as did the potential risk factors. Urban residency was generally not a risk factor. However, dry cough was common in the most traffic polluted area. Exposure to some of the risk factors. such as smoking indoors and moisture stains or moulds at home during the first 2 years of life, resulted in an increased risk. However, current exposure was associated with odds ratios less than one.

    CONCLUSIONS: Our findings were probably due to a combination of early impact and later avoidance of these risk factors. The effects of some risk factors were found to differ significantly between regions. No overall pattern between air pollution and asthma was seen, but air pollution differed less than expected between the areas.

  • 5.
    Forsberg, Bertil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Stjernberg, Nils
    Wall, Stig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Prevalence of respiratory and hyperreactivity symptoms in relation to levels of criteria air pollutants in Sweden1997Inngår i: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 7, nr 3, 291-296 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Our knowledge of the adverse health effects from exposure to low levels of air pollution is still insufficient. Early indicators, such as respiratory symptoms, need more attention. We made use of the fact that possible weak effects can be detected more easily when the relevant exposure and other determinants are well controlled. A postal questionnaire was sent to random samples of inhabitants registered as residing in the Vicinity of 55 centrally located air quality monitoring stations in Swedish towns. There were 6,109 questionnaires (76%) returned. Multivariate analyses with confounding control were used to examine the effects of different levels of criteria pollutants on the prevalence of symptoms. The ranges of the half year values were 9-32 and 2-16 mu g/m(3) for nitrogen dioxide and sulphur dioxide respectively. Logistic regression analyses showed higher risks for respiratory problems such as coughs, throat irritation and nose irritation among the persons most exposed, The associations were most obvious for nitrogen dioxide exposure among women. The suggested effects of air pollution exposure cannot be medically evaluated today but they are nevertheless interesting since they are found within common levels usually considered to be safe.

  • 6. Holler, James S.
    et al.
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Fowler, Bruce A.
    Silver2007Inngår i: Handbook on the Toxicology of Metals, 3rd edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 809-814 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Silver compounds may be absorbed through inhalation, but there are no quantitative human data on the extent of this phenomenon. Silver salts may be absorbed by up to 10-20% after ingestion. The highest concentrations of silver are usually found in the liver and spleen, and to some extent in the muscles, skin, and brain after ingestion. The biological half-time for silver ranges from a few days for animals up to approximately 50 days for the human liver; it is possible that skin deposits have an even longer half-time, but there are no quantitative data on this for man. Silver binds to high-molecular-weight proteins and metallothionein in tissue cytosol fractions. Excretion of silver from the body is primarily biliary. Water-soluble silver compounds such as the nitrate have a local corrosive effect and may cause fatal poisoning if swallowed accidentally. Chronic exposure of humans leads to argyria, a clinical entity characterized by grey-blue pigmentation of the skin and other body viscera. Repeated exposure of animals to silver may produce anemia, cardiac enlargement, growth retardation, and degenerative changes in the liver.

  • 7. Hu, Yunping
    et al.
    Jin, Taiyi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Zhou, Tong
    Pang, Bing
    Wang, Yunfei
    Effects of zinc on gene expressions induced by cadmium in prostate and testes of rats2004Inngår i: Biometals, ISSN 0966-0844, E-ISSN 1572-8773, Vol. 17, nr 5, 571-572 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 8.
    Jarl, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin. Work Science, The Royal Institute of Technology, Stockholm; The Swedish Foundation for Occupational Health and Safety for State Employees ("Statshälsan"), Karlskrona, Sweden.
    Serious occupational injuries by "accidents": possible means of prevention and injury mitigation1989Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    An analysis of the circumstances preceding severe occupational injuries as a consequence of impacts has shown that well-known risks are of great importance in 75 per cent of the cases. This indicates that the subjective cause "neglect" is common. The negligence is distributed to the same extent among employers as among employees. Negligence by the employers was defined as obvious violations according to the Law of Workers’ Safety or Regulations issued by The National Board of Occupational Health and Safety. Negligence by employees was defined as actions against specific orders or common sense.

    As a result of this study additional research concerning the execution of Criminal Law in occupational accidents has been carried out. The law has also been changed regarding prosecution in cases of breaking the Law on the working environment.In situations where elimination of risks is not possible it is a most important task to minimize the risk of severe injury. In four of the studies there are examples of minimization of injuries by increased usage of personal safety equipment, improved rescue and by modifying the environment.

    If personal safety equipment could be used in all relevant situations the incidence of severe injuries at the place of work would decrease by more than 25 per cent. However, the crucial insufficiencies as to the specifications of personal protective equipment must be emphasized. This should stimulate the development of environmental changes, thus preventing the build-up and release of potentially dangerous energy.

    Working alone and late rescue for other reasons, together with other circumstances following the injury made the injuries worse in a little more than 10 per cent of the cases.In the studies concerning injuries as the result of impacts in trucks and buses it is shown that a lot of trucks turn over and that a large number of injuries occur as a result of deformation of the cabins. A safety belt would offer good protection against injury in about half of the cases. Safety in trucks and buses could be improved by the introduction of a deformative zone in front of the occupants.

    Front designs of cab-over vehicles should be changed and the use of seat belts in trucks and buses should be made compulsory. Passive seat belts, knee bars and air bags are interesting alternatives and additions to manual seat belts for commercial drivers.

  • 9.
    Jin, Taiyi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin. Fudan University, School of Public Health, Department of Occupational Health, Shanghai 200032, Peoples Republic of China.
    Chen, Liang
    Lei, Lijian
    Nordberg, Monica
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    An invited paper presented in the symposium "Health effects of low dose exposure to toxic metals"2008Inngår i: Cell Biology and Toxicology, ISSN 0742-2091, E-ISSN 1573-6822, Vol. 24, nr 5, 451-455 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 10.
    Lagerkvist, Birgitta Json
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Systemic effects of occupational exposure to arsenic: with special reference to peripheral circulation and nerve function1989Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Smelter workers who were exposed to air-borne arsenic for a mean of 23 years, and age-matched referents, were examined with clinical, physiological, and neurophysiological methods. Exposure to arsenic in workroom air was estimated to have been around the Swedish occupational limits, which were 500 yg/m before 1975 and 50 yg/ra thereafter. An increased preval ence of Raynaud's phenomenon and a reduced finger systolic blood pressure (FSP) during local and general cooling were found in the smelter workers. Slight, but significant sub-clinical neuropathy, in the form of slightly reduced nerve conduction velocity (NCV) in two or more peripheral nerves, was more common among the arsenic workers than among the referents. There were positive correlations between cumulative exposure to arsenic, reduced NCV in three peripheral motor nerves, and decrease in FSP during cooling. Arsenic levels in urine were 1 ymole/1 (75 yg/1) in the arsenic workers and 0.1 ymole/1 in the referents. In 21 arsenic workers with no or very low exposure to vibra ting hand tools, the FSP during cooling had increased significantly after 3 years wit h the lower arsenic exposure. There was no change in FSP during the summer vacation, whereas urinary levels of arsenic decreased to normal values. Thus there seems to be a slow improvement of finger blood circ ulation which is independent of short-term fluctuations in the exposure to arsenic. No seasonal variation was found in FSP during cooling with the standardized method used. When the NCV-measurements were repeated five years later the difference between arsenic workers and referents had increased, despite the fact that 14 of the 47 arsenic workers had had no exposure to arsenic during the last 1-5 years. These observations indicate, that in subjects with long term exposure to arsenic, sub-clinical neuropathy is not reversible. Ten milligrams of Ketanserin, a serotonin receptor antagonist, was given intravenously to five arsenic workers with cold-induced vasospasm. Skin temperature and FSP during cooling increased significantly with Ketanserin as compared wit h saline solution. After oral treatment, 2 x 40 mg /day for four weeks, no significant increase of FSP during cooling or rise in skin temperature was found in six arsenic workers and eleven patients with Raynaud's phenomenon. The decrease of vasospastic tendency after intravenous injection of Ketanserin indicated that similar mechanisms might operate in arsenic-induced and other types of Raynaud's phenomenon. A general co nclusion from the five studies in this dissertation is that long-term occupational exposure to arsenic has had adverse effects on the peripheral circulation and nerve conduction. The tendency to vasospasm, but not the sub-clinical neuropathy, seemed to be reversible with decreasing exposure.

  • 11.
    Lagerkvist, Birgitta J-Son
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Oskarsson, Agneta
    Department of Biomedical Sciences and Veterinary Public Health Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala.
    Vanadium2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 905-923 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Absorption of vanadium from the gastrointestinal tract is poor, not exceeding 2% in humans. Soluble compounds of vanadium are absorbed to a considerable extent after inhalation and concentrated in the lung, but available information is not adequate for a reliable estimation of dose-response relationships. Absorbed vanadium is widely distributed in the body. In animals the highest values are found in bone, kidney, liver, and spleen. Bone maintains essentially unchanged levels for several weeks. Low concentrations have been detected in brain and in animal placenta and testes. Urine is the dominating route of excretion of absorbed vanadium. Animal and human data indicate that excretion occurs in at least two phases. A three-compartment model for elimination is described in humans with half-times after intravenous injection of 1.2 hours, 26 hours, and 10-12 days. Vanadium is essential for certain bacteria and microorganisms. Some reports suggest that vanadium is essential for mammals, but no biochemical function has been defined in humans. The total dietary intake is estimated to be 6-30 and in some regions up to 50 mu g/day. The use of vanadium salts as a supplement in athletes and body builders has been reported. Local effects in experimental animals are mainly seen in the respiratory tract. They may be acute and chronic, including bronchitis and pneumonia. Systemic effects have been observed in liver, kidney, nervous system, cardiovascular system, and blood-forming organs. Metabolic effects include interference with the biosynthesis of cystine and cholesterol, depression and stimulation of phospholipid synthesis and, at higher concentrations, inhibition of serotonin oxidation. Vanadate has been shown to inhibit Na+-K+-ATPase, phosphatases and several other enzyme systems. Vanadium compounds enhance the effects of insulin and have been shown to lower blood glucose in animal and human experiments in diabetic individuals. Both acute and chronic effects of occupational exposure to vanadium pentoxide (V2O5) and other vanadium compounds have been described. They are manifested mainly as delayed, but reversible irritation of the respiratory tract involving excess mucus production and prolonged coughing, accompanied by bronchospasm, wheezing, and diarrhea in cases of more severe exposure. Eye irritation and conjunctivitis have been reported in workers. Tracheobronchitis may result from heavy, long-term exposure. Changes in lung function indicating obstruction and an increase in inflammatory biomarkers have been demonstrated in boiler cleaners after prolonged exposure. Vanadium is not mutagenic in Ames test. However, pentavalent and tetravalent vanadium compounds have produced aneuploidy in somatic cells in vitro and in vivo. A clear evidence of carcinogenic activity has been shown in mice after inhalation of vanadium pentoxide. The International Agency for Research on Cancer (IARC) has classified vanadium as a possible carcinogen (Group 2B). Biological monitoring of vanadium in serum, blood, and urine is used to follow exposure to vanadium compounds in occupational and population studies. Urine analysis, being a noninvasive method, is suitable for monitoring of workers. Reviews on environmental, toxicological and occupational health aspects of vanadium have been published by IPCS (1988), ATSDR (1992), Domingo (1996), WHO (1996), IPCS (2001), Barceloux (1999), HSE (2002), and EFSA (2004).

  • 12. Lei, Li-Jian
    et al.
    Chen, Liang
    Jin, Tai-Yi
    Nordberg, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Chang, Xiu-Li
    Estimation of benchmark dose for pancreatic damage in cadmium-exposed smelters2007Inngår i: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 97, nr 1, 189-195 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to estimate the benchmark dose (BMD) for pancreas dysfunction caused by cadmium (Cd) exposure in smelters. Smelter workers who had been exposed to Cd for more than 1 year and matching nonoccupationally exposed subjects were asked to participate in this study. Urinary cadmium (UCd) was used as a biomarker for exposure, serum insulin and amylase were used as biomarkers for pancreatic effects. In this study, serum insulin and amylase were lower in the smelter workers than in the nonoccupationally exposed subjects. A significant dose-response relationship with UCd was displayed. BMI)s in terms of urinary Cd corrected for creatinine were calculated by use of BMDS (version 1.3.2). The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that the BMDL10 for serum insulin and serum amylase was 3.7 and 5.3 mu g/g Cr, respectively. Compared to the BMDL for renal damage caused by Cd exposure, identified by the effect biomarkers urinary beta(2)-microglobulin, urinary N-acetyl-beta-glucosaminidase, and urinary albumin (UALB), it was shown that BMDL10 for serum insulin is the lowest among all values and UALB gave the highest value (5.8 mu g/g Cr). This study indicates that Cd exposure can result in pancreatic dysfunction and the effect appears at lower urinary Cd level than renal dysfunction. The endocrine function of the pancreas was affected at lower urinary levels of Cd, compared to the exocrine function, which was seen at higher urinary levels of Cd than those giving rise to renal tubular dysfunction.

  • 13.
    Lundström, Ronnie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin. Arbetarskyddsstyrelsen, Forsknigsavdelningen, Tekniska enheten, Umeå.
    Vibration exposure of the glabrous skin of the human hand1985Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    An occupational exposure to hand-arm vibration can cause a complex of neurological, vascular and musculo-skeletal disturbances, known as the 'vibration syndrome'. However, the underlying pathophysiological mechanisms are not at all clear. Early signs of an incipient vibration syndrome are often intermittent disturbances in the cutaneous sensibility of the fingers, i.e. numbness and/or tactile paresthesias. At later stages, a vasoconstrictive phenomenon appears, usually as episodes of finger blanching.

    When using a vibratory tool, all mechanical energy entering the body has to be transmitted through, or absorbed by, the glabrous skin in contact with the handle. Therefore, the aims of this study was to investigate: (i) mechanical

    responses of the skin to vibrations, (ii) the response properties of cutaneous mechanoreceptors to vibrations, and (iii) influences of vibration exposure on touch perception.

    It was found by measuring the mechanical point impedance (0.02-10 kHz) that the skin is easy to make vibrate within the range of 80 to 200 Hz. Within or close to this range are the dominant frequencies of many vibratory tools. Thus, strong mechanical loads, such as compressive and/or tensile strain, can appear in the skin which, in turn, may induce temporary or permanent injuries.

    Recordings of impulses in single mechanoreceptive afferents, while the skin as exposed to vibrations, were obtained using needle electrodes inserted into the median nerve. The 4 types of mechanoreceptive afferents (FA I, FA II, SA I, and SA II) in the glabrous skin exhibited different response characteristics to vibrations. The FA I units were most easily excited at vibratory frequencies between ca 8 and 64 Hz and the FA II units between ca 64 and 400 Hz. The SA units were most sensitive at lower frequencies. At high stimulus amplitudes, such as may occur while using vibratory tools, a considerable overlap existed between the frequency ranges at which the units were exited. Evidence was also provided, that mechanical skin stimuli produced by edges of a vibrating object, compared to flat surfaces, more vigorously excited the FA I and particularly the SA I units. Thus, a marked edge enhancement, essential for tactile gnosis and precision manipulation, seems to exist already within the peripheral nervous system.

    Acure impairment of tactile sensibility caused by vibrations, proved to be due to a reduced sensitivity of the mechanoreceptive afferents. A loss of manual dexterity a*vi an increased risk for accidents may therefore appear, both during and after a vibration exposure.

    Percussive tools, high speed drills and ultrasonic devices are known to generate mechanical energy at frequencies above 1 kHz, i.e. frequencies usually not felt. At these frequencies, it is known that most of the energy, entering the body, is absorbed by the skin. Therefore, it was investigated whether a long-term exposure to high-frequency vibration may have a detrimental effect on the cutaneous sensitivity. One group of dentists and one of therapists, professionally exposed to high-frequency vibrations, were studied with regard to vibrotactile thresholds in their hands. The study showed that deleterious effects on tactile sensibility, at local exposure to high frequency vibration, can not be excluded.

  • 14.
    Nordberg, Gunnar F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Fowler, Bruce A.
    Risk Assessment2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 281-301 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Risk assessment for metallic substances usually follows the generally accepted framework format for risk assessment for all toxic substances, which involves (1) exposure assessment, (2) hazard identification, (3) assessment of dose-response relationships, and (4) risk characterization. The importance of risk communication is also addressed. Risk assessment/risk communication is of particular relevance for metals and metalloids, because all living organisms are exposed to these elements, and metals such as lead, cadmium, and mercury and the metalloid arsenic have been responsible for many human poisonings and even deaths. It is, hence, imperative that readers of this handbook have a firm perspective on the exposure levels of metallic substances that produce adverse health effects and the various risk assessment approaches that have been used and are evolving to protect the health and well-being of living organisms. Biomonitoring approaches, identification of toxic metallic species for hazard identification, dose-effect relationships, construction of dose-response curves, and the development of benchmark doses for various metallic species are discussed in relation to protecting sensitive subpopulations, because not all individuals within a general population are at equal risk for toxicity. Risk characterization using modern biomarkers that are capable of detecting early cellular effects to low-dose exposures to metallic substances will play an increasingly important role in assessing risk from exposure to this class of toxic substances on an individual or mixture basis. The issue of metal/metalloid-induced carcinogenesis is of ever increasing importance, because many of the elements associated with this cellular outcome produce a number of early cellular effects, including formation of reactive oxygen species (ROS) and apoptosis. Finally, the issue of risk communication/risk management is of great importance, because these issues are critical to addressing the health concerns of exposed populations and the practical, ethical, and financial issues related to reducing hazardous exposures to metallic substances.

  • 15.
    Nordberg, Gunnar F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Fowler, Bruce A.
    Nordberg, Monica
    Preface2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, V-V s.Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 16.
    Nordberg, Gunnar F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Fowler, Bruce ANordberg, MonicaFriberg, Lars T
    Handbook on the toxicology of metals2007Collection/Antologi (Annet vitenskapelig)
    Abstract [en]

    Handbook of the Toxicology of Metals is the standard reference work for physicians, toxicologists and engineers in the field of environmental and occupational health. This new edition is a comprehensive review of the effects on biological systems from metallic elements and their compounds. An entirely new structure and illustrations represent the vast array of advancements made since the last edition. Special emphasis has been placed on the toxic effects in humans with chapters on the diagnosis, treatment and prevention of metal poisoning. This up-to-date reference provides easy access to a broad range of basic toxicological data and also gives a general introduction to the toxicology of metallic compounds.

  • 17.
    Nordberg, Gunnar F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Fowler, Bruce A.
    Nordberg, Monica
    Friberg, Lars T.
    Introduction-General Considerations and International Perspectives2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 1-9 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    This introductory chapter is composed of two parts. The first section is a brief history of the science of the toxicology of metals by the late Dr. Lars Friberg. He delineates the early realization of the need for international cooperation and consensus that have guided seminal studies related to environmental and occupational toxicology. In this spirit, he initiated work on the first edition of the Handbook of Toxicology of Metals that included contributors from around the world. The second section takes up some current concerns related to the toxicology of metals. It highlights such concerns in relation to the current status of the scientific understanding to date of the metals included and discussed fully in the chapters of the Handbook. Furthermore, it draws attention to future directions in generating new knowledge to fill gaps in the continued quest to assemble the knowledge base necessary for the protection of human health from adverse consequences related to exposure to metals.

  • 18.
    Nordberg, Gunnar F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Gerhardsson, Lars
    Broberg, Karin
    Mumtaz, Moiz
    Ruiz, Patricia
    Fowler, Bruce A.
    Interactions in Metal Toxicology2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 117-145 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Human exposures to metals and metalloids such as arsenic frequently occur as mixtures, and hence it is important to consider interactions among these elements in terms of both mechanisms of action and for risk assessment purposes. Interactions among these elements may produce additive, synergistic/potentiative, or antagonistic effects that may be manifested as direct cellular toxicity (necrosis or apoptosis) or carcinogenicity. Dose-response relationships may further be influenced by constitutive factors such as age, sex, and the expression of specific proteins. The roles of molecular factors regulated by specific genes (so called gene-environment interactions) for the expression of metal toxicity are known only to a limited extent for most metals. However, for chronic beryllium disease causing fibrosis of the lung, it has been shown that beryllium sensitization, a prerequisite for developing the disease, depends on an antigen-specific immune response occurring predominantly among persons with a specific HLA-DBP1 genotype. Some gene-environment interactions in terms of genetic polymorphisms have been demonstrated such as those involving ALAD and arsenic methyl transferases, but the importance of these observations for development of human diseases has not been fully explored. Mechanisms of importance for interactions and the development of toxicity are the expression of metal-binding proteins (metallothioneins or lead-binding proteins). In many cases, direct primary data on interactions among toxic or essential elements are lacking, and so innovative derivative methods such as the binary weight of evidence (BINWOE) method have been used to predict potential interactions among groups of metals and metalloids. At present, there is much to be learned about interactions among both toxic and essential elements, but this is clearly a critical area of research.

  • 19.
    Nordberg, Gunnar F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Nogawa, Koji
    Friberg, Lars T.
    Nordberg, Monica
    Cadmium2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 445-486 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Cadmium (Cd) is chemically similar to zinc; it occurs naturally with zinc and lead in sulfide ores. Elevated concentrations in air, water, and soil may occur close to industrial emission sources, particularly those of nonferrous mining and metal refining industries. Cadmium metal has been used as an anticorrosive, electroplated onto steel, and Cd compounds are used as pigments, often in plastics. Cadmium and its compounds are also used in electric batteries, electronic components, and nuclear reactors. Because some of the applications of Cd can be performed by other less-toxic materials, the use of Cd has, therefore, been restricted by law in some countries. The absorption of Cd compounds through the skin is negligible. Between 10 and 50% of inhaled Cd will be absorbed, with the degree of absorption being greater for smaller particles and fumes than for larger dust particles. Humans absorb 5-10% of ingested Cd. A low intake of calcium, zinc, or iron increases the degree of absorption; for example, in iron-deficient individuals, the gastrointestinal absorption rate may be as high as 20%. Cadmium is transported in plasma when bound to metallothionein-a low-molecular-weight protein and/or to certain high-molecular-weight proteins. The accumulation of Cd occurs in many tissues, with particularly long half-lives (10-30 years) having been reported for Cd in muscle, kidney, and liver tissue. Cadmium stimulates metallothionein production in the same manner as other bivalent metals, such as zinc, copper, and mercury. Metallothionein-bound Cd in plasma is filtered through the renal glomeruli and reabsorbed in the tubuli, where the metal ion is released after lysosomal degradation of the protein. The unbound Cd stimulates the production of new metallothionein, which binds the Cd in the renal tubular cells. When not all of this new Cd is bound, toxic effects occur, possibly because of the interference of Cd with zinc-dependent enzymes and/or membrane function. The average amount of Cd ingested in most European and North American countries is approximately 1020 mu g/day. The corresponding average urinary excretion is approximately 0.5-1.0 mu g/day. Most of the Cd in blood is located in the cells. The average blood concentration is approximately 0.5-1.0 mu g/L in nonsmokers; it is twice as high in smokers because of Cd absorption from cigarette smoke. Concentrations of 10-20 mu g/kg are usually found in the kidney cortex of nonsmokers in European countries. Although the intake of Cd through food has been higher in Japan than in Europe, and the reported tissue levels are correspondingly higher, the food intake of Cd has decreased in Japan during the last few decades. Ingestion of highly contaminated food or drink results in acute gastrointestinal effects with concomitant diarrhea and vomiting. Acute inhalation of Cd in air-for example, from soldering or welding fumes-may lead to severe chemical pneumonitis. Long-term exposure to low air levels may lead to chronic obstructive lung disease and possibly lung cancer. Long-term excessive exposure from the air or food leads to renal tubular dysfunction. The first sign of damage is a low-molecular-weight proteinuria. This condition is the critical effect of such exposure to Cd and is used in quantitative risk assessment. Long-term exposure from food, often combined with other means of delivery, may also lead to disturbance of calcium metabolism, osteoporosis, and osteomalacia, mainly among postmenopausal women. A disease exhibiting these features-called Itai-Itai disease-occurred in the 1950s in Cd-polluted areas of Japan; 124 cases were diagnosed up to 1970, and decreasing numbers of clinical cases have been diagnosed later, with 66 cases during the period between 1970 and 2006. In animals exposed to Cd through injection, inhalation, or oral exposure, cancer may develop at the injection site, in the lungs and prostate, or in other organs. Although some epidemiological studies have found an increase in the rates of cancer of the lungs and prostate, other studies have not demonstrated such effects. Cadmium is classified as a human carcinogen (Group 1) by the International Agency for Research on Cancer. Exposure to Cd in the air at concentrations of 5-10 mu g/m(3) during a working life of 45 years may give rise to renal tubular dysfunction in a small proportion of exposed workers. At approximately 100 mu g/m(3), signs of chronic obstructive lung disease may develop even after exposure for a shorter duration. After a lifetime of exposure from food at an average intake of approximately 200 mu g/day, renal effects have been observed at age 50. There is considerable individual variation in the sensitivity of these renal effects. It has been suggested that such effects can be avoided if renal cortex levels are kept <50 mu g/kg and urine levels <2.5 mu g/g CR. Recent reports of low, but statistically significant, increases at even lower levels of urinary Cd are, however, noteworthy. Such increases are observed in the general population, particularly among people with diabetes. There is no specific treatment for Cd poisoning. When there are signs of osteomalacia, large doses of vitamin D should be given. Because of the long half-life of Cd in the kidneys, which are the critical organs and the irreversibility of the critical effect, primary prevention is essential. Prevention can be assisted through environmental and biological monitoring. The extensive literature on the toxicological and environmental aspects of Cd has been reviewed in detail by Friberg et al. (1974, 1985, 1986a), Tsuchiya (1978), Nriagu (1980, 1981), the WHO/IPCS (1992), the IARC (1993), Jarup et al. (1998c), the ATSDR (1999), Nordberg and Nordberg (2002), the EU (2003), Satarug and Moore (2004), and the WHO/FAO (2003, 2005).

  • 20.
    Sandström, Monica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin. National Institute for Occupational Health, Umeå, Sweden.
    Hansson Mild, Kjell
    National Institute of Occupational Health, Umeå, Sweden.
    Stenberg, Berndt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Dermatologi och venereologi.
    Wall, Stig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Skin symptoms among VDT workers and electromagnetic-fields: a case-referent study1995Inngår i: Indoor Air, ISSN 0905-6947, E-ISSN 1600-0668, Vol. 5, nr 1, 29-37 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Th is case referent study is a part of the Office illness Project in Northern Sweden. From a questionnaire study among 5986 office workers, 75 VDT workers with self-reported facial skin symptoms and the same number of referents were selected for this study. The environmental electric and magnetic fields in the office as well as electromagnetic fields associated with the VDT at the workplace were measured, The aim of this part of the project was to explore the role of the measured electromagnetic parameters in relation to skin symptoms. For most of the measured parameters there was no difference between cases and referents. However, more cases than referents were found in the highest exposure group for two of the measured parameters. Fm the background electric field in the mom the relative risk in terms of crude odds ratio (OR) was 3.0 (95% CI: 1.2-7.2) for the high exposed group (greater than or equal to 31 V/m) compared with the lowest group (less than or equal to 10 V/m). The same comparison for the magnetic field in the ELF-range (greater than or equal to 0.30 mu T vs less than or equal to 0.145 mu T) in front of the VDT gave an OR of 2.7(95% CI: 1.0-6.9).

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