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  • 1. Aggett, Peter
    et al.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Monica
    Essential metals: assessing risks from dificiency and toxicity2015Inngår i: Handbook on the toxicology of metals: Volume I: General considerations / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg, Academic Press, 2015, 4, s. 281-297Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Recommendations aimed at protecting the public from toxicity of essential elements including essential metals 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 a 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 intake (AROI), in which no adverse effects occur. It must be noted, however, that 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. The AROI is defined as protecting 95% of an unselected human population from minimal adverse effects of deficiency or toxicity.

  • 2. 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, s. 65-78Kapittel 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.

  • 3. Akesson, Agneta
    et al.
    Barregard, Lars
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Monica
    Skerfving, Staffan
    Non-Renal Effects and the Risk Assessment of Environmental Cadmium Exposure2014Inngår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 122, nr 5, s. 431-438Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure. Objectives: Our objective was to review available information on health effects of Cd exposure with respect to human health risk assessment. Discussion: The associations between U-Cd and urinary proteins at very low exposure may not be due to Cd toxicity, and the clinical significance of slight proteinuria may also be limited. More importantly, other effects have been reported at very low Cd exposure. There is reason to challenge the basis of the existing health risk assessment for Cd. Our review of the literature found that exposure to low concentrations of Cd is associated with effects on bone, including increased risk of osteoporosis and fractures, and that this observation has implications for the health risk assessment of Cd. Other effects associated with Cd should also be considered, in particular cancer, although the information is still too limited for appropriate use in quantitative risk assessment. Conclusion: Non-renal effects should be considered critical effects in the health risk assessment of Cd.

  • 4.
    Andersson, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN studies, Luleå, Sweden..
    Backman, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN studies, Luleå, Sweden.
    Nordberg, Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hagenbjörk, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN studies, Luleå, Sweden.
    Eriksson, Kåre
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN studies, Luleå, Sweden.
    Early life swimming pool exposure and asthma onset in children: a case-control study2018Inngår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 17, artikkel-id 34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Trichloramine exposure in indoor swimming pools has been suggested to cause asthma in children. We aimed to investigate the risk of asthma onset among children in relation to individual trichloramine exposure.

    METHODS: A longitudinal nested case-control study of 337 children with asthma (cases) and 633 controls aged 16-17 years was performed within a population-based cohort from The Obstructive Lung Disease in Northern Sweden studies (OLIN). Year of asthma onset and exposure time at different ages were obtained in telephone interviews. Trichloramine concentrations in the pool buildings were measured. Skin prick test results for inhalant allergens were available from previous examinations of the cohort. The risk for asthma was analyzed in relation to the cumulative trichloramine exposure before onset of asthma.

    RESULTS: Swimming pool exposure in early life was associated with a significantly higher risk of pre-school asthma onset. A dose-response relationship between swimming pool exposure and asthma was indicated in children with asthma onset at 1 year of age. Children who were both sensitized and exposed had a particularly high risk.

    CONCLUSIONS: Early life exposure to chlorinated swimming pool environments was associated with pre-school asthma onset.

  • 5.
    Andersson, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Hedman, Linnéa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Nordberg, Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eriksson, Kåre
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Swimming pool attendance is related to asthma among atopic school children: a population-based study2015Inngår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 14, nr 14, artikkel-id 37Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: By-products of water disinfectants have been suggested to cause asthma, especially in atopic children. However, studies on indoor swimming pool attendance and asthma in children have presented conflicting results. The present study examined the relationship between indoor swimming pool attendance and asthma among sensitized and non-sensitized children aged 11-12 years.

    Methods: An extended ISAAC questionnaire was sent to the families of all children attending fifth or sixth grade, aged 11-12 years, in two municipalities in Northern Sweden in 2010. A total of 1866 participated (96% of those invited) in the questionnaire study and 1652 (89%) also participated in skin prick testing for 10 standard airborne allergens. Asthma was defined as physician-diagnosed asthma in combination with wheeze or use of asthma medication in the last 12 months. Current swimming pool attendance was reported as >= 1/week or <1/week. Logistic regression models were used for data analysis.

    Results: The prevalence of current asthma was 8.9% (10.0% of boys; 7.9% of girls) and 14% had attended indoor pools >= 1/week. Children currently attending swimming pools >= 1/week had an increased risk of current asthma. Stratified analyses for allergic sensitization adjusted for sex, parental smoking, parental asthma, and damp housing, showed a statistically significant association for current asthma only among sensitized subjects (OR 95% CI 1.90 1.09-3.32). No association was found between current pool attendance and wheeze, sensitization, rhinitis or eczema.

    Conclusions: The present study supports the proposed link between indoor swimming pool attendance and asthma in sensitized children.

  • 6. 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, s. 39-64Kapittel 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.

  • 7. 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, s. 163-176Kapittel 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.

  • 8. Chen, Liang
    et al.
    Jin, Taiyi
    Huang, Bo
    Chang, Xiuli
    Lei, Lijian
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Monica
    Plasma metallothionein antibody and cadmium-induced renal dysfunction in an occupational population in China.2006Inngår i: Toxicol Sci, ISSN 1096-6080, Vol. 91, nr 1, s. 104-12Artikkel i tidsskrift (Fagfellevurdert)
  • 9. Chen, Liang
    et al.
    Jin, Taiyi
    Huang, Bo
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Monica
    Critical exposure level of cadmium for elevated urinary metallothionein--an occupational population study in China.2006Inngår i: Toxicol Appl Pharmacol, ISSN 0041-008X, Vol. 215, nr 1, s. 93-9Artikkel i tidsskrift (Fagfellevurdert)
  • 10. Chen, Liang
    et al.
    Lei, Lijian
    Jin, Taiyi
    Nordberg, Monica
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Plasma metallothionein antibody, urinary cadmium, and renal dysfunction in a Chinese type 2 diabetic population.2006Inngår i: Diabetes Care, ISSN 0149-5992, Vol. 29, nr 12, s. 2682-7Artikkel i tidsskrift (Fagfellevurdert)
  • 11. Chen, Xiao
    et al.
    Wang, Zhongqiu
    Zhu, Guoying
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ding, Xiaoqiang
    Jin, Taiyi
    The association between renal tubular dysfunction and zinc level in a Chinese population environmentally exposed to cadmium2018Inngår i: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 186, nr 1, s. 114-121Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Microglobulin (UBMG) were measured. The median UCd, BCd, SZn, and HZn were 2.8 and 13.6 μg/g cr, 1.3 and 12.2 μg/L, 1.31 and 1.12 mg/L, and 0.14 and 0.12 mg/g in subjects living in control and polluted areas. The UBMG level of subjects living in the polluted area was significantly higher than that of the control (0.27 vs 0.11 mg/g cr, p < 0.01). SZn, HZn, and Zn/Cd ratios were negatively correlated with UBMG (p < 0.05 or 0.01). Subjects with high SZn concentrations (≥ 1.62 mg/L) had reduced risks of elevated UBMG [(odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.07-0.99)] after controlling for multiple covariates compared with those with lower zinc levels. A similar result was observed in subjects with high HZn (OR = 0.09, 95% CI 0.02-0.48). The ORs of the second, third, and fourth quartiles of Zn/Cd ratio were 0.40 (95% CI 0.19-0.84), 0.14 (95% CI 0.06-0.37), and 0.01 (95% CI 0.02-0.18) for renal dysfunction compared with those of the first quartile, respectively. For those subjects with high level of UCd, high level of SZn and HZn also had reduced risks of elevated UBMG. The results of the present study show that high zinc body burden is associated with a decrease risk of renal tubular dysfunction induced by cadmium. Zinc nutritional status should be considered in evaluating cadmium-induced renal damage.

  • 12. Chen, Xiao
    et al.
    Wang, Zhongqiu
    Zhu, Guoying
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Jin, Taiyi
    Ding, Xiaoqiang
    The association between cumulative cadmium intake and osteoporosis and risk of fracture in a Chinese population2019Inngår i: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 29, nr 3, s. 435-443Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bone is one of the target organs for cadmium toxicity. However, few studies have shown the association between cumulative cadmium intake and prevalence of osteoporosis and bone fracture. In the present study, we evaluated the association between cumulative cadmium intake and osteoporosis and risk of fracture in a Chinese population. A total of 790 subjects (488 women and 302 men) living in a control area and two cadmium-polluted areas were included. The cumulative cadmium intake was estimated by a food survey. The bone mineral density was determined by using single-photon absorptiometry. The cumulative cadmium intakes were 0.48, 2.14, and 11.00 g for men, and 0.42, 2.11, and 11.12 g in women in control, and moderately and heavily polluted areas, respectively. In women, the odds ratios (ORs) of subjects with a cadmium intake between 2.21 and 10.63 g and >10.63 g were 1.30 (95% CI: 0.58-2.94) and 2.36 (95% CI: 1.14-5.16), compared with those with a cadmium intake < 0.58 g after adjusting to the confounders for osteoporosis. The ORs of subjects with a cadmium intake >10.63 g were 2.34 (95% CI: 1.23-4.38) for all of the women and 2.62 (95% CI: 1.02-5.58) in women ≥ 60 years old, compared with those with a cadmium intake <10.63 g after adjusting to the confounders for bone fractures. In men, similar trends were observed, but no statistical significance was found. In addition, those subjects with renal tubular dysfunction showed high risk of bone fracture. Our results indicate that a high level of cumulative cadmium intake is associated with an increased rate of osteoporosis and fractures among women.

  • 13. Chen, Xiao
    et al.
    Zhu, Guoying
    Wang, Zhongqiu
    Liang, Yihuai
    Chen, Bo
    He, Ping
    Nordberg, Monica
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nordberg, Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ding, Xiaoqiang
    Jin, Taiyi
    The association between dietary cadmium exposure and renal dysfunction - the benchmark dose estimation of reference levels: the ChinaCad study2018Inngår i: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 38, nr 10, s. 1365-1373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25gkg(-1) body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey. Blood cadmium, urinary cadmium and renal function markers (microalbuminuria, N-acetyl--d-glucosaminidase [NAG] and its isoform B [NAGB], (2)-microglobulin and retinol binding protein) in urine were measured. We calculated the 95% lower confidence bounds of BMD (BMDLs) of cumulative cadmium intake. In control and two polluted areas, the median cumulative cadmium intake was 0.5, 2.1 and 11.1g. The odds ratio of the intermediate (1.0-3.0g), second highest (3.0-11.0g) and the highest cumulative cadmium intake (>11.0g) compared with the lowest cumulative cadmium intake (<1.0g) were 2.8 (95% CI: 1.4-5.8), 8.1 (95% CI: 3.8-17.2) and 11.4 (95% CI: 6.5-26.4) for urinary NAG and 6.6 (95% CI: 3.2-13.8), 14.8 (95% CI: 6.8-32.2) and 22.5 (95% CI: 10.7-47.5) for urinary NAGB. The BMDLs of cumulative cadmium intake were 1.1-1.2g (benchmark response [BMR]=5%) for urinary NAG, and were 0.7-0.9g (BMR=5%) for urinary NAGB, and were 1.3-1.4g (BMR=5%) for urinary (2)-microglobulin. The BMDLs of cumulative cadmium intake in a Chinese population were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection. Several studies indicated that the tolerable dietary intake of cadmium should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using benchmark dose (BMD) approach. The lowest BMD lower bound confidence limits of cumulative cadmium intake were 0.7-0.9g (benchmark response=5%). The BMD lower bound confidence limits of cumulative cadmium intake were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection.

  • 14. Elder, Alison
    et al.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Kleinman, Michael
    Routes of exposure, dose, and toxicokinetics of metals2015Inngår i: Handbook on the toxicology of metals: Volume I: General considerations / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg, Academic Press, 2015, 4, s. 45-74Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The chapter first describes the main sources of metal 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 on the lung, the absorption of metal in the gastrointestinal tract is less well understood. A summary diagram shows the contribution of all the absorption processes to the total body burden. Since the publication of the third 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 via 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 via the sulfate carrier. Attention is also given to the transport of ultrafine particles and nanoparticles across barrier epithelia. The fecal excretion of several metals occurs as the end result of extensive enterohepatic recirculation. In the case of certain organometallic species, gut microflora may play a critical role in converting the metal to an inorganic form, which is excreted in the feces. Renal accumulation and excretion of metals has also received considerable attention. Renal accumulation of cadmium in the form of its complex with the small molecular weight protein, metallothionein, 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 observation-based models, pharmacokinetic models can be developed based on a priori physiological and mechanistic considerations. The chapter concludes with a consideration of indicator media that best reflect the dose to the critical organ.

  • 15. Elinder, Carl-Gustaf
    et al.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Re: Byber et al. in Critical Reviews in Toxicology 2016;46:191-2402017Inngår i: Critical reviews in toxicology, ISSN 1040-8444, E-ISSN 1547-6898, Vol. 47, nr 10, s. 904-905Artikkel i tidsskrift (Fagfellevurdert)
  • 16. Gerhardsson, Lars
    et al.
    Akantis, Anna
    Lundström, Nils-Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Schütz, Andrejs
    Skerfving, Staffan
    Lead concentrations in cortical and trabecular bones in deceased smelter workers.2005Inngår i: J Trace Elem Med Biol, ISSN 0946-672X, Vol. 19, nr 2-3, s. 209-15Artikkel i tidsskrift (Fagfellevurdert)
  • 17.
    Gunnarsson, David
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Lundgren, Per
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap.
    Selstam, Gunnar
    Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten).
    Cadmium-induced decrement of the LH receptor expression and cAMP levels in the testis of rats2003Inngår i: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 183, nr (1-3), s. 57-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cadmium (Cd) is a widespread environmental pollutant, characterized by its ability to affect various organs. Adverse effect of Cd on the testis including decreased testosterone production are well-known phenomena, but the cellular events explaining these effects have not yet been established. In the present study the initial steps of gonadotropin mediated testosterone biosynthesis were examined in vivo in rats, in relation to Cd dose and time after injection. In the dose–response experiment Male Sprague–Dawley rats received a single subcutaneous (sc) injection of CdCl2 (1, 5 or 10 μmol/kg body weight) and were sacrificed 48 h after injection. A statistically significant decrease in luteinizing hormone (LH) receptor mRNA level in the testicular tissue was demonstrated at the highest dose (10 μmol/kg). In the temporal–response experiment rats were given 10 μmol/kg of CdCl2 sc and sacrificed 0.48, 4.8, 48 or 144 h after injection. LH receptor mRNA levels as well as cyclic adenosine monophosphate (cAMP) levels were found to be significantly lowered at 48 and 144 h. These observations of the mechanisms whereby Cd exerts its effect on the initial steps of testosterone biosynthesis are the first from in vivo experiments.

  • 18.
    Gunnarsson, David
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Selstam, Gunnar
    Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten).
    Differential effects of cadmium on the gene expression of seven-transmembrane-spanning receptors and GAPDH in the rat testis.2007Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 168, nr 1, s. 51-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cadmium (Cd) is a widely spread toxicant with endocrine disrupting properties. Under experimental conditions it suppresses sex steroid synthesis in the male as well as the female. Testicular steroidogenesis is primarily regulated by gonadotropins, but is also influenced by catecholamines. We have previously shown that Cd exposure affects rat testosterone synthesis by down-regulating luteinizing hormone (LH) receptor mRNA expression. In this study, rats were given 10 micromol/kg Cd subcutaneously and sacrificed 0.48-144 h later. We investigated the effects of Cd on testicular gene expression of two adrenergic receptors. In addition, mRNA levels of the androgen-regulated house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were measured. In contrast to the suppressive influence on LH receptor expression Cd lacked effect on the expression of alpha(1A)- and beta(2)-adrenergic receptors. GAPDH gene expression, on the other hand, was up-regulated 1.6-fold after exposure to 10 micromol/kg Cd. These data suggest that the influence of Cd on testicular gene expression involves a specific effect on the LH receptor and not a general effect on seven-transmembrane-spanning receptors. Also, data indicate that the increased expression of GAPDH may be secondary to Cd-induced testosterone deprivation, suggesting future studies of androgen-regulated genes in the toxicity of Cd.

  • 19.
    Gunnarsson, David
    et al.
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Svensson, Mona
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Selstam, Gunnar
    Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten).
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Pronounced induction of testicular PGF2alpha and suppression of testosterone by cadmium: prevention by zinc2004Inngår i: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 200, nr 1, s. 49-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In order to investigate the effects of cadmium (Cd) on testicular prostaglandin F(PGF) production, adult male Sprague–Dawley rats were exposed to CdCl2 by subcutaneous injections. Dose–response as well as temporal–response experiments were performed, and PGF levels were determined by radioimmunoassay (RIA). The highest cadmium dose (10 μmol/kg) caused a dramatic elevation of testicular PGF, which was established to occur 48 h after exposure. At this point of time, cadmium-treated animals displayed PGF levels 16.7 times higher than saline-injected controls. No significant differences were found with the lower doses used (1 and 5 μmol/kg). In addition, the influence of pre-treatment with zinc (Zn) was assessed. The very strong stimulatory effect on PGF synthesis (22.3-fold) detected after exposure to 20 μmol/kg cadmium, was completely absent in the group given zinc (1 mmol/kg) prior to cadmium exposure. Plasma testosterone concentrations were determined in the three experiments, and all groups with strongly elevated PGF levels showed drastically lowered concentrations of testosterone. Zinc pre-treatment abolished not only the cadmium-induced rise in PGF but also the testosterone reduction. Additionally, cadmium was found to inhibit the expression of steroidogenic acute regulatory protein (StAR), which is responsible for the rate-limiting step in steroidogenesis. The present findings establish that cadmium can cause a strong induction of testicular PGF production, which might help to explain the well-known antisteroidogenic effect of this heavy metal. Such an inhibitory effect could be due to reduced levels of StAR.

  • 20.
    Helleday, Ragnberth
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Segerstedt, Bo
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Forsberg, Bertil
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Mudway, Ian
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bernard, Alfred
    Blomberg, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Exploring the time dependence of serum clara cell protein as a biomarker of pulmonary injury in humans.2006Inngår i: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 130, nr 3, s. 672-675Artikkel i tidsskrift (Fagfellevurdert)
  • 21. Holler, James S
    et al.
    Fowler, Bruce A
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Silver2015Inngår i: Handbook on the toxicology of metals: Volume II: Specific metals / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg, Academic Press, 2015, 4, s. 1209-1216Kapittel i bok, del av antologi (Fagfellevurdert)
    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. After ingestion in humans, the highest concentrations of silver are usually found in the liver and spleen, but also to some extent in the muscles, skin, and brain. 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 humans. Silver binds to high molecular weight proteins and metallothionein in tissue cytosol fractions. Excretion of silver from the body is primarily biliary. Silver nanoparticles have been shown to be absorbed by both inhalation and oral routes, resulting in deposition in various organ systems. 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 gray-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.

  • 22. 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, s. 809-814Kapittel 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.

  • 23. Iavicoli, Ivo
    et al.
    Fontana, Luca
    Nordberg, Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    The effects of nanoparticles on the renal system2016Inngår i: Critical reviews in toxicology, ISSN 1040-8444, E-ISSN 1547-6898, Vol. 46, nr 6, s. 490-560Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Through a process of translocation across biological barriers, nanoparticles can reach and deposit in secondary target organs where they may induce adverse biological reactions. Therefore, a correct assessment of nanoparticle-induced adverse effects should take into account the different aspects of toxicokinetics and tissues that may be targeted by nanoparticles. For this reason, a comprehensive evaluation of renal nanotoxicity is urgently needed as kidneys are particularly susceptible to xenobiotics and renal excretion is an expected and possible elimination route of nanoparticles in living organisms. On one hand, summarizing the findings of in vitro and in vivo studies that have investigated the adverse effects of nanoparticles on the kidney, this review intends to provide a thorough insight into the nephrotoxicity of these substances. The evaluation of the in vitro studies revealed that different types of nanoparticles (carbon, metal and/or silica nanoparticles) are able to exert significant cytotoxic effects (i.e., decreased cell viability, induction of oxidative stress, mitochondrial or cytoskeleton dysfunction and cell membrane and DNA damage). On the other hand, in vivo studies demonstrated that nanoparticles exhibited an important nephrotoxic potential both at tubular (i.e., degeneration of tubular epithelial cell, cellular fragments and proteinaceous liquid in tubule lumen, renal interstitial fibrosis) and glomerular level (i.e., swollen glomeruli, changes in Bowman's space and proliferation of mesangial cells). Although the data currently available indicate that nanoparticles may adversely impact the renal system, further studies are needed in order to clarify all the potential molecular mechanisms of nephrotoxicity induced by these xenobiotics, in particular at glomerular level.

  • 24. Jin, T.
    et al.
    Chen, L
    Lei, L.J
    Nordberg, M
    Nordberg, G.F
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Factors influencing dose-response relationships of cadmium in humans – diabetes, metalllothionein and metallothionein antibodies.2008Inngår i: Cell Biology and Toxicology, ISSN 0742-2091, E-ISSN 1573-6822, Vol. 24, nr 5, s. 451-55Artikkel i tidsskrift (Fagfellevurdert)
  • 25.
    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, s. 451-455Artikkel i tidsskrift (Fagfellevurdert)
  • 26. Jin, Taiyi
    et al.
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ye, Tingting
    Bo, Meihua
    Wang, Hongfu
    Zhu, Guoying
    Kong, Qinghu
    Bernard, Alfred
    Osteoporosis and renal dysfunction in a general population exposed to cadmium in China.2004Inngår i: Environ Res, ISSN 0013-9351, Vol. 96, nr 3, s. 353-9Artikkel i tidsskrift (Fagfellevurdert)
  • 27.
    Lagerkvist, Birgitta Json
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bernard, Alfred
    Blomberg, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Bergström, Erik
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Forsberg, Bertil
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Holmstrom, Karin
    Karp, Kjell
    Lundstrom, Nils-Goran
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Segerstedt, Bo
    Svensson, Mona
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Pulmonary epithelial integrity in children: relationship to ambient ozone exposure and swimming pool attendance.2004Inngår i: Environ Health Perspect, ISSN 0091-6765, Vol. 112, nr 17, s. 1768-71Artikkel i tidsskrift (Fagfellevurdert)
  • 28. Landrigan, Philip
    et al.
    Nordberg, Monica
    Lucchini, Roberto
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Grandjean, Philippe
    Iregren, Anders
    Alessio, Lorenzo
    The Declaration of Brescia on prevention of the neurotoxicity of metals.2007Inngår i: Am J Ind Med, ISSN 0271-3586, Vol. 50, nr 10, s. 709-11Artikkel i tidsskrift (Fagfellevurdert)
  • 29.
    Liang, Y
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Li, H
    Lei, L
    Yin, T
    Nordberg, M
    Nordberg, G
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Immunolocalization of metallothionein in liver and kidney of Wistar rats exposed to cadmium.2008Inngår i: Cell Biology and Toxicology, ISSN 0742-2091, E-ISSN 1573-6822, Vol. 24, nr 1, s. 95-6Artikkel i tidsskrift (Fagfellevurdert)
  • 30.
    Liang, Yihuai
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lei, Lijian
    Department of Occupational Health and Toxicology (Key Laboratory of Public Health Safety, Ministry of Education of China), School of Public Health, Fudan University, Shanghai, People’s Republic of China.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Li, Huiqi
    Department of Occupational Health and Toxicology (Key Laboratory of Public Health Safety, Ministry of Education of China), School of Public Health, Fudan University, Shanghai, People’s Republic of China.
    Nordberg, Monica
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bernard, Alfred
    Unit of Toxicology, Université catholique de Louvain, Brussels, Belgium.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bergdahl, Ingvar A
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jin, Taiyi
    Department of Occupational Health and Toxicology (Key Laboratory of Public Health Safety, Ministry of Education of China), School of Public Health, Fudan University, Shanghai, People’s Republic of China.
    Renal function after reduction in cadmium exposure: an eight-year follow-up of residents in cadmium-polluted areas2012Inngår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 120, nr 2, s. 223-228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and objective: Long-term exposure to cadmium (Cd) causes renal dysfunction, but its change with exposure is unknown. We aimed at assessing the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice.

    Methods: 412 residents in previously Cd-polluted and non-polluted areas were examined twice: in 1998 and 2006. Changes in blood Cd, urinary Cd, and kidney function (N-acetyl-β-D-glucosaminidase = NAG, β2-microglobulin, and albumin in urine) were measured. Results: In the most polluted area, mean blood Cd was 8.9 μg/L in 1998 and 3.3 μg/L in 2006, and urinary Cd was 11.6 and 9.0 μg/g creatinine in 1998 and 2006, respectively. Urinary albumin in 1998 increased with urinary Cd but no such exposure-response appeared for 2006 albumin versus urinary Cd 1998, indicating recovery. Other biomarkers of kidney function were also elevated in 1998. Partial recovery was observed for NAG, among women, and suggested for β2-microglobulin, among young individuals. The probability of having a β2-microglobulin above the 95th percentile in 2006 was high in those with an elevated β2-microglobulin in 1998 (odds ratio: 24.8, 95% CI: 11.2-55.3), whereas corresponding estimates for albumin and NAG were 3.0 (1.2-7.5) and 2.6 (1.6-4.4), respectively.

    Conclusions: Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For the markers of tubular effects, a tendency towards improvement, but not complete recovery, was observed. Data from repeated observations suggests that β2-microglobulin may be more informative than NAG as an indicator for the individual's future tubular function.

  • 31.
    Liang, Yihuai
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Li, Huiqi
    Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, China.
    Xiang, Cuiqin
    Shanghai Municipal Center For Disease Control and Prevention, Shanghai, China.
    Lei, Lijian
    Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, China.
    Jin, Taiyi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Monica
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Increased hepatic and decreased urinary metallothionein in rats after cessation of oral cadmium exposure2010Inngår i: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 106, nr 4, s. 348-355Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated the role of metallothionein (MT) in tissues after cessation of cadmium (Cd) exposure. Wistar rats of both genders were given CdCl(2) in drinking water at daily doses of 0, 2.5, 5.0 or 10.0 mg Cd/kg body-weight for 12 weeks. Half of the animals were then killed; the others were given Cd-free water for the following 16 weeks, i.e. until 28 weeks after start of the experiment (28-week rats). We observed dose-dependent increases in the levels of MT in the tissues of rats 12 weeks after beginning the experiment (12-week rats). After the exposure ceased, levels of MT in the 28-week rats changed in three ways: an increase in the liver, persistence in the kidney cortex and a decrease in the medulla, relative to those levels in their 12-week counterparts. Biomarkers of kidney dysfunction were determined to be urinary MT (UMT) and urinary N-acetyl-beta-d-glucosaminidase (UNAG). After 12 weeks, we observed dose-related statistically significant increases in UMT and UNAG in all of the Cd-exposed groups. A statistically significant decrease for UNAG between the 12- and 28-week rats occurred among males at the lowest Cd dose and for UMT in all of the Cd-exposed groups. The unchanged tissue levels of MT in the kidney cortex suggest that decreased UMT is a sign either of (i) decreased transport of Cd-MT from the liver via blood plasma to the renal tubules or (ii) increased tubular reabsorption and recovery of renal tubular function.

  • 32. Lu, Jian
    et al.
    Jin, Taiyi
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Monica
    Metallothionein gene expression in peripheral lymphocytes and renal dysfunction in a population environmentally exposed to cadmium.2005Inngår i: Toxicol Appl Pharmacol, ISSN 0041-008X, Vol. 206, nr 2, s. 150-6Artikkel i tidsskrift (Fagfellevurdert)
  • 33.
    Lundström, Nils-Göran
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Yrkes- och miljömedicin.
    Englyst, Vagn
    Gerhardsson, Lars
    Jin, Taiyi
    Nordberg, Gunnar
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lung cancer development in primary smelter workers: a nested case-referent study.2006Inngår i: Journal of Occupational and Environmental Medicine, ISSN 1076-2752, E-ISSN 1536-5948, Vol. 48, nr 4, s. 376-380Artikkel i tidsskrift (Fagfellevurdert)
  • 34.
    Nordberg, G F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fowler, B A
    Nordberg, M
    Metal Exposures in Occupational and Environmental Settings2015Inngår i: International Commission on Occupational Health Newsletter, ISSN 1795-0260, Vol. 13, nr 1, s. 12-14Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The use of metals has expanded substantially in the last century and gives rise to widespread exposure of humans. It has long been recognized that metals are important toxic agents that may cause acute and chronic poisoning in metal workers and population groups with high exposures. In recent years evidence has been presented indicating that low level exposures to metallic compounds contribute to the occurrence of several common diseases. The World Health Organization (WHO, 2009) has estimated that on a Global basis, 143,000 deaths and nearly 9 million disability-adjusted life years (DALYs; i.e. years of healthy life lost) were caused by lead exposure in 2004. Although lead exposure in the general population of many countries has decreased since 2004 because of the continued phase-out of lead in gasoline, several recent epidemiological studies support the notion that low-exposure effects of lead occur in addition to those considered by the WHO (2009). It is therefore quite possible that the present global burden of disease caused by lead exposure is the same or greater than the one estimated in 2004.

    In addition to the estimates of lead-related disease and mortality, there are other well documented effects that were not included in the WHO estimates of the global burden of disease. This organization further summarized data indicating 9100 deaths and 125,000 DALYs per year in Bangladesh from arsenic in drinking water and that mercury exposure (mainly methylmercury) through fish consumption causes cognitive deficits and mild retardation in a considerable number of children. An increased incidence of myocardial infarction has been reported in populations with a high intake of methylmercury from fish and a low intake of polyunsaturated fatty acids. The public health impact of this observation of interaction between a nutritional factor and a toxic metal compound may be considerable. There is evidence for a role for relatively low occupational exposure to manganese as well as exposure in the general environment as a contributory factor to the increasing prevalence of Parkinson disease and there is a potentially great importance of metal exposure in early life as a risk factor for neurodegenerative disorders later in life. Recent epidemiological evidence indicates a role for cadmium in the general environment in increasing the occurrence of renal effects and osteoporosis, as well as cardiovascular diseases. There is no doubt thus that exposure to toxic metals and their compounds represents important causal factors contributing to the global burden of disease. Deficient dietary intake of essential metals in food in a global perspective was estimated by the WHO (2009) to cause 433,000 deaths and 15,580,000 DALYs from zinc deficiency and 273,000 deaths and 19,734,000 DALYs per year from iron deficiency.

    In view of the considerable global burden of disease caused by metals there is an obvious need for preventive action.

  • 35.
    Nordberg, G
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Skerfving, S
    Health effects of low dose exposure to toxic metals:: introduction and research recommendations2008Inngår i: Cell Biology and Toxicology, ISSN 0742-2091, E-ISSN 1573-6822, Vol. 24, s. 438-40Artikkel i tidsskrift (Fagfellevurdert)
  • 36.
    Nordberg, Gunnar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bernard, Alfred
    Diamond, Gary L.
    Duffus, John H.
    Illing, Paul
    Nordberg, Monica
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jin, Taiyi
    Skerfving, Staffan
    Risk assessment of effects of cadmium on human health (IUPAC Technical Report)2018Inngår i: Pure and Applied Chemistry, ISSN 0033-4545, E-ISSN 1365-3075, Vol. 90, nr 4, s. 755-808Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chemistry and Human Health, Division VII of the International Union on Pure and Applied Chemistry (IUPAC), provides guidance on risk assessment methodology and, as appropriate, assessment of risks to human health from chemicals of exceptional toxicity. The aim of this document is to describe dose-response relationships for the health effects of low-level exposure to cadmium, in particular, with an emphasis on causation. The term "cadmium" in this document includes all chemical species of cadmium, as well as those in cadmium compounds. Diet is the main source of cadmium exposure in the general population. Smokers and workers in cadmium industries have additional exposure. Adverse effects have been shown in populations with high industrial or environmental exposures. Epidemiological studies in general populations have also reported statistically significant associations with a number of adverse health effects at low exposures. Cadmium is recognized as a human carcinogen, a classification mainly based on occupational studies of lung cancer. Other cancers have been reported, but dose-response relationships cannot be defined. Cardiovascular disease has been associated with cadmium exposure in recent epidemiological studies, but more evidence is needed in order to establish causality. Adequate evidence of dose-response relationships is available for kidney effects. There is a relationship between cadmium exposure and kidney effects in terms of low molecular mass (LMM) proteinuria. Long-term cadmium exposures with urine cadmium of 2 nmol mmol(-1) creatinine cause such effects in a susceptible part of the population. Higher exposures result in increases in the size of these effects. This assessment is supported by toxicokinetic and toxicodynamic (TKTD) modelling. Associations between urine cadmium lower than 2 nmol mmol-1 creatinine and LMM proteinuria are influenced by confounding by co-excretion of cadmium with protein. A number of epidemiological studies, including some on low exposures, have reported statistically significant associations between cadmium exposure and bone demineralization and fracture risk. Exposures leading to urine cadmium of 5 nmol mmol-1 creatinine and more increase the risk of bone effects. Similar associations at much lower urine cadmium levels have been reported. However, complexities in the cause and effect relationship mean that a no-effect level cannot be defined. LMM proteinuria was selected as the critical effect for cadmium, thus identifying the kidney cortex as the critical organ, although bone effects may occur at exposure levels similar to those giving rise to kidney effects. To avoid these effects, population exposures should not exceed that resulting in cadmium values in urine of more than 2 nmol mmol(-1) creatinine. As cadmium is carcinogenic, a 'safe' exposure level cannot be defined. We therefore recommend that cadmium exposures be kept as low as possible. Because the safety margin for toxic effects in kidney and bone is small, or non-existent, in many populations around the world, there is a need to reduce cadmium pollution globally.

  • 37.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Biomarkers of exposure, effects and susceptibility in humans and their application in studies of interactions among metals in China2010Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 192, nr 1, s. 45-49Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Biomonitoring employs three categories of biomarkers: Biomarkers of exposure, i.e. measurements of metal concentrations in a compartment in the body reflecting external or internal exposure; Biomarkers of effects include early as well as clinical effects. Biomarkers of susceptibility indicate individuals with increased sensitivity of target molecules or metabolism causing increased target dose. The three categories of biomarkers were used in studies of health effects of metal exposures in China. Adverse effects on the kidney tubules with increased levels of the effect biomarkers beta-2-microglobulin in urine (UB2M) and urinary N-acetyl-beta-d-glucosaminidase (UNAG) were found among Cd exposed population groups in China. Among persons exposed to Cd, occupationally or in the general environment, the level of Cd-induced metallothionein mRNA (MTmRNA) in peripheral lymphocytes appeared as a useful indicator of the ability of individuals to synthesize MT. Persons with low MTmRNA levels displayed higher biomarker values of renal tubular damage than persons with high levels of MTmRNA, at comparable levels of urinary Cd. Other studies demonstrated the importance of auto-antibodies against metallothionein in plasma (MTab) in modifying the response to Cd. Persons with high levels of MTab displayed tubular proteinuria at lower levels of urinary Cd than persons with low levels of MTab. Studies in two metal contaminated areas in China demonstrated clear interactions between Cd and inorganic arsenic. Combined exposure, with increased levels of As and Cd in urine, caused considerably higher biomarker values of renal tubular damage, measured as increased urinary levels of B2M or NAG, than each of the exposures alone.

  • 38.
    Nordberg, Gunnar F
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Historical perspectives on cadmium toxicology.2009Inngår i: Toxicology and applied pharmacology, ISSN 1096-0333, Vol. 238, nr 3, s. 192-200Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.

  • 39.
    Nordberg, Gunnar F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lung cancer and exposure to environmental cadmium.2006Inngår i: Lancet Oncol, ISSN 1470-2045, Vol. 7, nr 2, s. 99-101Artikkel i tidsskrift (Fagfellevurdert)
  • 40.
    Nordberg, Gunnar F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fowler, Bruce A
    Risk assessment2015Inngår i: Handbook on the toxicology of metals: Volume I: General considerations / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg, Academic Press, 2015, 4, s. 461-486Kapittel i bok, del av antologi (Fagfellevurdert)
    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. Lead, cadmium, 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. Because of the increasing use of nanomaterials, a recent concern is the dose metric for inhaled metallic nanoparticles. Regardless of exposure route, the following risk assessment considerations are important: biomonitoring approaches, identification of the mode of action for toxicity of metallic species for hazard identification, determining dose-effect relationships, the construction of dose-response curves, and the development of benchmark doses for various metallic species, which 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 the formation of reactive oxygen species, modification of apoptosis, and methylation of DNA. 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.

  • 41.
    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, s. 281-301Kapittel 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.

  • 42.
    Nordberg, Gunnar F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Fowler, Bruce A.
    Risk assessment for human metal exposures: mode of action and kinetic approaches2018Bok (Annet vitenskapelig)
    Abstract [en]

    Risk Assessment for Human Metal Exposures: Mode of Action and Kinetic Approaches examines the current principles of risk assessment in human metal exposures, with a focus on Mode of Action(MOA), Toxicokinetic and Toxicodynamic (TKTD) considerations, and computer models. Derived from the highly respected Handbook on the Toxicology of Metals, Fourth Edition (2014), the book summarizes principles and methods and provides examples of how MOA -TKTD can be used. In addition, it presents tactics on how information generated by such methods can be confirmed by epidemiological data. Furthermore, it demonstrates how epidemiological data can be confirmed and evaluated by the examined models and considerations. This resource uniquely integrates several important topics, such as risk assessment, characterization, management and communication--the classic risk assessment paradigm--with mode of action, TKTD, and epidemiology, all topics related to human exposure. Written by pioneers in the field, this book is an essential reference for researchers, students and technicians in toxicology and risk assessment. Covers fundamental risk assessment concerns for the effects of metals on human health Provides an easy-to-use structure to quickly locate specific methods Uses case studies to illustrate the methods and theories described Written to be understood by students, researchers and industry workers who need to conduct risk assessment in metals and human health

  • 43.
    Nordberg, Gunnar F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fowler, Bruce ANordberg, Monica
    Handbook on the toxicology of metals2015Collection/Antologi (Fagfellevurdert)
  • 44.
    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, s. V-VKapittel i bok, del av antologi (Annet vitenskapelig)
  • 45.
    Nordberg, Gunnar F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fowler, Bruce A
    Nordberg, Monica
    Toxicology of metals: overview, definitions, concepts, and trends2015Inngår i: Handbook on the toxicology of metals: Volume I: General considerations / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg, Academic Press, 2015, 4, s. 3-14Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Metals and their compounds have long been recognized as important toxic agents, causing acute and chronic poisoning cases in occupational settings and in environmental high-exposure situations. In recent years it has been demonstrated in epidemiological studies that exposures in the general environment to low levels of toxic metals may make an important contribution to the global burden of disease. Furthermore, deficient intakes of essential metals through food give rise to a considerable burden of disease from a global perspective. There is an obvious need for preventive action to decrease this global burden of disease. It is also important to address current concerns for possible increases of metal exposures. This chapter highlights such concerns in relation to the current status of the scientific understanding of the metals included and discussed fully in the relevant chapters of this Handbook. Furthermore, it draws attention to future directions for 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.

  • 46.
    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.

  • 47.
    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, s. 1-9Kapittel 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.

  • 48.
    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, s. 117-145Kapittel 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.

  • 49.
    Nordberg, Gunnar F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Gerhardsson, Lars
    Mumtaz, Moiz M
    Ruiz, Patricia
    Fowler, Bruce A
    Interactions and Mixtures in Metal Toxicology2015Inngår i: Handbook on the Toxicology of Metals: Volume I: General considerations / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg, Academic Press, 2015, 4, s. 213-238Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]