Forskargrupp Gunnar Johanson

Hazardous chemical vapors in sea containers

Modern sea container transport has grown tremendously since its introduction in the 70s and numerous containers arrive with high levels of hazardous volatile chemicals, including carcinogens, in the interior air. This presents a serious health risk during inspection and unstuffing. The problem remains largely unaddressed due to ignorance, lack of suitable field instruments for chemical identification, and lack of suitable ventilation methods. The project addresses three topics:

• which chemicals are found in the air of containers arriving in Sweden and at what levels,
• personal exposure of workers unstuffing containers, and
• a new, easy to use and efficient method ventilation of containers prior to unstuffing.

Funding: AFA Försäkring and Forte

Publications

• Johanson G, Svedberg U. A novel method for pre-ventilation of shipping containers. Int J  Hyg Environ Health 220 (2020) https://doi.org/10.1016/j.ijheh.2020.113626
• Svedberg U, Johanson G. Occurrence of fumigants and hazardous off-gassing chemicals in shipping containers arriving in Sweden. Ann Work Expo Health 61 (2016) 195-206.
• Svedberg U, Johanson G. Work inside ocean freight containers – Personal exposure to fumigants and off-gassing chemicals. Ann Occup Hyg 57 (2013) 1128-1137.
• Svedberg U, Johanson G. Förekomst av gasformiga bekämpningsmedel och kemikalier i containrar: pilotstudie vid importkontrollen i Göteborgs hamn. IMM-Rapport 1 (2011).

Conference presentations

• Johanson G, Svedberg U. VOCs in containers arriving in Sweden - Occurrence, personal exposure, and sampling and ventilation strategies IOHA 10th International Scientific Conference, London 2015.
• Johanson G, Svedberg U. Occurrence and levels of VOCs in containers arriving in Sweden, including aspects on personal exposure, ventilation and sampling position. 7th International Workshop "How to handle imported containers safely, Berlin, 2014.
• Svedberg U, Johanson G. Work inside ocean freight containers- a largely unrecognized work hazard. AIHA Fall Conference, Washington DC, 2014.
• Johanson G. Work inside ocean freight containers. MareHeal, Gothenburg, 2013.
• Johanson G, Svedberg U. Occurrence of gaseous pesticides and other hazardous volatiles in sea containers arriving in Sweden. Society of Toxicology Annual Meeting, San Antonio, 2013.
• Svedberg U, Johanson G. Fumigants and VOCs in ocean freight containers - identification, exposure & prevention. International Symposium on Maritime Health, Brest, 2013.
• Svedberg U, Johanson G. Control of toxic gases in ocean freight containers. 11th International Symposium on Protection against Chemical and Biological Warfare Agents, Stockholm, 2013.

Seminars

• Bekämpningsmedel och kemikalier i containrar – hur stora är riskerna? KI Solna, 18 februari 2011.
• Farliga kemiska ämnen i containrar – förekomst, nivåer, utvädring och yrkesmässig exponering. KI Solna, 15 maj 2014.
• Hantering av kemiska risker vid urlastning av sjöfartscontainrar. KI Solna, 23 oktober 2019.

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The Nordic Expert Group

The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals (NEG) is a Nordic collaboration for production of criteria documents on chemicals for occupational exposure limits. The main task of NEG is to produce criteria documents to be used by the regulatory authorities of the Nordic countries as the scientific basis for setting occupational exposure limits (OELs) for chemical substances. NEG consists of scientific experts from the Nordic countries representing different fields of science, such as toxicology, occupational hygiene and occupational medicine. The documents, written in English, are published by the University of Gothenburg in the scientific serial Arbete och Hälsa. The documents are also available as pdf downloads via this website under Publications.

Funding: NEG is mainly financed by the Swedish Work Environment Authority and the Norwegian Ministry of Labour and Social Affairs. All countries contribute with scientific expertise..

Home page: www.nordicexpertgroup.org

Recent publications

• Sjögren B, Bigert C, Gustavsson P. The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals. 153. Occupational chemical exposures and cardiovascular disease. Arbete och Hälsa 54:2 (2020) 428 pages.
• Wastensson G, Eriksson K. The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals. 152. Inorganic chloramines. Arbete och Hälsa 53:2 (2019) 110 pages.

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Toxicokinetic modelling

Toxicokinetic (TK) modeling is an important tool in several areas of toxicology. A major reason is the target dose concept, i.e. that a quantitative relationship between the target dose and the toxic effect can be expected. Thus, by using TK models, factors that are known or expected to influence the relationship between external exposure or administered dose and target dose may be accounted for. Thereby, some of the uncertain factors associated with toxicological risk assessment may be reduced. Important factors include route of exposure, exposure pattern, exposure duration, physical exercise, body build, enzyme induction, enzyme inhibition, and species differences in size, physiology, and metabolism.

TK modeling may also be used the development of biological exposure monitoring and biological exposure limits. The TK model is then not used to calculate target doses but rather the relationship between external exposure and biomarker level in e.g. blood, urine, or exhaled air.

Thirdly, TK models may be used to strengthen experimental results by linking data obtained under different experimental conditions in a uniform model. Once the model is established, it may be expanded to facilitate extrapolation to other setting, for example  other exposure routes or species.

Physiologically based pharmacokinetic (PBPK) models are particularly useful in the above contexts. PBPK models are constructed from quantitative data on chemical-independent (e.g. organ volumes, blood flows, lung ventilation, body growth) as well as chemical-dependent (e.g. tissue partitioning, protein binding, metabolic pathways, metabolic rates) factors.

Select  publications

• Amzal B, Julin B, Vahter M, Wolk A, Johanson G, Åkesson A. Impact of population variability in cadmium toxicokinetics on estimates of exposure limits; a population-based approach. Environ Health Perspect 117 (2009) 1293-1301.
• Barton HA, Chiu WA, Setzer W, Andersen ME, Bailer AJ, Bois FY, DeWoskin RS, Hays S, Johanson G, Jones N, Loizou G, MacPhail RC, Portier CJ, Spendiff M, Tan YM. Characterizing uncertainty and variability in physiologically-based pharmacokinetic (PBPK) models: State of the science and needs for research and implementation. Tox Sci 99 (2007) 395-402.
• Carlander U, Li D, Jolliet O, Emond C, Johanson G. Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles. Int J Nanomedicine 11 (2016) 625-640.
• Carlander U, Moto TP, Desalegn AA, Yokel RA, Johanson G. Physiologically based pharmacokinetic modeling of nanoceria systemic distribution in rats suggests dose- and route-dependent biokinetics. Int J Nanomed 13 (2018) 2631-2646.
• Ernstgård L, Pexaras A, Johanson G. Washout kinetics of ethanol from the airways following inhalation of ethanol vapors and use of mouthwash. Clin Toxicol 58 (2020) 171-177.
• Ernstgård L, Sjögren B, Gunnare S, Johanson G. Blood and exhaled air can be used for biomonitoring of hydrofluorocarbon exposure Toxicol Lett 225 (2014) 102-109.
• Johanson G. Modeling of Disposition. In: Reference Module in Biomedical Sciences, 3rd ed. Elsevier (2018) pp 165-187. http://www.sciencedirect.com/science/article/pii/B9780128012383018894
• Laux P, Riebeling C, Booth AM, Brain JD, Brunner J, Cerillo C, Creutzenberg O, Estrela-Lopis I, Gebel T, Johanson G, Jungnickel H, Kock H, Tentschert J, Tlili A, Schäffer A, Sips AJAM, Yokel RA, Luch A. Biokinetics of nanomaterials: the role of biopersistence. NanoImpact 6 (2017) 69-80.
• Mörk AK, Johanson G. Chemical-specific adjustment factors for intraspecies variability of acetone toxicokinetics using a probabilistic approach. Toxicol Sci 116 (2010) 336-348.
• Mörk A-K, Jonsson F, Johanson G. Bayesian population analysis of a washin-washout physiologically based pharmacokinetic model for acetone. Toxicol Appl Pharmacol 240 (2009) 423-432.
• Stamyr K, Mörk AK, Johanson G. Physiologically based pharmacokinetic modeling of hydrogen cyanide levels in human breath. Arch Toxicol 89 (2015) 1287-1296.
• Verner MA, McDougall R, Johanson G. Using population physiologically based pharmacokinetic modeling to determine optimal sampling times and to interpret biological exposure markers: the example of occupational exposure to styrene. Toxicol Lett 213 (2012) 299-304.

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Genomics of lung function development to identify susceptibility factors for chronic lung diseases

Only 15-20% of smokers develop COPD thereby strongly indicating the genetic predisposition of this disease. Moreover, more than 40% of the causes of COPD is attributed to causes other than smoking. Failure to attain peak lung function (eg. total lung capacity) by early adulthood is considered as a risk for later onset of COPD. This is plausibly related to the fact that lung developmental events are recollected in genetic sub-routines during repair and remodeling processes. In this project we aim to study the genomics of lung function development using mouse models, and elucidate the mechanism through in vitro studies and associate the findings in human cohorts.

• Swedish Heart Lung Foundation
• VINNOVA, Sweden’s Innovation Agency
• IMM Strategic Grant

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Yrkesmässiga kemiska exponeringar och hjärtkärlsjukdom

Under de senaste decennierna har flera typer av studier påvisat ett samband mellan partikulära luftföroreningar i stadsmiljöer och ökad förekomst av hjärtsjukdom. Enligt en teori skapar inandning av partiklar en låggradig inflammation som i det korta perspektivet påverkar blodets koagulation och det långa perspektivet ökar risken för ateroskleros. Inom detta område studerar vi dels yrkesmässig exponering för luftföroreningar och förekomst av hjärtsjukdom och dels exponering för luftföroreningar (i kammarförsök och fältstudier) och påverkan på inflammatoriska markörer. De inflammatoriska markörerna är bland andra fibrinogen och C-reaktivt protein (CRP) som är kända riskfaktorer för hjärtsjukdom.

I en översikt har vi presenterat kunskapsläget med avseende på flera yrkesmässiga exponeringar och sambandet med hjärtkärlsjukdom: Sjögren B, Bigert C och Gustavsson P. The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals. 153. Occupational chemical exposures and cardiovascular disease. Arbete och Hälsa 2020; 54: 2, 428 sidor (www.nordicexpertgroup.org).

Publikationer

Gustavsson P, Sjögren B, Broberg K, Albin M. Common occupational chemical exposures. In Environmental exposures and cardiovascular disease, editor Leander K. IMM-rapport 2019; 1: 106–142.

SBU. Arbetsmiljöns betydelse för hjärt-kärlsjukdom - Exponering för kemiska ämnen. Sakkunniga: Theorell T, Albin M, Hogstedt C, Sjögren B. SBU Rapport 261/2017, 218 sidor.

Ernstgård L, Bottai M, Johanson G, Sjögren B. Down-regulation of the inflammatory response after short-term exposure to low levels of chemical vapours. Occup Environ Med 2019; 76: 482-487.

Westberg H, Hedbrant A, Persson A, Bryngelsson IL, Johansson A, Ericsson A, Sjögren B, Stockfelt L, Särndahl E, Andersson L. Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in Swedish iron foundries, in particular respirable quartz. Int Arch Occup Environ Health 2019; 92: 1087-1098.

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Linking accumulation and distribution to the toxicity of perfluorinated alkyl acids in zebrafish embryo

Long-chain perfluorinated alkyl acids (PFAA) are currently substituted by short-chain variants based on the view that these are less toxic. Our studies suggest that the difference in toxic potency between short-chain and long-chain PFAA is due to differences in accumulation and distribution in the body.

Perfluorinated alkyl acid carboxylates and sulfonates (PFAA) are a group of persistent organofluorine chemicals that have been broadly used in commercial and industrial products (e.g., surfactants, fluorinated polymers, coatings, fire-resistant foams). Several studies show that PFAA may cause multiple adverse health effects. Many different PFAA have been detected in serum samples in humans worldwide and relative levels in autopsy tissues indicate that the distribution of these chemicals in humans varies depending on their chemical properties such as chain lengths and functional groups. Short-chain PFAA are believed to be less toxic compared to long-chain PFAA which has led to replacement of the long-chain PFAA to ones with shorter chain. Still, it is poorly understood how the toxicity links to toxicokinetics (absorption, biotransformation, distribution and excretion) chemical properties.

The aim of the project is to describe and compare the toxicokinetic profiles for four PFAA (PFOS, PFHxS, PFOA, PFBA) with different chain lengths and functional groups in zebrafish embryo. To this end, we will address the following objectives:

1. Quantification of internal PFAA accumulation in zebrafish embryo to explain toxicity differences of phenotypical malformations (see Vogs et al. 2019, in collaboration with Johan Lindberg, RISE Research Institutes of Sweden)
2. Applying Mass spectrometry imaging and autoradiography to visualize PFAAs distribution in zebrafish embryo (in collaboration with Per Andrén, Pharmaceutical Biosciences, Uppsala University; Maria Jönsson, Department of Organismal Biology, Environmental Toxicology),
3. Linking PFAA accumulation and distribution differences to effect biomarkers (i.e. transcriptomics) (in collaboration with Joëlle Rüegg, Department of Organismal Biology, Environmental Toxicology)

Funding

Formas, seeding grant from Centre for Reproductive Biology

Publication

Carolina Vogs, Gunnar Johanson, Markus Näslund, Sascha Wulff, Marcus Sjödin, Magnus Hellstrandh, Johan Lindberg, and Emma Wincent.  Toxicokinetics of Perfluorinated Alkyl Acids Influences Their Toxic Potency in the Zebrafish Embryo (Danio rerio). Environ. Sci. Technol., 2019, 53 (7), pp 3898–3907. https://pubs.acs.org/doi/10.1021/acs.est.8b07188

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