Gunnar Johanson | Karolinska Institutet (original) (raw)

Papers by Gunnar Johanson

Research paper thumbnail of A scoping review of evaluations of and recommendations for default uncertainty factors in human health risk assessment

Journal of Applied Toxicology

Uncertainty factors (UFs) are used to account for uncertainties and variability when setting expo... more Uncertainty factors (UFs) are used to account for uncertainties and variability when setting exposure limits or guidance values. Starting from a proposal of a single UF of 100 to extrapolate from an animal NOAEL to a human acceptable exposure, the aspects of uncertainty and number of UFs have diversified and today there are several risk assessment guidelines that contain schemes of default UFs of varying complexity. In the present work, we scoped the scientific literature on default UFs to map developments regarding recommendations and evaluations of these. We identified 91 publications making recommendations for one or several UFs and 55 publications evaluating UFs without making explicit recommendations about numerical values; these were published between 1954 and 2021. The 2000s was the decade with the largest number of publications, interspecies differences and intraspecies variability being the most frequent topics. The academic sector has been the most active (76 out of 146 pu...

Research paper thumbnail of REACH DNELs and national OELs: Conflicting or complementary limit setting?

Research paper thumbnail of Heated Tobacco Products: Insights into Composition and Toxicity

Toxics

Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating ... more Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating (350 °C) reconstituted tobacco rather than combustion (900 °C) as in conventional cigarettes. HTP sticks containing reconstituted tobacco come in various flavours such as menthol, citrus, etc., like electronic cigarette liquids. Thus, the composition of HTP aerosol will also vary according to the flavouring agents added. Overall, the content of toxic chemicals in HTP aerosol appears to be lower than in cigarette smoke. However, the concentrations of more than twenty harmful and potentially harmful constituents have been reported to be higher in HTP aerosol than in cigarette smoke. Further, several toxic compounds not detected in cigarette smoke are also reported in HTP aerosol. Thus, the risks of HTP use remain unknown. Most of the available data on the composition and health effects of mainstream HTP aerosol exposure are generated by the tobacco industry. Few independent studies have re...

Research paper thumbnail of Relations between concentrations of perfluoroalkyl substances (PFAS) in drinking water and serum in adults living near PFAS hotspots

ISEE Conference Abstracts

Research paper thumbnail of NANoREG framework for the safety assessment of nanomaterials

Stefania Gottardo, Maria Alessandrelli, Valeria Amenta, Rambabu Atluri, Grazia Barberio, Cindy Be... more Stefania Gottardo, Maria Alessandrelli, Valeria Amenta, Rambabu Atluri, Grazia Barberio, Cindy Bekker, Philippe Bergonzo, Eric Bleeker, Andy M. Booth, Teresa Borges, Patrizia Buttol, David Carlander, Stefano Castelli, Sylvie Chevillard, Simon Clavaguera, Susan Dekkers, Camilla Delpivo, Paola Di Prospero Fanghella, Maria Dusinska, Juha Einola, Elina Ekokoski, Carlos Fito, Helena Gouveia, Romain Grall, Karl Hoehener, Paula Jantunen, Gunnar Johanson, Peter Laux, Hans Christian Lehmann, Riitta Leinonen, Agnieszka Mech, Christian Micheletti, Cornelle Noorlander, Mats Olof-Mattsson, Agnes Oomen, Laia Quiros Pesudo, Maria Letizia Polci, Adriele Prina-Mello, Kirsten Rasmussen, Hubert Rauscher, Araceli Sanchez Jimenez, Juan Riego Sintes, Simona Scalbi, Jacques-Aurélien Sergent, Helene Stockmann-Juvala, Myrtill Simko, Adriënne Sips, Blanca Suarez, Abdelqader Sumrein, Martie van Tongeren, Socorro Vázquez-Campos, Nádia Vital, Tobias Walser, Susan Wijnhoven, Hugues Crutzen

Research paper thumbnail of House painters' exposure to glycols and glycol ethers from water based paints

Research paper thumbnail of The ICOH Workshop 2008 on skin notation

Research paper thumbnail of Addressing the challenges of E-cigarette safety profiling by assessment of pulmonary toxicological response in bronchial and alveolar mucosa models

Scientific Reports, 2020

Limited toxicity data on electronic cigarette (ECIG) impede evidence-based policy recommendations... more Limited toxicity data on electronic cigarette (ECIG) impede evidence-based policy recommendations. We compared two popular mixed fruit flavored ECIG-liquids with and without nicotine aerosolized at 40 W (E-smoke) with respect to particle number concentrations, chemical composition, and response on physiologically relevant human bronchial and alveolar lung mucosa models cultured at air–liquid interface. E-smoke was characterized by significantly increased particle number concentrations with increased wattage (25, 40, and 55 W) and nicotine presence. The chemical composition of E-smoke differed across the two tested flavors in terms of cytotoxic compounds including p-benzoquinone, nicotyrine, and flavoring agents (for example vanillin, ethyl vanillin). Significant differences in the expression of markers for pro-inflammation, oxidative stress, tissue injury/repair, alarm anti-protease, anti-microbial defense, epithelial barrier function, and epigenetic modification were observed betwe...

Research paper thumbnail of Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin—A Human Experimental Study

Environmental Health Perspectives, 2021

Background: The filaggrin protein is important for skin barrier structure and function. Loss-of-f... more Background: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. Objective: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. Method: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects’ urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. Results: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20–22 repeats) and high FLG CNV (23–24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUC(0–40h)) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC(0–40h)) for pyrimethanil than wt carriers with low and high CNV, respectively. Conclusion: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310

Research paper thumbnail of Management of bias and conflict of interest among occupational exposure limit expert groups

Regulatory Toxicology and Pharmacology, 2021

Our aim was to evaluate policies and procedures for management of conflict of interest (CoI) and ... more Our aim was to evaluate policies and procedures for management of conflict of interest (CoI) and other sources of bias, implemented in Occupational Exposure Limit (OEL) expert groups. First, we compiled procedural criteria applicable to OEL-setting, based on literature on CoI and systematic reviews. Second, we identified 58 global OEL-sources and sought the underlying expert groups and operating procedures. We identified eleven active groups, of which five have documented CoI policies. In all five, CoI management is based on declarations of interests (DoIs) and removal of experts from decisions in which they have an interest. Notable differences include publication of DoIs (three of five groups), limitation of DoI to current interests (two groups), quantitative limits for financial interests (none specified to ≥€10,000 per interest), control procedures for undisclosed CoI (one group), and procedures in case of discovery of undisclosed CoI (three groups). Methods to evaluate study quality are described by three groups, while reproducible and comprehensive strategies to identify and select data receive less attention. We conclude that procedures to manage CoI and bias are not broadly implemented, or at least not openly and transparently communicated. This lack of visible procedures is remarkable, considering OEL's impact on health and economy.

Research paper thumbnail of Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

Alternatives to Laboratory Animals, 1993

This presentation addresses some aspects of the methodology, advantages and problems associated w... more This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target d...

Research paper thumbnail of Reflections on the OECD guidelines for in vitro skin absorption studies

Regulatory Toxicology and Pharmacology, 2020

Research paper thumbnail of Flavor, Nicotine Content, Vaping Regime, and Lung Region Matter: Alarm Anti-Proteases and Anti-Microbial Defensins Are Important for Electronic Cigarette Related Pulmonary Response

B18. E-CIGARETTE AND VAPING INDUCED RESPIRATORY HEALTH OUTCOMES - IT IS NOT THAT SIMPLE, 2020

Research paper thumbnail of Assessment of Biomass Smoke Induced Pulmonary Response and the Protective Effect of Magnolol Using Physiologically Relevant Normal- and Chronic Bronchitis-Like Bronchial Mucosa Models

B26. HEALTH EFFECTS CAUSED BY AIR POLLUTION - FROM RNAseq TO POPULATION OUTCOMES, 2020

Research paper thumbnail of The 2008 ICOH Workshop on Skin Notation

La Medicina del lavoro

On 29 March 2008 the International Commission on Occupational Health (ICOH) Scientific Committee ... more On 29 March 2008 the International Commission on Occupational Health (ICOH) Scientific Committee on Occupational and Environmental Dermatoses organized a Skin Notation Workshop hosted by the 11th International Percutaneous Penetration Perspectives Conference (La Grande Motte, France). Skin notation (S) was chosen as a topic for discussion because this is the only example of existing regulation in the field of dermal risk assessment. The issue was discussed in a previous workshop held in Siena, Italy in 2006 with the objective of focussing on the problems related to S, the different assignment criteria and the attempts to improve the S system made by various international and governmental agencies. A position paper was subsequently published. The workshop in France was a continuation of this activity with the aim of evaluating how the different strategies can improve S. The Workshop was divided into two sessions. The first was dedicated to lectures focused on different aspects of S. ...

Research paper thumbnail of Occurrence of Fumigants and Hazardous Off-gassing Chemicals in Shipping Containers Arriving in Sweden

Annals of Work Exposures and Health, 2017

Research paper thumbnail of Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients: identification of gaps in knowledge and data

Critical Reviews in Toxicology, 2019

Research paper thumbnail of Silica, silicosis and lung cancer: what level of exposure is acceptable?

La Medicina del Lavoro, 2018

Silica, silicosis and lung cancer: what level of exposure is acceptable?

Research paper thumbnail of Quantitative Relationships of Perfluoroalkyl Acids in Drinking Water Associated with Serum Concentrations Above Background in Adults Living Near Contamination Hotspots in Sweden

Research paper thumbnail of The Global Landscape of Occupational Exposure Limits—Implementation of Harmonization Principles to Guide Limit Selection

Journal of Occupational and Environmental Hygiene, 2015

Research paper thumbnail of A scoping review of evaluations of and recommendations for default uncertainty factors in human health risk assessment

Journal of Applied Toxicology

Uncertainty factors (UFs) are used to account for uncertainties and variability when setting expo... more Uncertainty factors (UFs) are used to account for uncertainties and variability when setting exposure limits or guidance values. Starting from a proposal of a single UF of 100 to extrapolate from an animal NOAEL to a human acceptable exposure, the aspects of uncertainty and number of UFs have diversified and today there are several risk assessment guidelines that contain schemes of default UFs of varying complexity. In the present work, we scoped the scientific literature on default UFs to map developments regarding recommendations and evaluations of these. We identified 91 publications making recommendations for one or several UFs and 55 publications evaluating UFs without making explicit recommendations about numerical values; these were published between 1954 and 2021. The 2000s was the decade with the largest number of publications, interspecies differences and intraspecies variability being the most frequent topics. The academic sector has been the most active (76 out of 146 pu...

Research paper thumbnail of REACH DNELs and national OELs: Conflicting or complementary limit setting?

Research paper thumbnail of Heated Tobacco Products: Insights into Composition and Toxicity

Toxics

Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating ... more Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating (350 °C) reconstituted tobacco rather than combustion (900 °C) as in conventional cigarettes. HTP sticks containing reconstituted tobacco come in various flavours such as menthol, citrus, etc., like electronic cigarette liquids. Thus, the composition of HTP aerosol will also vary according to the flavouring agents added. Overall, the content of toxic chemicals in HTP aerosol appears to be lower than in cigarette smoke. However, the concentrations of more than twenty harmful and potentially harmful constituents have been reported to be higher in HTP aerosol than in cigarette smoke. Further, several toxic compounds not detected in cigarette smoke are also reported in HTP aerosol. Thus, the risks of HTP use remain unknown. Most of the available data on the composition and health effects of mainstream HTP aerosol exposure are generated by the tobacco industry. Few independent studies have re...

Research paper thumbnail of Relations between concentrations of perfluoroalkyl substances (PFAS) in drinking water and serum in adults living near PFAS hotspots

ISEE Conference Abstracts

Research paper thumbnail of NANoREG framework for the safety assessment of nanomaterials

Stefania Gottardo, Maria Alessandrelli, Valeria Amenta, Rambabu Atluri, Grazia Barberio, Cindy Be... more Stefania Gottardo, Maria Alessandrelli, Valeria Amenta, Rambabu Atluri, Grazia Barberio, Cindy Bekker, Philippe Bergonzo, Eric Bleeker, Andy M. Booth, Teresa Borges, Patrizia Buttol, David Carlander, Stefano Castelli, Sylvie Chevillard, Simon Clavaguera, Susan Dekkers, Camilla Delpivo, Paola Di Prospero Fanghella, Maria Dusinska, Juha Einola, Elina Ekokoski, Carlos Fito, Helena Gouveia, Romain Grall, Karl Hoehener, Paula Jantunen, Gunnar Johanson, Peter Laux, Hans Christian Lehmann, Riitta Leinonen, Agnieszka Mech, Christian Micheletti, Cornelle Noorlander, Mats Olof-Mattsson, Agnes Oomen, Laia Quiros Pesudo, Maria Letizia Polci, Adriele Prina-Mello, Kirsten Rasmussen, Hubert Rauscher, Araceli Sanchez Jimenez, Juan Riego Sintes, Simona Scalbi, Jacques-Aurélien Sergent, Helene Stockmann-Juvala, Myrtill Simko, Adriënne Sips, Blanca Suarez, Abdelqader Sumrein, Martie van Tongeren, Socorro Vázquez-Campos, Nádia Vital, Tobias Walser, Susan Wijnhoven, Hugues Crutzen

Research paper thumbnail of House painters' exposure to glycols and glycol ethers from water based paints

Research paper thumbnail of The ICOH Workshop 2008 on skin notation

Research paper thumbnail of Addressing the challenges of E-cigarette safety profiling by assessment of pulmonary toxicological response in bronchial and alveolar mucosa models

Scientific Reports, 2020

Limited toxicity data on electronic cigarette (ECIG) impede evidence-based policy recommendations... more Limited toxicity data on electronic cigarette (ECIG) impede evidence-based policy recommendations. We compared two popular mixed fruit flavored ECIG-liquids with and without nicotine aerosolized at 40 W (E-smoke) with respect to particle number concentrations, chemical composition, and response on physiologically relevant human bronchial and alveolar lung mucosa models cultured at air–liquid interface. E-smoke was characterized by significantly increased particle number concentrations with increased wattage (25, 40, and 55 W) and nicotine presence. The chemical composition of E-smoke differed across the two tested flavors in terms of cytotoxic compounds including p-benzoquinone, nicotyrine, and flavoring agents (for example vanillin, ethyl vanillin). Significant differences in the expression of markers for pro-inflammation, oxidative stress, tissue injury/repair, alarm anti-protease, anti-microbial defense, epithelial barrier function, and epigenetic modification were observed betwe...

Research paper thumbnail of Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin—A Human Experimental Study

Environmental Health Perspectives, 2021

Background: The filaggrin protein is important for skin barrier structure and function. Loss-of-f... more Background: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. Objective: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. Method: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects’ urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. Results: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20–22 repeats) and high FLG CNV (23–24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUC(0–40h)) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC(0–40h)) for pyrimethanil than wt carriers with low and high CNV, respectively. Conclusion: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310

Research paper thumbnail of Management of bias and conflict of interest among occupational exposure limit expert groups

Regulatory Toxicology and Pharmacology, 2021

Our aim was to evaluate policies and procedures for management of conflict of interest (CoI) and ... more Our aim was to evaluate policies and procedures for management of conflict of interest (CoI) and other sources of bias, implemented in Occupational Exposure Limit (OEL) expert groups. First, we compiled procedural criteria applicable to OEL-setting, based on literature on CoI and systematic reviews. Second, we identified 58 global OEL-sources and sought the underlying expert groups and operating procedures. We identified eleven active groups, of which five have documented CoI policies. In all five, CoI management is based on declarations of interests (DoIs) and removal of experts from decisions in which they have an interest. Notable differences include publication of DoIs (three of five groups), limitation of DoI to current interests (two groups), quantitative limits for financial interests (none specified to ≥€10,000 per interest), control procedures for undisclosed CoI (one group), and procedures in case of discovery of undisclosed CoI (three groups). Methods to evaluate study quality are described by three groups, while reproducible and comprehensive strategies to identify and select data receive less attention. We conclude that procedures to manage CoI and bias are not broadly implemented, or at least not openly and transparently communicated. This lack of visible procedures is remarkable, considering OEL's impact on health and economy.

Research paper thumbnail of Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

Alternatives to Laboratory Animals, 1993

This presentation addresses some aspects of the methodology, advantages and problems associated w... more This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target d...

Research paper thumbnail of Reflections on the OECD guidelines for in vitro skin absorption studies

Regulatory Toxicology and Pharmacology, 2020

Research paper thumbnail of Flavor, Nicotine Content, Vaping Regime, and Lung Region Matter: Alarm Anti-Proteases and Anti-Microbial Defensins Are Important for Electronic Cigarette Related Pulmonary Response

B18. E-CIGARETTE AND VAPING INDUCED RESPIRATORY HEALTH OUTCOMES - IT IS NOT THAT SIMPLE, 2020

Research paper thumbnail of Assessment of Biomass Smoke Induced Pulmonary Response and the Protective Effect of Magnolol Using Physiologically Relevant Normal- and Chronic Bronchitis-Like Bronchial Mucosa Models

B26. HEALTH EFFECTS CAUSED BY AIR POLLUTION - FROM RNAseq TO POPULATION OUTCOMES, 2020

Research paper thumbnail of The 2008 ICOH Workshop on Skin Notation

La Medicina del lavoro

On 29 March 2008 the International Commission on Occupational Health (ICOH) Scientific Committee ... more On 29 March 2008 the International Commission on Occupational Health (ICOH) Scientific Committee on Occupational and Environmental Dermatoses organized a Skin Notation Workshop hosted by the 11th International Percutaneous Penetration Perspectives Conference (La Grande Motte, France). Skin notation (S) was chosen as a topic for discussion because this is the only example of existing regulation in the field of dermal risk assessment. The issue was discussed in a previous workshop held in Siena, Italy in 2006 with the objective of focussing on the problems related to S, the different assignment criteria and the attempts to improve the S system made by various international and governmental agencies. A position paper was subsequently published. The workshop in France was a continuation of this activity with the aim of evaluating how the different strategies can improve S. The Workshop was divided into two sessions. The first was dedicated to lectures focused on different aspects of S. ...

Research paper thumbnail of Occurrence of Fumigants and Hazardous Off-gassing Chemicals in Shipping Containers Arriving in Sweden

Annals of Work Exposures and Health, 2017

Research paper thumbnail of Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients: identification of gaps in knowledge and data

Critical Reviews in Toxicology, 2019

Research paper thumbnail of Silica, silicosis and lung cancer: what level of exposure is acceptable?

La Medicina del Lavoro, 2018

Silica, silicosis and lung cancer: what level of exposure is acceptable?

Research paper thumbnail of Quantitative Relationships of Perfluoroalkyl Acids in Drinking Water Associated with Serum Concentrations Above Background in Adults Living Near Contamination Hotspots in Sweden

Research paper thumbnail of The Global Landscape of Occupational Exposure Limits—Implementation of Harmonization Principles to Guide Limit Selection

Journal of Occupational and Environmental Hygiene, 2015