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Cobalt in the hard metal production industry: exposure via inhalation and skin and the inflammatory response in human keratinocytes
Örebro University, School of Medical Sciences.
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cobalt is a strong sensitizer and can cause contact allergy upon both direct contact or from airborne exposure on the skin. In the skin, keratinocytes are the first cells to come in contact with the metal and will react and respond to the danger by triggering an alarm system resulting in an inflammatory response in the skin. Keratinocytes have been shown to produce IL-1β, which is one of the most potent  inflammatory agents in our body and is associated with a variety of diseases.

The aims of this thesis was to investigate cobalt air concentrations for different particle fractions for possible use as proxies for other article measures and to examine if cobalt skin and inhalable air exposure contributes to uptake. Also, to investigate the effect of cobalt on cultured human keratinocyte cell viability, pro-inflammatory cytokine/chemokine release and NLRP3 inflammasome activation using cells cultured at low or high calcium (the latter yielding a more differentiated cell type).

Air exposure to cobalt was found in all departments and for all work tasks in the hard metal production facility and exposures were in general below the Swedish OEL for inhalable cobalt. The highest exposure levels were found in the powder production department and for laboratory and furnace work. Good correlations for the mass based measures enable us to use the findings for future references. When personal inhalable air levels of cobalt, cobalt skin levels skin and biological monitoring of cobalt in blood were analysed, the skin exposure was determined to be import as a route of uptake. Skin exposure to cobalt in the hard metal industry, could further affect the total uptake in the same order of magnitude as air exposure. In vitro investigations of cobalt using the human keratinocyte cell line HaCaT, showed that CoCl2 triggered an alarm system in cells where the proinflammatory cytokines/chemokines IL-6, CXCL8 and CCL2, known to be involved in skin inflammation, were secreted in a time- and dosedependent manner. Comparing HaCaT cells of high- and low differentiation stages indicated that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis. CoCl2 exposure also resulted in secretion of the proinflammatory cytokines IL-1β and IL-18, and caspase-1, which indicates activation of the NLRP3 inflammasome in the cells. CoCl2 regulates the inflammasome both as primer and as an activator. Our mRNA results indicates a negative feedback mechanism in the inflamamsome due to the exposure. The inflammatory response in general is more dose than time dependent, which be important for understanding the mechanisms of allergic sensitization.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2020. , p. 91
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 220
Keywords [en]
Cobalt, cobalt chloride, skin, HaCaT, in vitro, cell viability, pro-inflammatory cytokines, NLRP3 inflammasome
National Category
Other Basic Medicine
Identifiers
URN: urn:nbn:se:oru:diva-81944ISBN: 978-91-7529-352-3 (print)OAI: oai:DiVA.org:oru-81944DiVA, id: diva2:1431208
Public defence
2020-10-09, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2020-05-19 Created: 2020-05-19 Last updated: 2020-09-28Bibliographically approved
List of papers
1. Occupational Exposure to Cobalt and Tungsten in the Swedish Hard Metal Industry: Air Concentrations of Particle Mass, Number, and Surface Area
Open this publication in new window or tab >>Occupational Exposure to Cobalt and Tungsten in the Swedish Hard Metal Industry: Air Concentrations of Particle Mass, Number, and Surface Area
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2016 (English)In: Annals of Occupational Hygiene, ISSN 0003-4878, E-ISSN 1475-3162, Vol. 60, no 6, p. 684-699Article in journal (Refereed) Published
Abstract [en]

Exposure to cobalt in the hard metal industry entails severe adverse health effects, including lung cancer and hard metal fibrosis. The main aim of this study was to determine exposure air concentration levels of cobalt and tungsten for risk assessment and dose-response analysis in our medical investigations in a Swedish hard metal plant. We also present mass-based, particle surface area, and particle number air concentrations from stationary sampling and investigate the possibility of using these data as proxies for exposure measures in our study. Personal exposure full-shift measurements were performed for inhalable and total dust, cobalt, and tungsten, including personal real-time continuous monitoring of dust. Stationary measurements of inhalable and total dust, PM2.5, and PM10 was also performed and cobalt and tungsten levels were determined, as were air concentration of particle number and particle surface area of fine particles. The personal exposure levels of inhalable dust were consistently low (AM 0.15mg m(-3), range <0.023-3.0mg m(-3)) and below the present Swedish occupational exposure limit (OEL) of 10mg m(-3) The cobalt levels were low as well (AM 0.0030mg m(-3), range 0.000028-0.056mg m(-3)) and only 6% of the samples exceeded the Swedish OEL of 0.02mg m(-3) For continuous personal monitoring of dust exposure, the peaks ranged from 0.001 to 83mg m(-3) by work task. Stationary measurements showed lower average levels both for inhalable and total dust and cobalt. The particle number concentration of fine particles (AM 3000 p·cm(-3)) showed the highest levels at the departments of powder production, pressing and storage, and for the particle surface area concentrations (AM 7.6 µm(2)·cm(-3)) similar results were found. Correlating cobalt mass-based exposure measurements to cobalt stationary mass-based, particle area, and particle number concentrations by rank and department showed significant correlations for all measures except for particle number. Linear regression analysis of the same data showed statistically significant regression coefficients only for the mass-based aerosol measures. Similar results were seen for rank correlation in the stationary rig, and linear regression analysis implied significant correlation for mass-based and particle surface area measures. The mass-based air concentration levels of cobalt and tungsten in the hard metal plant in our study were low compared to Swedish OELs. Particle number and particle surface area concentrations were in the same order of magnitude as for other industrial settings. Regression analysis implied the use of stationary determined mass-based and particle surface area aerosol concentration as proxies for various exposure measures in our study.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2016
Keywords
Cobalt exposure in the hard metal industry, occupational exposure, particle mass, particle number, particle surface area, personal exposure measurements, stationary measurements
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:oru:diva-50312 (URN)10.1093/annhyg/mew023 (DOI)000381195200003 ()27143598 (PubMedID)2-s2.0-84978734681 (Scopus ID)
Note

Funding Agency:

Swedish hard metal company

Available from: 2016-05-27 Created: 2016-05-16 Last updated: 2020-09-11Bibliographically approved
2. Biological monitoring of dermal and air exposure to cobalt at a Swedish hard metal production plant: does dermal exposure contribute to uptake?
Open this publication in new window or tab >>Biological monitoring of dermal and air exposure to cobalt at a Swedish hard metal production plant: does dermal exposure contribute to uptake?
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2017 (English)In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 77, no 4, p. 201-207Article in journal (Refereed) Published
Abstract [en]

Background: Occupational exposure to cobalt is well established in hard metal manufacture. Cobalt is known to cause contact allergy, asthma, hard metal lung disease, and lung cancer. The relationship between skin exposure and uptake determined in blood has not been extensively investigated.

Objective: To examine whether skin and inhalable air exposure to cobalt contributes to uptake, determined as cobalt in blood, in a hard metal manufacturing factory.

Methods: The amount of cobalt on the skin found with an acid wash technique, the air concentrations of inhalable cobalt and cobalt blood concentrations were determined and correlated in exposed workers.

Results: We found a significant rank correlation for cobalt concentrations on the skin, in inhalable air, and in blood (0.376-0.498). Multiple linear regression showed significant regression coefficients for cobalt skin exposure and blood (B = 0.01, p < 0.05) and for inhalable cobalt in air and blood (B = 49.1, p < 0.001). According to our model based on data from the regression analyses, a twofold increase in skin exposure levels at different air concentrations caused a 3 - 14% increase in blood levels.

Conclusions: Our data suggest that skin exposure to cobalt in the hard metal industry could affect the total uptake at the same order of magnitude as air exposure.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
Acid wash technique, blood concentration, cobalt, hard metal, skin absorption, skin exposure
National Category
Dermatology and Venereal Diseases Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:oru:diva-61031 (URN)10.1111/cod.12790 (DOI)000409110100002 ()28675438 (PubMedID)2-s2.0-85021784690 (Scopus ID)
Note

Funding Agency:

Swedish hard metal company

Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2020-09-11Bibliographically approved
3. Dose- and time-dependent changes in viability and IL-6, CXCL8 and CCL2 production by HaCaT-cells exposed to cobalt: Effects of high and low calcium growth conditions
Open this publication in new window or tab >>Dose- and time-dependent changes in viability and IL-6, CXCL8 and CCL2 production by HaCaT-cells exposed to cobalt: Effects of high and low calcium growth conditions
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(English)Manuscript (preprint) (Other academic)
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-85681 (URN)
Available from: 2020-09-11 Created: 2020-09-11 Last updated: 2020-09-11Bibliographically approved
4. Dermal exposure to cobalt: possible effects of cobalt exposure on inflammasome, cytokine and mRNA response studied in vitro in keratinocytes
Open this publication in new window or tab >>Dermal exposure to cobalt: possible effects of cobalt exposure on inflammasome, cytokine and mRNA response studied in vitro in keratinocytes
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(English)Manuscript (preprint) (Other academic)
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-85683 (URN)
Available from: 2020-09-11 Created: 2020-09-11 Last updated: 2020-09-11Bibliographically approved

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