Elsevier

Toxicology

Volume 287, Issues 1–3, 5 September 2011, Pages 153-159
Toxicology

Relationship between pulmonary and systemic markers of exposure to multiple types of welding particulate matter

https://doi.org/10.1016/j.tox.2011.06.008Get rights and content

Abstract

Welding results in a unique and complex occupational exposure. Recent epidemiological studies have shown an increased risk of cardiovascular disease following welding fume exposure. In this study, we compared the induction of pulmonary and systemic inflammation following exposure to multiple types of welding fumes. Mice were exposed to 340 μg of manual metal arc stainless steel (MMA-SS), gas metal arc-SS (GMA-SS) or GMA-mild steel (GMA-MS) by pharyngeal aspiration. Mice were sacrificed at 4 and 24 h post-exposure to evaluate various parameters of pulmonary and systemic inflammation. Alterations in pulmonary gene expression by a custom designed TaqMan array showed minimal differences between the fumes at 4 h. Conversely at 24 h, gene expression changes were further increased by SS but not GMA-MS exposure.

These findings were associated with the surrogate marker of systemic inflammation, liver acute phase gene induction. Interestingly, stress response genes in cardiovascular tissues were only increased following MMA-SS exposure. These effects were related to the initial level of pulmonary cytotoxicity, as measured by lactate dehydrogenase activity, which was greatest following MMA-SS exposure. In conclusion, varying types of welding fumes elicit quantitatively different systemic inflammatory and/or stress responses.

Introduction

Epidemiological studies have shown increased cardiovascular mortality and morbidity following particulate matter exposure (Brook et al., 2010, Dockery et al., 1993, Pope et al., 1992, Samet et al., 2000, Schwartz and Morris, 1995). Subsequent human and animal studies support these findings: therefore, biological mechanisms have been proposed to explain the effects. First, the direct mechanism hypothesizes that particles, most likely ultrafine in size, and/or soluble metals or organic compounds enter the circulation and induce biological effects (Brook et al., 2010, Nemmar et al., 2001, Nemmar et al., 2002, Oberdorster et al., 2002). Second, an indirect mechanism is activation of the autonomic nervous system resulting in an imbalance between sympathetic and parasympathetic stimulation (Brook et al., 2010, Gold et al., 2000, Magari et al., 2001, Pope et al., 1999). Finally, another proposed indirect effect is that particle exposure results in a pulmonary inflammatory response and release of mediators into the general circulation (Brook et al., 2010, Seaton et al., 1995). These mechanisms may combine to produce effects including endothelial dysfunction, decreased heart rate variability, enhanced coagulation potential and increased progression of atherosclerosis (Brook et al., 2010). While the indirect hypothesis of spill-over of pulmonary inflammation has the strongest mechanistic support, to some degree, all three mechanisms may work in concert to produce systemic effects (Brook et al., 2010).

Welding results in a unique and complex occupational exposure. The aerosol generated from welding contains both gases and a fume which consists of metal oxide particulate matter (Antonini, 2003). The contents of these fractions will vary depending on the type of welding performed. Therefore, the potential exists for varying pulmonary effects for different welding processes. In addition, extrapulmonary effects of welding have been described including an increased risk for cardiovascular disease (Hilt et al., 1999, Ibfelt et al., 2010, Moulin et al., 1993, Newhouse et al., 1985, Sjogren et al., 2002, Suadicani et al., 2002). Supportingly, adverse cardiovascular effects in response to metal-rich particulate matter exposure, such as residual oil fly ash (Campen et al., 2000, Campen et al., 2002, Farraj et al., 2011, Kodavanti et al., 2002, Nurkiewicz et al., 2004, Watkinson et al., 1998), strengthen the likelihood of welding fume-induced systemic effects. In this study we compared three different welding fumes including manual metal arc stainless steel (MMA-SS), gas metal arc-SS (GMA-SS) or GMA-mild steel (GMA-MS). The MMA-SS welding fume contains soluble metals, primarily chromium, while the GMA-SS contains primarily insoluble metals that persist in the lung. The GMA-MS, a common welding fume used in industry and considered the least toxic of the three described here, also has limited solubility.

Recently we showed that pulmonary exposure to the engineered nanoparticle, carbon nanotubes (CNT), resulted in adverse cardiovascular effects (Erdely et al., 2009, Li et al., 2007, Simeonova and Erdely, 2009). Pulmonary exposure to CNT caused distressed aortic mitochondrial homeostasis and increased plaque lesion area in apolipoprotein E knockout mice which indicated systemic oxidative stress and inflammation (Li et al., 2007). Subsequent studies revealed a systemic inflammatory response, measured as blood gene expression, elevated serum cytokines and chemokines and vascular inflammation (Erdely et al., 2009). These data demonstrated a lung and systemic crosstalk in response to the exposure illustrating that indirect, pulmonary-derived inflammation contributed significantly to cardiovascular effects. Here, similar methodology as our CNT study was applied to investigate the differences between the systemic inflammatory responses of three welding fumes. Also, in anticipation of systemic effects, various parameters of pulmonary inflammation and toxicity were examined to yield mechanistic insight into these effects.

Section snippets

Animals and exposure conditions

Male C57BL/6 mice (Jackson Laboratory, Bar Harbor, ME) 10–12 weeks of age were used in this study. All mice were provided food (Teklad 7913) and tap water ad libitum in ventilated cages in a controlled humidity and temperature environment with a 12 h light/dark cycle. Animal care and use procedures were conducted in accordance with the “PHS Policy on Humane Care and Use of Laboratory Animals” and the “Guide for the Care and Use of Laboratory Animals” (NIH publication 86-23, 1996). These

Metal translocation

Following pulmonary exposure to welding fume there was rapid translocation of metals from the lung. The primary soluble component of the MMA-SS fume, chromium, was evident in the kidney (2.20 ± 0.38 μg/g PBS vs 13.87 ± 1.17* MMA-SS; *p < 0.05) and liver (2.51 ± 0.11 μg/g PBS vs 4.40 ± 0.46* MMA-SS; *p < 0.05) at 4 h post-exposure. Increased levels of manganese were found in the kidney after GMA-SS exposure (5.43 ± 0.24 μg/g PBS vs 7.56 ± 0.56* GMA-SS; *p < 0.05). There were no changes in other metals, including

Discussion

The findings of this study show that various types of welding fume result in different toxicities in the lung which thereby may influence systemic inflammation. While all fumes had increased pulmonary inflammatory gene expression within hours after exposure, the response was greater at 24 h in the SS fumes but not in the GMA-MS fume. In a corresponding fashion the SS fumes showed evidence of systemic inflammation. Interestingly, only the MMA-SS fume was able to induce stress response genes in

Conflict of interest

There are none.

Acknowledgements

Special thanks to Dr. Vincent Castranova, Dr. Jane Ma and Dr. Paul Nicolaysen for their review of the manuscript.

References (43)

  • M.J. Campen et al.

    Cardiac and thermoregulatory toxicity of residual oil fly ash in cardiopulmonary-compromised rats

    Inhal. Toxicol.

    (2000)
  • M.J. Campen et al.

    Cardiac and thermoregulatory effects of instilled particulate matter-associated transition metals in healthy and cardiopulmonary-compromised rats

    J. Toxicol. Environ. Health A

    (2002)
  • P. Coyle et al.

    Metallothionein: the multipurpose protein

    Cell. Mol. Life Sci.

    (2002)
  • D.W. Dockery et al.

    An association between air pollution and mortality in six U.S. cities

    N. Engl. J. Med.

    (1993)
  • C.M. Dollery et al.

    TIMP-4 is regulated by vascular injury in rats

    Circ. Res.

    (1999)
  • A. Erdely et al.

    Cross-talk between lung and systemic circulation during carbon nanotube respiratory exposure. Potential biomarkers

    Nano Lett.

    (2009)
  • S.C. Fang et al.

    Vascular function, inflammation, and variations in cardiac autonomic responses to particulate matter among welders

    Am. J. Epidemiol.

    (2009)
  • A.K. Farraj et al.

    ST depression, arrhythmia, vagal dominance, and reduced cardiac micro-RNA in particulate-exposed rats

    Am. J. Respir. Cell Mol. Biol.

    (2011)
  • D.R. Gold et al.

    Ambient pollution and heart rate variability

    Circulation

    (2000)
  • B. Hilt et al.

    Morbidity from ischemic heart disease in workers at a stainless steel welding factory

    Norsk. Epidemiol.

    (1999)
  • E. Ibfelt et al.

    Exposure to metal welding fume particles and risk for cardiovascular disease in Denmark: a prospective cohort study

    Occup. Environ. Med.

    (2010)
  • Cited by (25)

    • Metal enriched quasi-ultrafine particles from stainless steel gas metal arc welding induced genetic and epigenetic alterations in BEAS-2B cells

      2021, NanoImpact
      Citation Excerpt :

      Zeidler-Erdely et al. (2010a), in their comprehensive transcriptional profiling, also revealed differences in the DRG and gene networks triggered by WF according to mouse strains: gene expression was more deregulated in the susceptible A/J strain, and exposure to WF-emitted by GMAW-SS was associated with overexpression of immunomodulatory genes. Erdely et al. (2011) reported some DRG closely involved in inflammation (e.g., TNF-α, IL1-β), stress (e.g., HMOX, NQO1), coagulation, adhesion, and remodeling/growth factors in mice exposed to WF, but with some difference according to their emission by MMA-SS, GMAW-SS, and GMAW-MS. Moreover, Falcone et al. (2018a), exposing mice to WF emitted by GMAW-SS supported the above-mentioned results and the differential inflammatory and/or stress responses elicited depending on the type of WF. Oh et al. (2012), exposing rats to WF emitted by MMA-SS, also reported DRG profiles related to inflammation and repair processes, rapidly, dynamically, and stringently regulated in many biological diseases and pathological processes.

    • Altered ion transport in normal human bronchial epithelial cells following exposure to chemically distinct metal welding fume particles

      2017, Toxicology and Applied Pharmacology
      Citation Excerpt :

      Thus, the presence of soluble Cr and/or Ni cannot per se be the sole determinant of whether ion transport is stimulated by fume particles, but potency was increased by the presence of these metals. This finding supports those of Erdely et al. (2011), who also considered insoluble components of welding fume to contribute to their cytotoxic effects. A strong relationship exists between the presence of soluble Cr and Ni in fume particles and the observed decline in transepithelial resistance, inasmuch as MMA-SS caused a dose-related decline in Rt, whereas Rt was not affected at any dose of GMA-MS. As well, the decreases in Rt followed the same dose-relationship as the release of LDH from the cells.

    • IL-6, a central acute-phase mediator, as an early biomarker for exposure to zinc-based metal fumes

      2016, Toxicology
      Citation Excerpt :

      Welding fumes contain a wide range of metals and non-metals with varying toxic effects (Antonini, 2003; Antonini et al., 2003; Erdely et al., 2011).

    • Compositional variations in metal nanoparticle components of welding fumes impact lung epithelial cell toxicity

      2023, Journal of Toxicology and Environmental Health - Part A: Current Issues
    View all citing articles on Scopus
    1

    Deceased.

    View full text