Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-7 (of 7 Records) |
Query Trace: Jackson LG[original query] |
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Systemic and immunotoxicity induced by topical application of perfluoroheptane sulfonic acid (PFHpS) or perfluorooctane sulfonic acid (PFOS) in a murine model
Weatherly LM , Shane HL , Jackson LG , Lukomska E , Baur R , Cooper MP , Anderson SE . J Immunotoxicol 2024 21 (1) 2371868 ![]() Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic surfactants of over 12,000 compounds that are incorporated into numerous products for their chemical and physical properties. Studies have associated PFAS with adverse health effects. Although there is a high potential for dermal exposure, these studies are lacking. The present study evaluated the systemic and immunotoxicity of subchronic 28- or 10-days of dermal exposure, respectively, to PFHpS (0.3125-2.5% or 7.82-62.5 mg/kg/dose) or PFOS (0.5% or 12.5 mg/kg/dose) in a murine model. Elevated levels of PFHpS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. PFHpS induced significantly increased relative liver weight, significantly decreased relative spleen and thymus weight, altered serum chemistries, and altered histopathology. Additionally, PFHpS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen of genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells and CD11b(+) monocyte and/or macrophages in the spleen along with decreases in eosinophils and dendritic cells in the skin. These findings support PFHpS absorption through the skin leading to liver damage and immune suppression. |
Systemic and immunotoxicity induced by topical application of perfluorohexane sulfonic acid (PFHxS) in a murine model
Weatherly LM , Shane HL , Jackson LG , Lukomska E , Baur R , Cooper MP , Anderson SE . Food Chem Toxicol 2024 186 114578 Per- and polyfluoroalkyl substances (PFAS) are a large group of stable synthetic surfactants that are incorporated into numerous products for their water and oil resistance and have been associated with adverse health effects. The present study evaluated the systemic and immunotoxicity of sub-chronic 28- or 10-day dermal exposure of PFHxS (0.625-5% or 15.63-125 mg/kg/dose) in a murine model. Elevated levels of PFHxS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. Liver weight (% body) significantly increased and spleen weight (% body) significantly decreased with PFHxS exposure, which was supported by histopathological changes. Additionally, PFHxS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen with genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells, NK cells, and CD11b(+) monocyte/macrophages in the spleen along with increases in CD4(+) and CD8(+) T-cells, NK cells, and neutrophils in the skin. These findings support dermal PFHxS-induced liver damage and immune suppression. Overall, data support PFHxS absorption through the skin and demonstrate immunotoxicity via this exposure route, suggesting the need for further examination. |
Irritancy and allergic responses induced by exposure to the indoor air chemical 4-oxopentanal
Anderson SE , Franko J , Jackson LG , Wells JR , Ham JE , Meade BJ . Toxicol Sci 2012 127 (2) 371-81 Over the last two decades, there has been an increasing awareness regarding the potential impact of indoor air pollution on human health. People working in an indoor environment often experience symptoms such as eye, nose and throat irritation. Investigations into these complaints have ascribed the effects, in part, to compounds emitted from building materials, cleaning/consumer products, and indoor chemistry. One suspect indoor air contaminant that has been identified is the dicarbonyl 4-oxopentanal (4-OPA). 4-OPA is generated through the ozonolysis of squalene and several high volume production compounds that are commonly found indoors. Following preliminary workplace sampling that identified the presence of 4-OPA, these studies examined the inflamatory and allergic responses to 4-OPA following both dermal and pulmonary exposure using a murine model. 4-OPA was tested in a combined local lymph node assay (LLNA) and identified to be an irritant and sensitizer. A Th1-mediated hypersensitivity response was supported by a positive response in the mouse ear swelling test (MEST). Pulmonary exposure to 4-OPA caused a significant elevation in nonspecific airway hyperreactivity, increased numbers of lung associated lymphocytes and neutrophils and increased interferon-gamma production by lung associated lymph nodes. These results suggest that both dermal and pulmonary exposure to 4-OPA may elicit irritant and allergic responses and may help to explain some of the adverse health effects associated with poor indoor air quality. |
The identification of a sensitizing component used in the manufacturing of an ink ribbon
Anderson SE , Tapp L , Durgam S , Meade BJ , Jackson LG , Cohen DE . J Immunotoxicol 2012 9 (2) 193-200 Skin diseases including dermatitis constitute approximately 30% of all occupational illnesses, with a high incidence in the printing industry. An outbreak of contact dermatitis among employees at an ink ribbon manufacturing plant was investigated by scientists from the National Institute for Occupational Safety and Health (NIOSH). Employees in the process areas of the plant were exposed to numerous chemicals and many had experienced skin rashes, especially after the introduction of a new ink ribbon product. To identify the causative agent(s) of the occupational dermatitis, the murine local lymph node assay (LLNA) was used to identify the potential of the chemicals used in the manufacture of the ink ribbon to induce allergic contact dermatitis. Follow-up patch testing with the suspected allergens was conducted on exposed employees. Polyvinyl butyral, a chemical component used in the manufacture of the ink ribbon in question and other products, tested positive in the LLNA, with an EC3 of 3.6%, which identifies it as a potential sensitizer; however, no employees tested positive to this chemical during skin patch testing. This finding has implications beyond those described in this report because of occupational exposure to polyvinyl butyral outside of the printing industry. |
Evaluation of furfuryl alcohol sensitization potential following dermal and pulmonary exposure: enhancement of airway responsiveness
Franko J , Jackson LG , Hubbs A , Kashon M , Meade BJ , Anderson SE . Toxicol Sci 2011 125 (1) 105-15 Furfuryl alcohol is considered by the United States Environmental Protection Agency to be a high volume production chemical with over 1 million pounds produced annually. Due to its high production volume and its numerous industrial and consumer uses there is considerable potential for work-related exposure, as well as exposure to the general population, through pulmonary, oral, and dermal routes of exposure. Human exposure data reports a high incidence of asthma in foundry mold workers exposed to furan resins, suggesting potential immunologic effects. Although furfuryl alcohol was nominated and evaluated for its carcinogenic potential by the National Toxicology Program, studies evaluating its immunotoxicity are lacking. The studies presented here evaluated the immunotoxic potential of furfuryl alcohol following exposure by the dermal and pulmonary routes using a murine model. When tested in a combined irritancy local lymph node assay (LLNA), furfuryl alcohol was identified to be an irritant and mild sensitizer (EC3 = 25.6%). Pulmonary exposure to 2% furfuryl alcohol resulted in enhanced airway hyperreactivity, eosinophilic infiltration into the lungs, and enhanced cytokine production (IL-4, IL-5 and IFN-gamma) by ex vivo stimulated lung-associated draining lymphoid cells. Airway hyperreactivity and eosinophilic lung infiltration were augmented by prior dermal exposure to furfuryl alcohol. These results suggest that furfuryl alcohol may play a role in the development of allergic airway disease and encourages the need for additional investigation. |
Evaluation of dicarbonyls generated in a simulated indoor air environment using an in vitro exposure system
Anderson SE , Jackson LG , Franko J , Wells JR . Toxicol Sci 2010 115 (2) 453-61 Over the last two decades, there has been increasing awareness regarding the potential impact of indoor air pollution on health. Exposure to volatile organic compounds (VOCs) or oxygenated organic compounds formed from indoor chemistry has been suggested to contribute to adverse health effects. These studies use an in vitro monitoring system called VitroCell, to assess chemicals found in the indoor air environment. The structurally similar dicarbonyls diacetyl, 4-oxopentanal (4-OPA), glyoxal, glutaraldehyde, and methyl glyoxal were selected for use in this system. The VitroCell module was used to determine whether these dicarbonyls were capable of inducing inflammatory cytokine expression by exposed pulmonary epithelial cells (A549). Increases in the relative fold change in mRNA expression of the inflammatory mediators, interleukin (IL)-6, interleukin (IL)-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha) were identified following exposure to diacetyl, 4-OPA, glyoxal, glutaraldehyde, and methyl glyoxal when compared to a clean air control. Consistent results were observed when the protein levels of these cytokines were analyzed. Exposure to 4-OPA significantly elevated IL-8, IL-6, GM-CSF and TNF-alpha while glutaraldehyde caused significant elevations in IL-6, IL-8 and TNF-alpha. IL-6 and IL-8 were also significantly elevated after exposure to diacetyl, glyoxal and methyl glyoxal. These studies suggest that exposure to structurally similar oxygenated reaction products may be contributing to some of the health effects associated with indoor environments and may provide an in vitro method for identification and characterization of these potential hazards. |
Irritancy and allergic responses induced by topical application of ortho-phthalaldehyde
Anderson SE , Umbright C , Sellamuthu R , Fluharty K , Kashon M , Franko J , Jackson LG , Johnson VJ , Joseph P . Toxicol Sci 2010 115 (2) 435-43 Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The Epiderm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125% and 0.55% OPA induced irritation, while gluteraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.005% to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. IgE-inducing potential was evaluated by phenotypic analysis of draining lymph node cells and measurement of total and specific serum IgE levels. The 0.1% and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG(1). In addition, significant increases in IL-4 mRNA and protein expression in the draining lymph nodes were observed in OPA treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde. |
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