Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Meade BJ [original query] |
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Legislation and other legal issues relevant in choosing to partner with a service dog in the workplace
Glenn MK , Foreman AM , Shahan KM , Meade BJ , Wirth O , Thorne KL . J Rehabil 2017 83 (2) 17-26 Objective. Decisions to use a service dog for employment impacts more than just the workplace. It extends into housing, transportation, and public access. Findings from an exploratory study of the use of service dogs in the workplace revealed a need for clarification and dissemination of relevant laws and resulting regulations associated with living and working with a service dog (Glenn, 2013). This investigation sought to respond with a review of legislation and case law that may impact a person's ability to live and work independently with a service dog. Method. A search of the regulations and case law in the United States related to the use of a service dog in various environments was conducted, focusing on examples of legal precedents that have arisen at the federal, state and local levels. Results. Federal law and resulting regulations, as well as local and state case law, were presented for Disability Support and Accommodation: service animal definitions, use of service animals in different environments to include housing, public access, transportation, and employment, rights to privacy, and responsibility to maintain control of the dog. Conclusions. Two themes needing attention emerged: (1) discrepant interpretations of service animal in the law and by the general population and (2) among service dog handlers and allies there exists a lack of accurate information and ability to inform others of their rights, the laws and associated requirements related to service dog teams. |
Dogs in the workplace: a review of the benefits and potential challenges
Foreman AM , Glenn MK , Meade BJ , Wirth O . Int J Environ Res Public Health 2017 14 (5) Pet dogs, therapy dogs, and service dogs can be seen in workplaces with increasing frequency. Although dogs may provide many benefits to employees and employers, their presence may introduce additional hazards and concerns to the work environment. Therefore, decisions to accept dogs in the workplace may include many considerations including the health, safety, and well-being of employees, legal and cultural sensitivities, and animal welfare. The present paper serves to introduce the issue of dogs in the workplace and outline the potential benefits and challenges to their presence. The legal accommodations afforded to certain types of dogs in workplace settings are discussed, and the research findings pertaining to the potential benefits of dogs on human health and well-being are summarized. The paper concludes with considerations for human resource management personnel in the areas of diversity, employee relations, ethics and corporate responsibility, organizational and employee development, safety and security, and legal considerations, as well as suggested topics for future research. |
Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride
Anderson SE , Shane H , Long C , Lukomska E , Meade BJ , Marshall NB . J Immunotoxicol 2016 13 (4) 1-10 Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625-1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE + B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4 + T-cells, CD8 + T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8 + T-cells and CD86 + B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. |
A Role for Regulatory T Cells in a Murine Model of Epicutaneous Toluene Diisocyanate Sensitization
Long CM , Marshall NB , Lukomska E , Kashon ML , Meade BJ , Shane H , Anderson SE . Toxicol Sci 2016 152 (1) 85-98 Toluene diisocyanate (TDI) is a leading cause of chemical-induced occupational asthma which impacts workers in a variety of industries worldwide. Recently, the robust regulatory potential of regulatory T cells (Tregs) has become apparent, including their functional role in the regulation of allergic disease; however, their function in TDI-induced sensitization has not been explored. To elucidate the kinetics, phenotype, and function of Tregsduring TDI sensitization, BALB/c mice were dermally exposed (on each ear) to a single application of TDI (0.5-4% v/v) or acetone vehicle and endpoints were evaluated via RT-PCR and flow cytometry. The draining lymph node (dLN) Tregpopulation expanded significantly 4, 7, and 9 days after single 4% TDI exposure. This population was identified using a variety of surface and intracellular markers and was found to be phenotypically heterogeneous based on increased expression of markers including CD103, CCR6, CTLA4, ICOS, and Neuropilin-1 during TDI sensitization. Tregsisolated from TDI-sensitized mice were significantly more suppressive compared to their control counterparts, further supporting a functional role for Tregsduring TDI sensitization. Lastly, Tregswere depleted prior to TDI sensitization and an intensified sensitization response was observed. Collectively, these data indicate that Tregsexhibit a functional role during TDI sensitization. Because the role of Tregsin TDI sensitization has not been previously elucidated, these data contribute to the understanding of the immunologic mechanisms of chemical induced allergic disease. |
Investigations into the immunotoxicity and allergic potential induced by topical application of N-Butylbenzenesulfonamide (NBBS) in a murine model
Marrocco A , Meade BJ , Long CM , Lukomska E , Marshall NB , Anderson SE . J Toxicol Environ Health A 2015 78 (17) 1-11 N-Butylbenzene sulfonamide (NBBS) is a commonly used plasticizer found in numerous products. Due to its extensive use, lack of adequate toxicological data, and suspicion of toxicity based on the presence of structural alerts, it was nominated to the National Toxicology Program for comprehensive toxicological testing. The purpose of this study was to evaluate the potential for hypersensitivity and immune suppression following dermal exposure to NBBS using a murine model. NBBS tested negative in a combined irritancy/local lymph node assay (LLNA), classifying it as nonirritating and nonsensitizing. To estimate the immunosuppressive potential of NBBS, assays that assessed immunotoxicity were performed, including the immumnoglobulin (Ig) M response to T-cell-dependent antigen sheep red blood cells (SRBC), using the plaque-forming cell (PFC) assay and immune cell phenotyping. After a 28-d treatment with NBBS, mice exposed to the lowest concentration (25% NBBS) showed a significant increase in IgM-producing B cells in the spleen. No marked changes were identified in immune cell markers in the lymph node. In contrast to body weight, a significant elevation in kidney and liver weight was observed following dermal exposure to all concentrations of NBBS. These results demonstrate that dermal exposure to NBBS, other than liver and kidney toxicity, did not apparently induce immunotoxicity in a murine model. |
Selecting quality service dogs (part 1): morphological and health considerations
Parenti L , Wilson M , Foreman AM , Wirth O , Meade BJ . APDT Chron Dog 2015 2015 71-77 Service dogs include dogs for mobility, vision, hearing, developmental disabilities, diabetic alert, seizure alert, and psychiatric support. They are trained to "provide work or perform tasks related to an individual's disability." When accompanied by a service dog, the individual with a disability is afforded some public access protections (Parenti, Foreman, Meade, and Wirth, 2013). Current demand for service dogs outweighs supply (M. Winkle, Crowe, and Hendrix, 2012), and average wait times of up to three years for a well-trained dog are not uncommon. Service dogs are generally trained for a minimum of 18 months, and training can cost anywhere from $10,000 to $20,000 (Allen and Blascovich, 1996. According to some estimates, only 50% of dogs entering training progress to the level of service dog (Batt, Batt, Baguley, and McGreevy, 2008), increasing the cost of training and limiting the number of available dogs. Hereditary diseases and behavioral problems are the most common reasons for a dog to be released from a training program (Wahl, Herbst, Tsai, and Murphy, 2008). Targeted selection and breeding of physically and behaviorally healthy dogs would allow organizations to allocate their resources more efficiently, reduce training costs, and increase the supply of service dogs to those in need. Service dog training programs nationwide can benefit from selecting and breeding dogs based on characteristics relevant to their service dog specialty. This is the first of three articles on the selection and breeding of dogs for service work. The current article addresses morphological and health considerations; the remaining articles will focus on behavior and temperament characteristics and research in the field of service dog training. |
APDT research spotlight: project Rover's survey of assistance dog providers
Baughman P , Foreman A , Parenti L , Scotti JR , Meade BJ , Wilson ME , Wirth O . APDT Chron Dog 2015 2015 25-30 With the increasing demand for assistance dogs by individuals with physical and/or psychiatric disabilities (Nondiscrimination on the Basis of disability in State and Local Government Services, 2010), rapid growth is expected in the number of provider organizations that acquire, breed, train, and place dogs with individuals with disabilities. Unfortunately, there is a lack of information about this burgeoning service industry. For example, little is known about how many providers exist, the populations served by these organizations, the breeds of dogs used, and the specific tasks the dogs are trained to perform. To address these and other questions, a web-based survey of assistance dog provider organizations was conducted. This survey is part of Project ROVER (Returning Our Veterans to employment and Reintegration) which is a research collaboration between the National Institute for Occupational Safety and Health (NIOSH) and West Virginia University (WVU). The focus of Project ROVER is on the role that pets and assistance dogs may play in helping U.S. veterans reintegrate into civilian life and return to work. One objective is to obtain more information about how service dogs are aiding this process for veterans with disabilities. Psychiatric service dogs are of particular interest because veterans with post-traumatic stress disorder (PTSD) have lower rates of employment (Chan, Cheadle, Reiber, Untzer and Chaney, 2009) and service dogs for psychiatric disabilities are increasing in number (Smith, Esnayre and Love, 2003). A preliminary review of the professional literature and other media reports on assistance dog organizations revealed an absence of information on organizational characteristics, the services offered, the populations served, the types and breeds of dogs used, and the supply of trained dogs. This information is lacking not only for organizations serving veterans, but also for organizations serving other populations. Therefore this survey targeted all types of assistance dog organizations, regardless of the populations served. |
Triclosan induces thymic stromal lymphopoietin in skin promoting Th2 allergic responses
Marshall NB , Lukomska E , Long CM , Kashon ML , Sharpnack DD , Nayak AP , Anderson KL , Meade BJ , Anderson SE . Toxicol Sci 2015 147 (1) 127-39 Triclosan is an antimicrobial chemical incorporated into many personal, medical and household products. 75% of the U.S. population has detectable levels of triclosan in their urine and although it is not typically considered a contact sensitizer, recent studies have begun to link triclosan exposure with augmented allergic disease. We examined the effects of dermal triclosan exposure on the skin and lymph nodes of mice and in a human skin model to identify mechanisms for augmenting allergic responses. Triclosan (0-3%) was applied topically at 24 hour intervals to the ear pinnae of OVA-sensitized BALB/c mice. Skin and draining lymph nodes were evaluated for cellular responses and cytokine expression over time. The effects of triclosan (0-0.75%) on cytokine expression in a human skin tissue model was also examined. Exposure to triclosan increased the expression of TSLP, IL-1beta and TNF-alpha in the skin with concomitant decreases in IL-25, IL-33 and IL-1alpha. Similar changes in TSLP, IL1B and IL33 expression occurred in human skin. Topical application of triclosan also increased draining lymph node cellularity consisting of activated CD86+GL-7+ B cells, CD80+CD86+ dendritic cells, GATA-3+OX-40+IL-4+IL-13+ Th2 cells and IL-17A+ CD4 T cells. In-vivo antibody blockade of TSLP reduced skin irritation, IL-1beta expression, lymph node cellularity, and Th2 responses augmented by triclosan. Repeated dermal exposure to triclosan induces TSLP expression in skin tissue as a potential mechanism for augmenting allergic responses. |
Investigations of immunotoxicity and allergic potential induced by topical application of triclosan in mice
Anderson SE , Meade BJ , Long CM , Lukomska E , Marshall NB . J Immunotoxicol 2015 13 (2) 1-8 Triclosan is an antimicrobial chemical commonly used occupationally and by the general public. Using select immune function assays, the purpose of these studies was to evaluate the immunotoxicity of triclosan following dermal exposure using a murine model. Triclosan was not identified to be a sensitizer in the murine local lymph node assay (LLNA) when tested at concentrations ranging from 0.75-3.0%. Following a 28-day exposure, triclosan produced a significant increase in liver weight at concentrations of ≥ 1.5%. Exposure to the high dose (3.0%) also produced a significant increase in spleen weights and number of platelets. The absolute number of B-cells, T-cells, dendritic cells and NK cells were significantly increased in the skin draining lymph node, but not the spleen. An increase in the frequency of dendritic cells was also observed in the lymph node following exposure to 3.0% triclosan. The IgM antibody response to sheep red blood cells (SRBC) was significantly increased at 0.75% - but not at the higher concentrations - in the spleen and serum. These results demonstrate that dermal exposure to triclosan induces stimulation of the immune system in a murine model and raise concerns about potential human exposure. |
Potential health effects associated with dermal exposure to occupational chemicals
Anderson SE , Meade BJ . Environ Health Insights 2014 8 51-62 There are a large number of workers in the United States, spanning a variety of occupational industries and sectors, who are potentially exposed to chemicals that can be absorbed through the skin. Occupational skin exposures can result in numerous diseases that can adversely affect an individual's health and capacity to perform at work. In general, there are three types of chemical-skin interactions of concern: direct skin effects, immune-mediated skin effects, and systemic effects. While hundreds of chemicals (metals, epoxy and acrylic resins, rubber additives, and chemical intermediates) present in virtually every industry have been identified to cause direct and immune-mediated effects such as contact dermatitis or urticaria, less is known about the number and types of chemicals contributing to systemic effects. In an attempt to raise awareness, skin notation assignments communicate the potential for dermal absorption; however, there is a need for standardization among agencies to communicate an accurate description of occupational hazards. Studies have suggested that exposure to complex mixtures, excessive hand washing, use of hand sanitizers, high frequency of wet work, and environmental or other factors may enhance penetration and stimulate other biological responses altering the outcomes of dermal chemical exposure. Understanding the hazards of dermal exposure is essential for the proper implementation of protective measures to ensure worker safety and health. |
A revised taxonomy of assistance animals
Parenti L , Foreman A , Meade BJ , Wirth O . J Rehabil Res Dev 2013 50 (6) 745-756 The use of animals in various assistive, therapeutic, and emotional support roles has contributed to the uncoordinated expansion of labels used to distinguish these animals. To address the inconsistent vocabulary and confusion, this article proposes a concise taxonomy for classifying assistance animals. Several factors were identified to differentiate categories, including (1) whether the animal performs work or tasks related to an individual's disability; (2) the typical level of skill required by the animal performing the work or task; (3) whether the animal is used by public service, military, or healthcare professionals; (4) whether training certifications or standards are available; and (5) the existence of legal public access protections for the animal and handler. Acknowledging that some category labels have already been widely accepted or codified, six functional categories were identified: (1) service animal; (2) public service animal; (3) therapy animal; (4) visitation animal; (5) sporting, recreational, or agricultural animal; and (6) support animal. This taxonomy provides a clear vocabulary for use by consumers, professionals working in the field, researchers, policy makers, and regulatory agencies. |
Evaluation of the hypersensitivity potential of alternative butter flavorings
Anderson SE , Franko J , Wells JR , Lukomska E , Meade BJ . Food Chem Toxicol 2013 62C 373-381 Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3=17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25-50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. |
Toxicological analysis of limonene reaction products using an in vitro exposure system
Anderson SE , Khurshid SS , Meade BJ , Lukomska E , Wells JR . Toxicol In Vitro 2012 27 (2) 721-30 Epidemiological investigations suggest a link between exposure to indoor air chemicals and adverse health effects. Consumer products contain reactive chemicals which can form secondary pollutants which may contribute to these effects. The reaction of limonene and ozone is a well characterized example of this type of indoor air chemistry. The studies described here characterize an in vitro model using an epithelial cell line (A549) or differentiated epithelial tissue (MucilAir). The model is used to investigate adverse effects following exposure to combinations of limonene and ozone. In A549 cells, exposure to both the parent compounds and reaction products resulted in alterations in inflammatory cytokine production. A one hour exposure to limonene + ozone resulted in decreased proliferation when compared to cells exposed to limonene alone. Repeated dose exposures of limonene or limonene + ozone were conducted on MucilAir tissue. No change in proliferation was observed but increases in cytokine production were observed for both the parent compounds and reaction products. Factors such as exposure duration, chemical concentration, and sampling time point were identified to influence result outcome. These findings suggest that exposure to reaction products may produce more severe effects compared to the parent compound. |
Exposure to triclosan augments the allergic response to ovalbumin in a mouse model of asthma
Anderson SE , Franko J , Kashon ML , Anderson KL , Hubbs AF , Lukomska E , Meade BJ . Toxicol Sci 2012 132 (1) 96-106 During the last decade there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouth washes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75-3% (0.375-1.5 mg/mouse/day) for 28 consecutive days. Concordantly, mice were intraperitoneally injected with OVA (0.9 mcg) and aluminum hydroxide (0.5 mg) on days 1 and 10 and challenged with OVA (125 mcg) by pharyngeal aspiration on days 19 and 27. Compared to the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, Interleukin (IL)-13 cytokine levels, and lung eosinophils were demonstrated when mice were co-exposed to OVA and triclosan. Statistically significant increases in OVA-specific and non-specific airway hyperreactivity (AHR) were observed for all triclosan co-exposed groups when compared to the vehicle and OVA controls. In these studies exposure to triclosan alone was not demonstrated to be allergenic, however; co-exposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens. |
Immunotoxicity and allergic potential induced by topical application of dimethyl carbonate (DMC) in a murine model
Anderson SE , Franko J , Anderson KL , Munson AE , Lukomska E , Meade BJ . J Immunotoxicol 2012 10 (1) 59-66 Dimethyl carbonate (DMC) is an industrial chemical, used as a paint and adhesive solvent, with the potential for significant increases in production. Using select immune function assays, the purpose of these studies was to evaluate the immunotoxicity of DMC following dermal exposure using a murine model. Following a 28-day exposure, DMC produced a significant decrease in thymus weight at concentrations of 75% and greater. No effects on body weight, hematological parameters (erythrocytes, leukocytes, and their differentials), or immune cell phenotyping (B-cells, T-cells, and T-cell sub-sets) were identified. The IgM antibody response to sheep red blood cell (SRBC) was significantly reduced in the spleen but not the serum. DMC was not identified to be an irritant and evaluation of the sensitization potential, conducted using the local lymph node assay (LLNA) at concentrations ranging from 50-100%, did not identify increases in lymphocyte proliferation. These results demonstrate that dermal exposure to DMC induces immune suppression in a murine model and raise concern about potential human exposure and the need for occupational exposure regulations. |
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. |
Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin
Franko J , Meade BJ , Frasch HF , Barbero AM , Anderson SE . J Toxicol Environ Health A 2012 75 (1) 50-62 Recent data, using a murine model, have indicated that dermal exposure to perfluorooctanoic acid (PFOA) induces immune modulation, suggesting that this may be an important route of PFOA exposure. To investigate the dermal penetration potential of PFOA, serum concentrations were analyzed in mice following topical application. Statistically significant and dose-responsive increases in serum PFOA concentrations were identified. In vitro dermal penetration studies also demonstrated that PFOA permeates both mouse and human skin. Investigation into the mechanisms mediating PFOA penetration demonstrated that dermal absorption was strongly dependent upon the ionization status of PFOA. In addition, PFOA solid, but not 1% PFOA/acetone solution, was identified as corrosive using a cultured epidermis in vitro model. Despite its corrosive potential, expression of inflammatory cytokines in the skin of topically exposed mice was not altered. These data suggest that PFOA is dermally absorbed and that under certain conditions the skin may be a significant route of exposure. |
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. |
Potential immunotoxicological health effects following exposure to COREXIT 9500A during cleanup of the Deepwater Horizon oil spill
Anderson SE , Franko J , Lukomska E , Meade BJ . J Toxicol Environ Health A 2011 74 (21) 1419-30 Workers involved in the Deepwater Horizon oil spill cleanup efforts reported acute pulmonary and dermatological adverse health effects. These studies were undertaken to assess the immunotoxicity of COREXIT 9500A, the primary dispersant used in cleanup efforts, as a potential causative agent. COREXIT 9500A and one of its active ingredients, dioctyl sodium sulfosuccinate (DSS), were evaluated using murine models for hypersensitivity and immune suppression, including the local lymph node assay (LLNA), phenotypic analysis of draining lymph node cells (DLN), mouse ear swelling test (MEST), total serum immunoglobulin E (IgE), and the plaque-forming cell (PFC) assay. Dermal exposure to COREXIT 9500A and DSS induced dose-responsive increases in dermal irritation and lymphocyte proliferation. The EC3 values for COREXIT 9500A and DSS were 0.4% and 3.9%, respectively, resulting in a classification of COREXIT 9500A as a potent sensitizer and DSS as a moderate sensitizer. A T-cell-mediated mechanism underlying the LLNA was supported by positive responses in the MEST assay for COREXIT and DSS, indicated by a significant increase in ear swelling 48 h post challenge. There were no marked alterations in total serum IgE or B220+/IgE+ lymph-node cell populations following exposure to COREXIT 9500A. Significant elevations in interferon (IFN)-gamma but not interleukin (IL)-4 protein were also observed in stimulated lymph node cells. The absence of increases in IgE and IL-4 in the presence of enhanced lymphocyte proliferation, positive MEST responses, and elevations in IFN-gamma suggest a T-cell-mediated mechanism. COREXIT 9500A did not induce immunosuppression in the murine model. |
The LLNA: a brief review of recent advances and limitations
Anderson SE , Siegel PD , Meade BJ . J Allergy (Cairo) 2011 2011 424203 Allergic contact dermatitis is the second most commonly reported occupational illness, accounting for 10% to 15% of all occupational diseases. This highlights the importance of developing rapid and sensitive methods for hazard identification of chemical sensitizers. The murine local lymph node assay (LLNA) was developed and validated for the identification of low molecular weight sensitizing chemicals. It provides several benefits over other tests for sensitization because it provides a quantitative endpoint, dose-responsive data, and allows for prediction of potency. However, there are also several concerns with this assay including: levels of false positive responses, variability due to vehicle, and predictivity. This report serves as a concise review which briefly summarizes the progress, advances and limitations of the assay over the last decade. |
Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats
Anderson SE , Munson AE , Butterworth LF , Germolec D , Morgan DL , Roycroft JA , Dill J , Meade BJ . Inhal Toxicol 2009 22 (2) 125-32 1-Bromopropane (1-BP) is categorized as a high-production-volume chemical and is currently used in the manufacture of pharmaceuticals, pesticides, and other chemicals. Its usage is estimated to be around 5 million pounds per year, resulting in the potential for widespread exposure in the workplace. Case reports and animal studies have suggested exposure to this compound may cause adverse reproductive and neurological effects. Using a battery of immunological assays, the immunotoxicity of 1-BP after whole body inhalation exposure in both mice and rats was evaluated. Significant decreases in the spleen immunoglobulin (Ig) M response to sheep red blood cells (SRBC) were observed in both mice (125-500 ppm) and rats (1000 ppm) after exposure to 1-BP for 10 wk. In addition, total spleen cells and T cells were significantly decreased after approximately 4 wk of 1-BP exposure in both mice (125-500 ppm) and rats (1000 ppm). No change in natural killer (NK) cell activity was observed. The observed alterations in spleen cellularity, phenotypic subsets, and impairment of humoral immune function across species raise further concern about human exposure to 1-BP and demonstrate the need for additional investigations into potential adverse health effects. |
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