ABSTRACT
BACKGROUND: Acrylic monomers (acrylates), methacrylates and cyanoacrylates all cause asthma by respiratory sensitization. Occupational inhalation exposures occur across a variety of industries including health care and dental work, beauty, laboratory science, assembly and plastic moulding. AIMS: To examine notifications of occupational asthma caused by acrylic compounds from a UK-based regional surveillance scheme, in order to highlight prevalent exposures and trends in presentation. METHODS: Retrospective review of all cases reported to the SHIELD surveillance scheme for occupational asthma, West Midlands, UK between 1989 and 2014. Patient data were gathered on demographics, employment, asthma symptoms and diagnostic investigations including serum immunological testing, serial peak flow analysis and specific inhalation challenge tests. Descriptive statistics were used to illustrate worker characteristics and evidence for sensitization to acrylic compounds. RESULTS: There were 20 affected patients out of 1790 total cases of occupational asthma (1%); all cases were confirmed by OASYS (Occupational Asthma SYStem) analysis of serial peak flow measurements, with three additional positive specific inhalation challenge tests. Three out of 20 (15%) patients were current smokers and 11/20 (55%) were atopic. A variety of exposures and industries were implicated including: manufacturing, health care, beauty and printing and a novel presentation seen in teachers exposed to floor adhesives. CONCLUSIONS: This is the largest reported series of occupational asthma caused by acrylic compounds, which remain an important aetiological factor in this disease. Exposure occurs in a variety of industries, particularly in manufacturing and is seen with other, perhaps better recognized sensitizing agents such as isocyanates and epoxy resins.
Subject(s)
Acrylates/toxicity , Asthma, Occupational/epidemiology , Adhesives/toxicity , Adult , Asthma, Occupational/chemically induced , Female , Humans , Inhalation Exposure/adverse effects , Male , Middle Aged , Peak Expiratory Flow Rate , Retrospective Studies , United Kingdom/epidemiologyABSTRACT
BACKGROUND: Cosmetic products are subject to the European Cosmetics Regulation: They shall not harm human health when used under "normal or reasonably foreseeable conditions". Hazardous cosmetic products are reported by the EU Member States to the EU Commission and are listed in the database of the European Rapid Alert System RAPEX. MATERIAL AND METHODS: The reports from Germany on dangerous cosmetic products from the years 2005-3/2017 in the European RAPEX database were systematically analyzed. RESULTS: During the study period, 157 dangerous cosmetic products were reported from Germany. The most common product categories were bleaching creams (24.2%) because of the content of hydroquinone, mercury or corticosteroids, creams/lotions/gels (10.8%) mainly due to microbiological contamination, henna products (10.2%) because of sensitizing concentrations of paraphenylene diamine, and nail adhesives (8.9%) because of high levels of methyl methacrylate. CONCLUSIONS: Hazardous cosmetic products appear to be rare in view of the high market volume of cosmetics, even though the total number of official investigations the RAPEX reports based on is not known. Dermatologists should inform the competent monitoring authorities in case of a suspected harm to health caused by dangerous cosmetic products so that the products can be examined and, if necessary, withdrawn from the market.
Subject(s)
Cosmetics/toxicity , Databases, Factual , Adhesives/toxicity , Bleaching Agents/toxicity , Germany , Glucocorticoids/toxicity , Humans , Hydroquinones/toxicity , Mercury/toxicity , Methylmethacrylate/toxicity , Naphthoquinones/toxicity , Phenylenediamines/toxicity , Skin Cream/adverse effectsABSTRACT
OBJECTIVE: The purpose of this study was to compare the cytotoxicity of four denture adhesives on human gingival fibroblast cells. MATERIALS AND METHODS: Immortalized human gingival fibroblasts were cultured with one of four different denture adhesives, Polident, Protefix, Staydent or Denfix-A, which was placed in insert dishes (10% w/v concentration) for 48 h. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and flow cytometric apoptosis assay were used to evaluate cell viability and apoptosis rates. The fibroblasts were also examined under a scanning electron microscope. RESULTS: The MTT assay showed that all denture adhesives resulted in a significantly lower cell viability compared to the control cells propagated in normal culture medium (p < 0.05), with Staydent demonstrating the lowest cell viability. According to the flow cytometric apoptosis assay, Staydent and Protefix showed significantly higher apoptosis rates than the control group (p < 0.05), whereas Polident and Denfix-A did not demonstrate any significant differences (p > 0.05). Staydent showed the highest apoptosis rate. Scanning electron microscopy showed that the cells of the Staydent group underwent cytoplasmic membrane shrinkage, with cell free areas containing residual fragments of the membrane of dead cells. CONCLUSIONS: The four denture adhesives evaluated in this study imparted cytotoxic effects on human gingival fibroblast cells. Staydent showed the highest toxicity.
Subject(s)
Adhesives/toxicity , Denture Retention , Fibroblasts/drug effects , Gingiva/cytology , Apoptosis/drug effects , Cell Culture Techniques , Cell Line , Cell Membrane/drug effects , Cell Shape/drug effects , Cell Survival/drug effects , Flow Cytometry , Gingiva/drug effects , Humans , Maleates/toxicity , Microscopy, Electron, Scanning , Polyethylenes/toxicity , Tetrazolium Salts , Thiazoles , Time FactorsABSTRACT
BACKGROUND: To date, there have been very little data on the cytotoxic responses of different cell lines to denture adhesives. OBJECTIVE: To determine the cytotoxicity of three denture adhesives on primary human oral keratinocytes (HOKs), fibroblasts (HOFs) and permanent mouse fibroblasts cell lines (L929). METHODS: Three commercial denture adhesives (two creams and one powder) were prepared for indirect contact using the agar diffusion test, as well as extracts in MTT assay. The results of the MTT assay were statistically analysed by one-way anova and Tukey's test (p < 0.05). RESULTS: All of the tested denture adhesives showed mild to moderate cytotoxicity to primary HOKs (p < 0.001), whereas none of three was toxic to L929 cells (p > 0.05) in both assays. For primary HOFs cultures, slight cytotoxicity was observed for one of the products from the agar diffusion test and undiluted eluates of all tested adhesives with MTT assay (p < 0.01). CONCLUSION: Denture adhesives are toxic to the primary HOKs and HOFs cultures, whereas non-toxic to L929 cells. The results suggest that primary human oral mucosal cells may provide more valuable information in toxicity screening of denture adhesives.
Subject(s)
Adhesives/toxicity , Denture Retention , Fibroblasts/drug effects , Gingiva/cytology , Keratinocytes/drug effects , Mouth Mucosa/cytology , Alginates/toxicity , Animals , Carboxymethylcellulose Sodium/toxicity , Cell Line , Cell Survival/drug effects , Cells, Cultured , Coloring Agents , Gingiva/drug effects , Glucuronic Acid/toxicity , Hexuronic Acids/toxicity , Humans , Maleates/toxicity , Mice , Mouth Mucosa/drug effects , Polyethylenes/toxicity , Tetrazolium Salts , ThiazolesABSTRACT
A number of neurotoxic chemicals induce accumulation of neurofilaments in axonal swellings that appear at varying distances from the cell body. This pathology is associated with axonal degeneration of different degrees. The clinical manifestation is most commonly that of a mixed motor-sensory peripheral axonopathy with a disto-proximal pattern of progression, as in cases of chronic exposure to n-hexane and carbon disulphide. It has been demonstrated that protein adduct formation is a primary molecular mechanism of toxicity in these axonopathies, but how this mechanism leads to neurofilament accumulation and axonal degeneration remains unclear. Furthermore, little is known regarding the mechanisms of neurofilamentous axonopathy caused by 3,3'-iminodipropionitrile, an experimental toxin that induces proximal axon swelling that is strikingly similar to that found in early amyotrophic lateral sclerosis. Here, we review the available data and main hypotheses regarding the toxic axonopathies and compare them with the current knowledge of the biological basis of neurofilament transport. We also review recent studies addressing the question of how these axonopathies may cause axonal degeneration. Understanding the mechanisms underlying the toxic axonopathies may provide insight into the relationship between neurofilament behaviour and axonal degeneration, hopefully enabling the identification of new targets for therapeutic intervention. Because neurofilament abnormalities are a common feature of many neurodegenerative diseases, advances in this area may have a wider impact beyond toxicological significance.
Subject(s)
Adhesives/toxicity , Amyotrophic Lateral Sclerosis/chemically induced , Axons/drug effects , Carbon Disulfide/toxicity , Hexanes/toxicity , Neurofilament Proteins/drug effects , Nitriles/toxicity , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/pathology , Axons/metabolism , Axons/pathology , Humans , Neurofilament Proteins/metabolism , Neurotoxins/toxicityABSTRACT
CONTEXT: Recent technological advances allow ventilation holes in (or adjacent to) cigarette filters to be produced using lasers instead of using the mechanical procedures of earlier techniques. OBJECTIVE: Analytical chemistry can be used to compare the composition of mainstream smoke from experimental cigarettes having filters with mechanically produced ventilation holes to that of cigarettes with ventilation holes that were produced using laser technology. MATERIALS AND METHODS: Established procedures were used to analyze the smoke composition of 38 constituents of mainstream smoke generated using standard conditions. RESULTS: There were no differences between the smoke composition of cigarettes with filter ventilation holes that were produced mechanically or through use of laser technology. CONCLUSION: The two methods for producing ventilation holes in cigarette filters are equivalent in terms of resulting mainstream smoke chemistry, at two quite different filter ventilation percentages.
Subject(s)
Air Filters , Cellulose/analogs & derivatives , Consumer Product Safety , Nicotiana/chemistry , Smoke/analysis , Tobacco Industry/methods , Tobacco Products/analysis , Adhesives/chemistry , Adhesives/toxicity , Cellulose/chemistry , Cellulose/toxicity , Flax/chemistry , Flax/toxicity , Lasers , Materials Testing , Paper , Plasticizers/chemistry , Plasticizers/toxicity , Smoke/adverse effects , Surface Properties , Nicotiana/toxicity , Tobacco Industry/instrumentation , Tobacco Products/toxicity , Triacetin/chemistry , Triacetin/toxicityABSTRACT
CONTEXT: Adhesives are used in several different manufacturing operations in the production of cigarettes. The use of new, "high-speed-manufacture" adhesives (e.g. vinyl acetate based) could affect the smoke chemistry and toxicology of cigarettes, compared with older "low-speed-manufacture" adhesives (e.g. starch based). OBJECTIVE: This study was conducted to determine whether the inclusion of different levels of three adhesives (ethylene vinyl acetate, polyvinyl acetate and starch) in experimental cigarettes results in different smoke chemistry and toxicological responses in in vitro and in vivo assays. MATERIALS AND METHODS: A battery of tests (analytical chemistry, in vitro and in vivo assays) was used to compare the chemistry and toxicology of smoke from experimental cigarettes made with different combinations of the three adhesives. Varying levels of the different side-seam adhesives, as well as the transfer of adhesives from packaging materials, were tested. RESULTS: There were differences in some mainstream cigarette smoke constituents as a function of the level of adhesive added to experimental cigarettes and between the tested adhesives. None of these differences translated into statistically significant differences in the in vitro or in vivo assays. CONCLUSION: The use of newer "high-speed-manufacture" vinyl acetate-based adhesives in cigarettes does not produce toxicological profiles that prevent the adhesives from replacing the older "low-speed-manufacture" adhesives (such as starch).
Subject(s)
Adhesives/toxicity , Consumer Product Safety , Polyvinyls/toxicity , Smoke/adverse effects , Tobacco Products/toxicity , Adhesives/chemistry , Animals , BALB 3T3 Cells , Cell Survival/drug effects , Female , Hyperplasia , Inhalation Exposure/adverse effects , Male , Materials Testing , Mice , Mutagenicity Tests , Mutagens/analysis , Mutagens/chemistry , Mutagens/toxicity , Polyvinyls/chemistry , Product Packaging , Rats, Sprague-Dawley , Respiratory Mucosa/drug effects , Respiratory Mucosa/pathology , Smoke/analysis , Specific Pathogen-Free Organisms , Starch/chemistry , Starch/toxicity , Nicotiana/chemistry , Nicotiana/toxicity , Tobacco Products/analysis , Toxicity TestsABSTRACT
CONTEXT: Cigarettes often have a small identifying mark (monogram) printed either on the cigarette paper toward the filter end of the cigarette or on the tipping paper. OBJECTIVE: A battery of tests was used to compare the toxicology of mainstream smoke from experimental cigarettes manufactured with different monogram inks. Cigarettes with different concentrations of different pigments were compared with cigarettes without ink, and with a control ink. MATERIALS AND METHODS: Smoke from each of the experimental cigarettes was evaluated using analytical chemistry and in vitro bacterial mutagenicity (Salmonella, five strains, ± S9) and cytotoxicity (neutral red uptake) assays. RESULTS: No differences were observed between experimental cigarettes printed with three different pigment loads of iron oxide-based Black pigment and non-printed cigarettes. In general, no dose response was observed. However, increases in certain smoke constituents were found to correlate with Pigment Yellow 14 (also known as benzidine yellow) and Pigment Blue 15 (copper phthalocyanine). Increases in bacterial mutagenicity were observed for high-level print of Pigment Yellow 14 in TA98 and TA1537 and the high-level print of Pigment Blue 15 in TA98. In vitro cytotoxicity of mainstream smoke was unaffected by the presence of monogram ink on cigarettes. CONCLUSION: Statistically significant dose-responsive constituent changes and an increase in mutagenicity were observed with inclusion of Pigment Yellow 14 and Pigment Blue 15. Other pigments showed minimal toxicological activity.
Subject(s)
Coloring Agents/toxicity , Consumer Product Safety , Ink , Smoke/adverse effects , Tobacco Products/toxicity , Adhesives/chemistry , Adhesives/toxicity , Air Filters , Animals , BALB 3T3 Cells , Cell Survival/drug effects , Cellulose/analogs & derivatives , Cellulose/chemistry , Cellulose/toxicity , Coloring Agents/chemistry , Lethal Dose 50 , Linseed Oil/chemistry , Linseed Oil/toxicity , Materials Testing , Mice , Mutagenicity Tests , Mutagens/analysis , Mutagens/chemistry , Mutagens/toxicity , Paper , Resins, Plant/chemistry , Resins, Plant/toxicity , Smoke/analysis , Nicotiana/chemistry , Nicotiana/toxicity , Tobacco Products/analysis , Toxicity TestsABSTRACT
BACKGROUND: A 43-year-old woman was referred by her occupational health service with suspected occupational contact dermatitis. In connection with the investigation, a workplace visit was undertaken at her company, which used an adhesive based on pre-polymeric diphenylmethane diisocyanate in one of its units. During the visit, we became aware of six other employees with skin problems who were then referred to our department for investigation. OBJECTIVES: To investigate the seven employees complaining about skin problems. METHODS: Seven employees were patch tested with a baseline series, an isocyanate series, and a series with work material. RESULTS: Five of seven patients had occupational contact allergy. Four reacted to isocyanate-related test preparations, and one to a cleanser used at the workplace. CONCLUSIONS: Workplace visits constitute an important part of an occupational investigation, as they might give a broader picture of the problems at a company. In this case, it was found that 5 of 100 employees currently had or had previously had occupation-related skin problems. Owing to 'healthy worker selection', some of these patients might have been missed if we had not performed a full-scale workplace visit.
Subject(s)
Adhesives/toxicity , Dermatitis, Allergic Contact/etiology , Dermatitis, Occupational/etiology , Isocyanates/toxicity , Adult , Female , Humans , Middle Aged , Occupational Medicine/methods , Patch Tests , WorkplaceABSTRACT
BACKGROUND: Eyelash extensions are applied on top of customers' lashes using instant glue containing cyano acrylate, known to cause occupational rhinitis (OR) and occupational asthma (OA). The number of beauty professionals applying these extensions is increasing due to their popularity. AIMS: To report on a case of OA with OR and a case of OR attributable to lash extension glue and to evaluate respiratory exposure in lash extension work. METHODS: Two beauty professionals with suspected OA and/or OR underwent inhalation challenge, including both control challenge and work-mimicking challenges using the lash extension glue, each with a 24-h follow-up. Volatile organic compounds (VOCs) present were assessed during the lash extension glue challenge. The glues were analysed for their (meth)acrylate content. RESULTS: Both beauty professionals (case 1 and case 2) applied lash extensions regularly for several hours per day as part of their work and had work-related rhinitis. Case 1 had a longer history of lash extension work and also had asthmatic symptoms. The first lash extension glue challenge was negative in both cases, but positive OR reactions were detected in the second test. Case 1 also had a late asthmatic reaction. During the lash extension glue challenge, VOC were present in total concentrations below the irritant threshold and ethylcyanoacrylate (ECA) was detected in a concentration of 0.4mg/m(3). Chemical analysis of the glues revealed ECA was the major component. CONCLUSIONS: Application of eyelash extensions using small amounts of cyanoacrylate-based glues can cause OA and OR.
Subject(s)
Adhesives/toxicity , Asthma, Occupational/chemically induced , Beauty Culture , Cyanoacrylates/toxicity , Rhinitis/chemically induced , Adult , Eyelashes , Female , Humans , Young AdultABSTRACT
Adhesives are commonly used by denture wearers to increase the retention and stability of the complete denture, to improve the chewing and masticatory abilities and to psychologically support the patient to make the complete denture more acceptable. Denture fixatives can be especially recommended for use and to aid retention for patients with dryness of the mouth, poor secretion of saliva and xerostomia (e.g. diabetes mellitus). Dental adhesives may be contaminated with bacteria, yeast and fungi during the manufacturing process, and they have been shown to initiate and promote microbial growth. Some products have been shown to release formaldehyde, which is cytotoxic to cell culture and fibroblasts and is a potent allergen. Patients with chronic xerostomia may use denture adhesives during the course of the treatment and disease. These patients are often immunocompromised, and microorganisms they are exposed to must be considered potential pathogens.
Subject(s)
Adhesives , Denture Retention , Denture, Complete , Xerostomia/physiopathology , Adhesives/chemistry , Adhesives/toxicity , Bacteria/growth & development , Bacteria/pathogenicity , Chronic Disease , Denture, Complete/microbiology , Denture, Complete/psychology , Drug Contamination , Formaldehyde/chemistry , Formaldehyde/toxicity , Humans , Immunocompromised Host , Mouth/microbiology , Saliva/metabolism , Secretory Rate/physiologyABSTRACT
BACKGROUND: The warm und humid environment, friction and occlusion within shoes make the feet to a favorable body site to acquire allergic contact dermatitis. OBJECTIVES: To evaluate and compare patch test results in patients with suspected contact allergy of the feet with the results in those with concomitant involvement of the feet/legs, feet/hands, and all others tested (excluding secondary involvement of the feet in 'others'), with regard to specific patterns of clinical data and patch test results. METHODS: For the present cross-sectional study, data were collected by the 59 participating centres of the Information Network of Departments of Dermatology in Germany, Austria, and Switzerland, including 102 209 patients patch-tested between January 2001 and December 2010. RESULTS: Allergens that were significantly over-represented in the tested 2671 foot patients included potassium dichromate, colophonium, and p-tert-butylphenol-formaldehyde resin. Among materials brought in by the patients, shoe pieces (27.5%), topical medications/pharmaceutical products (24.4%) and cosmetics (16.8%) played a major role. The final diagnoses of vesicular and hyperkeratotic dermatitis, as well as psoriasis, were significantly more common among foot patients. CONCLUSIONS: Chromium compounds and adhesives were the most common causes of allergic contact dermatitis among our foot patients. Psoriasis should be considered, particularly when the hands are concomitantly affected.
Subject(s)
Dermatitis, Allergic Contact/diagnosis , Foot Dermatoses/diagnosis , Patch Tests/methods , Adhesives/toxicity , Adult , Aged , Allergens , Chromium Compounds/toxicity , Cross-Sectional Studies , Dermatitis, Occupational/diagnosis , Female , Humans , Male , Middle Aged , Retrospective Studies , Shoes/adverse effectsABSTRACT
A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic elastomer, styrene-isoprene-styrene (SIS) block copolymer, in combination with tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin was selected as the model drug. The drug percutaneous absorption, adhesion properties, and skin irritation were investigated. The results suggested that the diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous absorption. [SI] content in SIS and SIS proportions put important effects on drug penetration and adhesion properties. The chemical enhancers had strong interactions with the matrix and gave small effect on enhancement of drug skin permeation. The in vivo absorption of samples showed low drug plasma peaks and a steady and constant plasma level for a long period. These results suggested that the possible side effects of drug were attenuated, and the pharmacological effects were enhanced with an extended therapeutic period after application of SIS matrix. The significant differences in pharmacokinetic parameters produced by different formulations demonstrated the influences of SIS copolymer on drug penetrability. Furthermore, the result of skin toxicity test showed that no skin irritation occurred in guinea pig skin after transdermal administration of formulations.
Subject(s)
Adhesives/chemistry , Capsaicin/chemistry , Elastomers/chemistry , Plasticizers/chemistry , Polymers/chemistry , Skin/drug effects , Adhesives/pharmacokinetics , Adhesives/pharmacology , Adhesives/toxicity , Animals , Butadienes/chemistry , Butadienes/pharmacokinetics , Butadienes/pharmacology , Butadienes/toxicity , Capsaicin/pharmacokinetics , Capsaicin/pharmacology , Capsaicin/toxicity , Chemistry, Pharmaceutical/methods , Diffusion , Elastomers/pharmacokinetics , Elastomers/pharmacology , Elastomers/toxicity , Hemiterpenes/chemistry , Hemiterpenes/pharmacokinetics , Hemiterpenes/pharmacology , Hemiterpenes/toxicity , Irritants/chemistry , Irritants/pharmacokinetics , Irritants/pharmacology , Irritants/toxicity , Male , Pentanes/chemistry , Pentanes/pharmacokinetics , Pentanes/pharmacology , Pentanes/toxicity , Permeability , Plasticizers/pharmacokinetics , Plasticizers/pharmacology , Plasticizers/toxicity , Polymers/pharmacokinetics , Polymers/pharmacology , Polymers/toxicity , Rats , Rats, Wistar , Skin/metabolism , Skin Absorption , Styrene/chemistry , Styrene/pharmacokinetics , Styrene/pharmacology , Styrene/toxicityABSTRACT
Formaldehyde mainly emitted from wood adhesives, finishing materials, paint for furniture represents, together with wood dust, a potential carcinogenic risk for wood workers. Aims of this multidisciplinary study are to investigate the possibility of replacing urea-formaldehyde (UF) adhesives in the wood industry with organic and/or inorganic-based glues to obtain a final less toxic product and to evaluate the potential toxicity of wood glued with such new adhesives. For this purpose we selected poplar wood to test an organic new adhesive HBP (Hemp Based Protein), a mixture of hemp flour and cross-linker PAE (polyaminoamide epichlorohydrin), and spruce wood to test an inorganic adhesive geopolymer K-PSS (potassium-polysiloxosialate) plus polyvinyl acetate. For the poplar wood, we also used a commercial panel glued with UF for comparison. We reproduced occupational inhalation exposure during sawing activities of mentioned woods, collected and characterized the wood dusts emitted during sawing and evaluated in vitro their potential cyto-genotoxic and inflammatory effects. We used human lung cells (A549) exposed for 24 h to 20 and 100 µg/mL of collected PM2.5 wood dust. We found that both the new adhesives wood dusts induced a slightly higher apoptotic effect than untreated natural wood dusts particularly in spruce wood. Only geopolymer K-PSS wood dust induced membrane damage at the highest concentration and direct and oxidative DNA damage that could be explained by the different chemical composition and the lower particle sizes in respect to organic HBP adhesive wood dust. We found slight induction of IL-6 release, not influenced by K-PSS treatment, at the highest concentration in spruce wood. For poplar wood, IL-6 and IL-8 induction was found particularly for untreated and UF-treated wood at the highest concentration, where hemp adhesive treatment induced lower inflammation while at lower concentration similar slight cytokine induction was found for all tested wood dusts. This preliminary study shows that natural adhesives used to replace UF adhesives represent an interesting alternative, particularly the organic hemp-based adhesive showing very low toxicity.
Subject(s)
Adhesives/toxicity , Air Pollutants, Occupational/toxicity , Cell Membrane/drug effects , Cytokines/metabolism , DNA Damage/drug effects , Dust/analysis , Wood , A549 Cells , Apoptosis/drug effects , Cell Survival/drug effects , Humans , Inflammation , Inhalation Exposure , Interdisciplinary Research , Models, Theoretical , Occupational Exposure , Particle Size , Toxicity Tests/methodsABSTRACT
Nanocomposites are the dominating class of nanomaterials to come into consumer contact, and were in general assumed to pose low risk. The first data is now emerging on the exposure from nanocomposites, but little is yet known about their hypothetical nanospecific physiological effects, giving ample room for speculation. For the first time, this comprehensive study addresses these aspects in a systematic series of thermoplastic and cementitious nanocomposite materials. Earlier reports that 'chalking', the release of pigments from weathered paints, also occurs for nanocomposites, are confirmed. In contrast, mechanical forces by normal consumer use or do-it-yourself sanding do not disrupt nanofillers (nanoparticles or nanofibers) from the matrix. Detailed evidence is provided for the nature of the degradation products: no free nanofillers are detected up to the detection threshold of 100 ppm. Sanding powders measuring 1 to 80 µm in diameter are identified with the original material, still containing the nanofillers. The potential hazard from aerosols generated by sanding nanocomposites up to the nuisance dust limit is also investigated. In-vivo instillation in rats is used to quantify physiological effects on degradation products from abraded nanocomposites, in comparison to the abraded matrix without nanofiller and to the pure nanofiller. In this pioneering and preliminary evaluation, the hazards cannot be distinguished with or without nanofiller.
Subject(s)
Adhesives/toxicity , Aerosols/toxicity , Manufactured Materials/toxicity , Nanocomposites/chemistry , Nanocomposites/toxicity , Particulate Matter/toxicity , Adhesives/chemistry , Aerosols/chemistry , Animals , Materials Testing/methods , Nanocomposites/ultrastructure , Rats , Rats, Wistar , Risk AssessmentABSTRACT
Ten commercially available denture adhesives, nine soluble formulations (six creams, three powders) and one insoluble product (pad), were analyzed regarding the cytotoxicity profile in direct and indirect assays using L929 fibroblast cells. In the direct assay, fibroblasts were seeded over the surface of a thick adhesive gel (5%, creams; 2.5%, powders and pad). In the indirect assay, cells were cultured in the presence of adhesive extracts prepared in static and dynamic conditions (0.5-2%, creams; 0.25-1%, powders and pad). Cell toxicity was assessed for cell viability/proliferation (MTT assay) and cell morphology (observation of the F-actin cytoskeleton organization by confocal laser scanning microscopy). Direct contact of the L929 fibroblasts with the thick adhesive gels caused no, or only a slight, decrease in cell viability/proliferation. The adhesive extracts (especially those prepared in dynamic conditions) caused significantly higher growth inhibition of fibroblasts and, in addition, caused dose- and time-dependent effects, throughout the 6-72 h exposure time. Also, dose-dependent effects on cell morphology, with evident disruption of the F-actin cytoskeleton organization, were seen in the presence of most adhesives. In conclusion, the adhesives possessed different degrees of cytotoxicity, but similar dose- and time-dependent biological profiles.
Subject(s)
Adhesives/toxicity , Biocompatible Materials/toxicity , Denture Retention , Fibroblasts/drug effects , Actins/drug effects , Animals , Cell Line , Cell Proliferation/drug effects , Cell Shape/drug effects , Cell Survival/drug effects , Coloring Agents , Culture Media , Cytoskeleton/drug effects , Dental Cements/chemistry , Dosage Forms , Dose-Response Relationship, Drug , Fluorescent Dyes , Hydrogen-Ion Concentration , Maleates/chemistry , Materials Testing , Mice , Microscopy, Confocal , Polyethylenes/chemistry , Temperature , Tetrazolium Salts , Thiazoles , Time FactorsABSTRACT
Injectable hydrogels designed for cell therapy need to be adhesive to the surrounding tissues to maximize their retention and the communication between the host and the encapsulated cells. Catechol grafting is an efficient and well-known strategy to improve the adhesive properties of various polymers, including chitosan. However, catechol groups are also known to be cytotoxic as they oxidize into quinones in alkaline environments. Usually, hydrogels made from catechol-grafted chitosan (cat-CH) oxidize quickly, which tends to limit adhesion and prevent cell encapsulation. In this work, we limited oxidation and improved the cytocompatibility of cat-CH hydrogels by grafting chitosan with dihydroxybenzoic acid (DHBA), a small cat-bearing molecule known to have a high resistance to oxidation. We show that DHBA-grafted CH (dhba-CH) oxidized significantly slower and to a lesser extent that cat-CH made with hydrocaffeic acid (hca-CH). By combining dhba-CH with sodium bicarbonate and phosphate buffer, we fabricated thermosensitive injectable hydrogels with higher mechanical properties, quicker gelation and significantly lower oxidation than previously designed cat-CH systems. The resulting gels are highly adhesive on inorganic substrates and support L929 fibroblast encapsulation with high viability (≥90% after 24 hours), something that was not possible in any previously designed cat-CH gel system. These properties make the dhba-CH hydrogels excellent candidates for minimally invasive and targeted cell therapy in applications that require high adhesive strength.
Subject(s)
Adhesives/chemistry , Catechols/chemistry , Cell- and Tissue-Based Therapy/methods , Chitosan/chemistry , Fibroblasts/physiology , Hydrogels/administration & dosage , Adhesives/toxicity , Animals , Biocompatible Materials , Cell Line , Cell Survival/drug effects , Hydrogels/chemistry , Mice , Mucus , Oxidation-ReductionABSTRACT
Hydrogel patches with high toughness, stretchability, and adhesive properties are critical to healthcare applications including wound dressings and wearable devices. Gelatin methacryloyl (GelMA) provides a highly biocompatible and accessible hydrogel platform. However, low tissue adhesion and poor mechanical properties of cross-linked GelMA patches (i.e., brittleness and low stretchability) have been major obstacles to their application for sealing and repair of wounds. Here, we show that adding dopamine (DA) moieties in larger quantities than those of conjugated counterparts to the GelMA prepolymer solution followed by alkaline DA oxidation could result in robust mechanical and adhesive properties in GelMA-based hydrogels. In this way, cross-linked patches with â¼140% stretchability and â¼19â¯000 J/m3 toughness, which correspond to â¼5.7 and â¼3.3× improvement, respectively, compared to that of GelMA controls, were obtained. The DA oxidization in the prepolymer solution was found to play an important role in activating adhesive properties of cross-linked GelMA patches (â¼4.0 and â¼6.9× increase in adhesion force under tensile and shear modes, respectively) due to the presence of reactive oxidized quinone species. We further conducted a parametric study on the factors such as UV light parameters, the photoinitiator type (i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP, versus 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, Irgacure 2959), and alkaline DA oxidation to tune the cross-linking density and thereby hydrogel compliance for better adhesive properties. The superior adhesion performance of the resulting hydrogel along with in vitro cytocompatibility demonstrated its potential for use in skin-attachable substrates.
Subject(s)
Adhesives/chemistry , Gelatin/chemistry , Hydrogels/chemistry , Indoles/chemistry , Methacrylates/chemistry , Polymers/chemistry , Adhesives/chemical synthesis , Adhesives/toxicity , Animals , Cell Survival/drug effects , Cross-Linking Reagents/chemistry , Cross-Linking Reagents/radiation effects , Cross-Linking Reagents/toxicity , Dopamine/chemistry , Dopamine/radiation effects , Gelatin/radiation effects , Gelatin/toxicity , Hydrogels/chemical synthesis , Hydrogels/toxicity , Indoles/chemical synthesis , Indoles/toxicity , Materials Testing , Methacrylates/radiation effects , Methacrylates/toxicity , Mice , NIH 3T3 Cells , Polymerization/radiation effects , Polymers/chemical synthesis , Polymers/toxicity , Skin/metabolism , Swine , Tensile Strength , Ultraviolet RaysABSTRACT
Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.