diisononyl-phthalate and Asthma

The May 23, 2011, plasticizer incident was one of the most serious food safety issues that ever occurred in Taiwan. Most, if not all, plasticizer-contaminated food items were due to malicious replacement of palm oil with phthalate plasticizer(s) in the cloudy-agent formulas by two upstream manufacturers. The incumbent agencies in Taiwan took necessary actions to minimize the harm caused by the incident and to ease the panic of the general public. In this paper, the incident was briefly reviewed and the situations of phthalate exposure in general public and pregnant women were assessed. Subsequently, the associations between phthalates exposure and the adverse health effects, such as shortened anogenital distance in baby boys, premature thelarche in young girls, endometriosis, adenomyosis, and leiomyoma in women, and decreased semen quality in men, were discussed. Food safety issue has become a worldwide concern and early detection of potential new toxicants in the foods is indispensable. Therefore, it is imperative to establish an international network for early warning or sentinel on food safety.

Topics: Animals; Asthma; Diethylhexyl Phthalate; Environmental Exposure; Food Contamination; Government Regulation; Humans; Phthalic Acids; Plasticizers; Taiwan

Epidemiological evidence indicates a significant relationship between exposure to diisononyl phthalate and allergic asthma. Despite this, the mechanism underlying this association remains unclear. Previous toxicological researches have suggested that the development of allergic asthma may involve the activation of endoplasmic reticulum stress (ERS) and the nuclear factor κ-B (NF-κB) pathways. Nevertheless, it is currently unknown whether these specific signaling pathways are implicated in diisononyl phthalate (DINP)-induced allergic asthma. The objective of this research was to understand how DINP exacerbates allergic asthma in Balb/c mice through ERS and NF-κB pathways. To systematically examine the aggravated effects of DINP in Balb/c mice, we measured airway hyperresponsiveness (AHR), lung tissue pathology, cytokines, and ERS and NF-κB pathway biomarkers. Additionally, we applied the ERS antagonist phenylbutyric acid (4-PBA) or the NF-κB antagonist pyrrolidine dithiocarbamate (PDTC) to verify the mediating effects of ERS and NF-κB on DINP-exacerbated allergic asthma. The results of our experiment show that oral DINP exposure may exacerbate airway hyperresponsiveness and airway remodeling. This deterioration is accompanied by an imbalance in immunoglobulin levels, Th17/Treg cells, ERS, and NF-κB biomarkers, leading to the activation of pro-inflammatory pathways. Furthermore, our study found that the blocking effect of 4-PBA or PDTC can inhibit the Th17/Treg imbalance and effectively alleviate symptoms resembling allergic asthma. In conclusion, ERS and NF-κB signaling pathways play an important role in regulating DINP-induced allergic asthma exacerbations.

Topics: Animals; Asthma; Endoplasmic Reticulum Stress; Mice; Mice, Inbred BALB C; NF-kappa B; Respiratory Hypersensitivity; Signal Transduction

Diisononyl phthalate (DINP) is commonly used as a plasticizer in industrial and consumer product applications. Several studies have suggested a possible link between exposure to DINP and the development of allergic asthma, and the synergistic effect of DINP combined with Ovalbumin (OVA) is a possible way to promote an immune response. These findings are still speculative, since there is insufficient evidence to assess the ability of DINP to influence "allergic asthma pathology". This study was designed to determine any effects of OVA/DINP exposure on airway reactivity, particularly when combined with allergen exposure. Experiments to determine these effects were conducted after 15 days of combined exposure and a subsequent challenge with aerosolized ovalbumin for one week. Airway hyper-responsiveness (lung function), lung tissue pathology, cytokines and oxidative stress biomarkers were investigated. We showed that oral exposure to OVA/DINP could induce airway hyper-responsiveness (AHR), and aggravate airway wall remodeling, and that this deterioration was concomitant with increased immunoglobulin-E and Th2 cytokines secretion. The data also demonstrated that DINP could promote oxidative damage in the lung. In summary, this study showed that DINP has an adjuvant effect on allergic asthma affecting lung function, lung histopathology, immune molecules and causes oxidative damage.

Topics: Adjuvants, Immunologic; Animals; Asthma; Biomarkers; Mice; Ovalbumin; Oxidative Stress; Phthalic Acids; Respiratory Hypersensitivity

What factors and underlying mechanisms influence the occurrence of the atopic march remain unclear. Recent studies suggest that exposure to diisononyl phthalate (DINP) might be associated with the occurrence of atopic dermatitis (AD) and asthma. However, little is known about the role of DINP exposure in the atopic march. In this study, we investigated the effect of DINP exposure on the progression from AD to asthma, and explored the potential mechanisms. We built an atopic march mouse model from AD to asthma, by exposure to DINP and sensitization with OVA. Pyrrolidine dithiocarbamate and SB203580 were used to block NF-κB and p38 MAPK respectively, to explore the possible molecular mechanisms. The data showed that DINP aggravated airway remodeling and airway hyperresponsiveness (AhR) in the progression from AD to asthma, induced a sharp increase in IL-33, IgE, Th2 and Th17 cytokines, and resulted in an increase in the expression of thymic stromal lymphopoietin (TSLP) and in the number of inflammatory cells. Blocking NF-κB inhibited AD-like lesions, and the production of IL-33 and TSLP in the progression of AD, while alleviating airway remodeling, AhR, and the expression of Th2 and Th17 cytokines in both the progression of AD and the asthmatic phenotype. Blocking p38 MAPK in the progression of asthma, inhibited airway remodeling, AhR, and the expression of Th2 and Th17 cytokines. The results demonstrated that exposure to DINP enhanced the immune response to memory CD4

Topics: Airway Remodeling; Animals; Asthma; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Disease Progression; Enzyme Activation; Hypersensitivity, Immediate; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Phthalic Acids; Respiratory Hypersensitivity; Signal Transduction; Specific Pathogen-Free Organisms; Th17 Cells; Th2 Cells; Thymic Stromal Lymphopoietin

Topics: Animals; Asthma; Drug Synergism; Formaldehyde; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Oxidative Stress; Phthalic Acids

Diisononyl phthalate (DINP) and formaldehyde both are associated with asthma and allergies. However, it is unclear about the adverse effect of DINP and formaldehyde exposure on the brain for asthma patients. Here, we determined the effect of DINP and/or formaldehyde exposure on neuroinflammation in brain by a murine asthma model and investigated the underlying mechanisms. Mice were exposed to formaldehyde and/or DINP and sensitization with ovalbumin. The results show that exposure to formaldehyde and/or DINP not only exacerbated allergic asthma-like symptoms, but also promoted neuroinflammation in brain. The incrassation of the airway wall and exacerbation of neuroinflammation were more obviously when mice were subjected to a combined exposure to DINP and formaldehyde. Exposure to DINP and/or formaldehyde enhances oxidative stress and the activation of NF-κB in the prefrontal cortex of mouse asthma model. Exposure to DINP and/or formaldehyde also induced an increase in IL-1β, IL-17, and NGF. Blocking oxidative stress by administering melatonin or inhibiting NF-κB activation by treatment with Dehydroxymethylepoxyquinomicin effectively prevented increasing the levels IL-1β, IL-17 and nerve growth factor. The data indicated that DINP and/or formaldehyde exposure promoted neuroinflammation in the brain through enhanced oxidative stress and activation of NF-κB in a mouse asthma model.

Topics: Animals; Asthma; Disease Models, Animal; Encephalitis; Formaldehyde; Gene Expression Regulation; Interleukin-17; Interleukin-1beta; Male; Mice; Mice, Inbred BALB C; Nerve Growth Factor; NF-kappa B; Ovalbumin; Oxidative Stress; Phthalic Acids; Prefrontal Cortex; Respiratory Hypersensitivity; Signal Transduction

Emerging evidence suggests that prenatal or early-life exposures to environmental contaminants may contribute to an increased risk of asthma and allergies in children. We aimed to the explore associations of prenatal exposures to a large set of environmental chemical contaminants with asthma and eczema in school-age children.. We studied 1024 mother-child pairs from Greenland and Ukraine from the INUENDO birth cohort. Data were collected by means of an interview-based questionnaire when the children were 5-9 years of age. Questions from the ISAAC study were used to define asthma, eczema, and wheeze. We applied principal components analysis (PCA) to sixteen contaminants in maternal serum sampled during pregnancy, including perfluoroalkyl substances (PFASs), metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153, and p,p'-DDE. Scores of five principal components (PCs) explaining 70% of the variance were included in multiple logistic regression models.. In a meta-analysis that included both populations, the PC2 score, reflecting exposure to DiNP, was negatively associated with current eczema (OR 0.71, 95% CI 0.52-0.96). Other associations were not consistent between the two populations. In Ukrainian children, the PC3 score (DEHP) was positively associated with current wheeze (adjusted OR 1.56, 95% CI 1.03-2.37), whereas the PC5 score, dominated by perfluorooctanoic acid (PFOA), was inversely associated with current wheeze (OR 0.64, 0.41-0.99). In Greenlandic children, a negative association of PC4 (organochlorines) with ever eczema (OR 0.78, 0.61-0.99) was found.. We found limited evidence to support a link between prenatal exposure to environmental chemical contaminants and childhood asthma and eczema.

Topics: Asthma; Child; Child, Preschool; Cohort Studies; Dichlorodiphenyl Dichloroethylene; Diethylhexyl Phthalate; Eczema; Environmental Exposure; Environmental Pollutants; Female; Greenland; Humans; Hydrocarbons, Chlorinated; Male; Phthalic Acids; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Principal Component Analysis; Respiratory Sounds; Ukraine