Dibutyl Phthalate Augments Allergen-induced Lung Function Decline and Alters Human Airway Immunology. A Randomized Crossover Study.

Rationale: Phthalates are a group of chemicals used in common commercial products. Epidemiological studies suggest that phthalate exposure is associated with development or worsening of allergic diseases such as asthma. However, effects of dibutyl phthalate (DBP) or other phthalates found in high concentrations in indoor air have never been examined in allergic individuals in a controlled exposure setting.Objectives: To investigate the airway effects in humans caused by inhalation of a known concentration of a single phthalate, DBP.Methods: In a randomized crossover study, 16 allergen-sensitized participants were exposed to control air or DBP for 3 hours in an environmental chamber followed immediately by an allergen inhalation challenge. Bronchoalveolar wash and lavage were obtained 24 hours after exposure. Lung function, early allergic response, airway responsiveness, inflammation, immune mediators, and immune cell phenotypes were assessed after DBP exposure.Measurements and Main Results: DBP exposure increased the early allergic response (21.4% decline in FEV1 area under the curve, P = 0.03). Airway responsiveness was increased by 48.1% after DBP exposure in participants without baseline hyperresponsiveness (P = 0.01). DBP increased the recruitment of BAL total macrophages by 4.6% (P = 0.07), whereas the M2 macrophage phenotype increased by 46.9% (P = 0.04). Airway immune mediator levels were modestly affected by DBP.Conclusions: DBP exposure augmented allergen-induced lung function decline, particularly in those without baseline hyperresponsiveness, and exhibited immunomodulatory effects in the airways of allergic individuals. This is the first controlled human exposure study providing biological evidence for phthalate-induced effects in the airways.Clinical trial registered with www.clinicaltrials.gov (NCT02688478).

[Studies of di-n-butyl phthalate-OP emulsion in the treatment of demodicidosis].

OBJECTIVE: To observe the curative effect of di-n-butyl phthalate-OP emulsion in the treatment of demodicidosis. METHODS: 447 cases with Demodex infection on face were treated with di-n-butyl phthalate-OP emulsion. Among them, 30 cases suffering from acne, tetter and pustule were also randomly observed. 20 days after treatment negative conversion rate and the therapeutic effect were evaluated. At the same time, the effect of this solution was compared with that of other three medicaments (FuManLing, 2% metronidazole and 8% metronidazole preparations). In vitro test of mites-killing, toxicity test in experimental animals and the safety evaluation for local application were also performed. RESULTS: Results showed that the negative conversion rate was 92.8% (415/447), effective rate for the cases showing evident face damage was 90.0% (27/30). The result also indicated that the OP emulsion medicament was more effective than other three medicaments (P < 0.01). In vitro test showed that this medicament killed all mites within 1 hour. Toxicity test in animals showed that its LD50 was in safe range. It showed no evident stimulation and hypersensitivity by local use. CONCLUSION: Di-n-butyl phthalate-OP emulsion is promising to be developed as a safe, effective therapeutic medicament on demodicidosis.

Purging effect of dibutyl phthalate on leukemia cells involves fas independent activation of caspase-3/CPP32 protease.

We previously found that dibutyl phthalate (DBP) had a pharmacological activity in eliminating tumor cells and could be used as a purging agent in autologous bone marrow transplantation. In this study, we show that DBP can induce apoptosis in MO7e and U937 leukemia cell lines. Treatment of these cells with DBP up-regulates cellular activity of caspase-3/CPP32 and causes apoptosis rapidly as determined by cell viability and dUTP nick end labeling assay. Activation of caspase-3/CPP32 and cleavage of poly(ADP-ribose) polymerase were determined in DBP-induced apoptosis of leukemia cells. However, DBP treatment did not induce the expression of fas. Two caspase inhibitors, z-VAD-fmk and N-acetyl-Asp-Glu-Val-Asp-aldehyde partly blocked the cell death of MO7e cells induced by DBP. These results suggest that fas-independent activation of caspase-3 protease plays important roles in the purging effect of DBP on leukemia cells.

[Effect of dibutyl phthalate on demodicidosis].

OBJECTIVE: To evaluate the curative effect and safety of dibutyl phthalate on demodicidosis. METHODS: A single blinded and controlled study of human demodicidosis treated with dibutyl phthalate was conducted. One hundred and forty three patients with demodicidosis, including 81 acne and 62 rosacea, randomly divided into trial and control groups. The trial group was treated with dibutyl phthalate and control group with "new fumanling" cream twice a day in the early morning and evening respectively for six weeks consecutively. RESULTS: The rates of excellent, good, and fair efficacy and total effective rate in the trial group with acne were 53.7%, 41.5%, 4.9% and 100% respectively, with a significant difference to the control group (P < 0.05). The rates in the trial group with rosacea were 40.6%, 40.6%, 18.8% and 100% respectively, with no statistical difference to the control group (P > 0.05). No complaint of side effects in the trial group was recorded. CONCLUSION: Dibutyl phthalate is highly effective to demodicidosis without prominent adverse reactions.