Adverse Effect Of Diisononyl Phthalate On Allergic Dermatitis Of Mice Via Long-term Dermal Exposure

The diisononyl phthalate DINP was currently widely, because of the anti-fatigue, anti-migration, anti-extraction properties, used in the fields of plastics, lubricants, resin solvent, building material, adhesive, cosmetic, printing ink as one new kind of plasticizers. DINP is not chemically bound to the products through hydrogen bond and Van der Waals force, and is easily released into the environment in the process of production, use and waste, and humans may be exposed to DINP by the oral, dermal, and inhalation routes. Epidemiological and experimental studies showed that the involvement of phthalate esters (PAEs) to this increase in allergic diseases, and continued exposure to PAEs could increase the incidence and severity of allergic dermatitis by similar immune adjuvant effect. Owing to the environment-friendly property, DINP is used in many personal care products and toys. However, the toxic effects of DINP need to be examined, particularly the effects of long-term dermal DINP exposure. Research into the mechanisms underlying these effects is urgently.In this study, the contact hypersensitivity (CHS) induced by fluorescein isothiocyanate (FITC) in mice is similar to the Allergic dermatitis(AD) of humans in a realistic environment. When the mice with the CHS dermal exposure the derma to DINP in the long term, we found the exacerbation effect of CHS in mice, and discussed the underlying molecular basis of exacerbation effect. Forty-nine male Balb/c mice were subjected to a 40-day dermal exposure to saline or one of three concentrations of DINP and then three rounds of sensitization with vehicle or 0.5% FITC.At the same time, the mice of the saline group and FITC+DINP140+MT group were feed by 30mg/kg MT. On days 41 and 42, the mice were topically sensitized on the shaved abdomens with 0.5% FITC (in 1:1 acetone/DBP)or vehicle (1:1 DBP/acetone) at a volume of 120 μ L. Then the right and left ears of the sensitized mice were respectively smeared by 20 μ L with 0.5%FITC and vehicle.Two ears of the control mice(Saline and MT) were respectively smeared by 20 μ L vehicleWe observed that, after 40 days of dermal exposure, compared with the FITC group, the 14 and 140 mg/kg/day DINP+FITC exposure groups showed aggravated histological changes such as cell infiltration in the ear and physiologic changes such as ear swelling, and increased levels of total IgE, IL-4 and IL-5 in the skin. When the FITC sensitized mice were also exposed to DINP (140 mg/kg), the ROS and MDA content in ear tissues was further upregulated, while the GSH level decreased. MT, with its antioxidant effects, scavenged free radicals induced by FITC and DINP, leading to a comparatively lower level of ROS and MDA, as well as a relative drop in the depletion of GSH.In summary, laboratory results point to a possible correlation between phthalate exposure and allergic disoders such as AD. Experimental studies present support for an exacerbation effect on basic mechanisms in allergic sensitization by several phthalates. Furthermore, the elevation in the oxidative stress levels of the FITC sensitized mice by DINP exposure was reduced with pretreatment of MT. This observation prompted us to draw the conclusion that DINP induced oxidative stress might be responsible for its aggravated effect. This conclusion could help to provide support in therapy of serious atopic disoders such as allergic dermatitis.