| Phthalates are widely used as plasticizers which can increase the flexibility, transparency, durability and service life of plastics, and are ubiquitous in our environment. People are exposed to phthalates via inhalation, drinking and diet. Data show that phthalate metabolites are detected in urine, blood, breast milk, fat and sperm. However, exposure data in at-risk groups (e.g. children, elderly people) is quite limited.Di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DINP) are the most commonly used phthalates worldwide. Though their reproductive and developmental toxicity is well known, their immunotoxicity is now gaining more attention in recent studies. The adjuvant effect of DEHP on asthma is confirmed by many animal experiments, but the effect of DINP’s exposure on asthma, especially during the critical window period (e.g. in utero and during lactation exposure), is still unknown.In the current study, we explored environmental exposure of phthalates in China based on literature. A total of61studies published from2000to2012were collected in assessing phthalates exposure in the general Chinese population. Using the geographic information system (GIS), the concentrations and distribution of phthalates in the environment were shown. Daily intake of phthalates in humans in two regions of the Yangtze river and Pearl river delta were calculated. The results showed that there was a time-dependent increase in phthalate concentrations in the environment during the past12years. Phthalate concentrations varied in different areas, among which Guangdong and north China were the most polluted. Daily intake of total phthalates and DEHP was128.6and61.3μg/kg BW/d respectively for adults in the Pearl river delta, which were higher than those residing in the Yangtze river delta (33.9and24.7μg/kg BW/d).In the second part of this study, the internal exposure levels of DEHP metabolites and DINP metabolite in children were investigated. In2012, urine samples were collected from393children (age7～14) in Jiading District of Shanghai. MEHP, MEHHP and MEOHP (DEHP metabolites), and MiNP (DINP metabolite) in urine were determined by high performance liquid chromatography-mass spectrometry. The results showed that the school-age children were generally exposed to MEHP, MEHHP and MEOHP, with median concentrations of1.20,8.79and3.39μg/L, respectively. MiNP was detected in21.6%of urine samples, ranging from lower than the detection limit to13.37μg/L. Younger children might be exposed to higher levels of phthalates.The prevalence of childhood asthma keeps going up. Consistent with this, children’s DINP exposure is also on the rise. We explored the effect of perinatal DINP exposure on asthma attack and its potential mechanism. Wistar rat dams were administrated with DINP daily from gestational day (GD)7to postnatal day (PND)21, with dosages at0(corn oil),5,50and500mg/kg/day, respectively. On PND22,23and37, pups were sensitized with ovalbumin (OVA). On PND44and55, the pups were challenged with OVA aerosol. Then, we assessed airway responsiveness and inflammation of pups, and examined relative cytokine expressions in phosphoinositide3-kinase (PI3K)/Akt pathway in pups’lung tissues. The results showed that maternal DINP exposure at50mg/kg/d promotes OVA-induced asthma response in rat pups, mainly manifested as higher airway inflammation and responsiveness. Enhanced Akt phosphorylation and NF-κB transactivation, and Th2cytokines expression were also observed in pups of50mg/kg/d DINP-treated group. Maternal DINP exposures at5and500mg/kg/d didn’t enhance asthma response in pups. These findings mean that perinatal DINP exposure has an adjuvant effect on asthma attack and that the positive regulation of PI3K/Akt pathway might contribute to the adjuvant mechanism. |
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