The concentration of phthalates in toys and children's care items in Kosovo.

In this study, one hundred and twenty-eight toys and children's care items available in the Kosovo market were analyzed to determine the presence of phthalates and evaluate if the analyzed samples meet the national and EU standards. Toys and children's care items were imported from twelve countries, most of them from China. Phthalates were extracted and then analyzed using gas chromatography and mass spectrometry. Nine phthalates were analyzed in total, of them, benzyl butyl phthalate, di-isodecyl phthalate, diisobutyl phthalate and di-isononyl phthalate were the most frequently detected phthalates in the analyzed samples. Phthalates were not detected only in three toys and children's care items, others contained one or more phthalates, while none of them contained all (nine) analyzed phthalates. In total, 22 analyzed toys and children's care items did not fulfill at least one of the EU standards, of these 16 were toys and children's care items intended for children under age three and designed to be placed in the mouth. Overall, our work shows that toys and children's care items that exceed EU standards for phthalates are still present in the Kosovo market.

Detecting phthalate esters in sludge particulates from wastewater treatment plants.

This study proposed a method for analysis of 10 phthalate esters compounds from wastewater treatment plant sludges. The analytical efficiency of GC-MS for of target compounds was verified by a standard mixture of phthalate esters. The response factors related to the respective internal standards from a five-point calibration curve quantified the phthalate esters in individual compounds. Based on the literature compiled by environmental agencies, new generation phthalate compounds have been developed, such as di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), as alternative to conventional phthalates. The analytical results showed that the total PAEs concentration was in the range from 7.4 to 138.6 mg kg-1 dw in these seven analyzed sludge samples. More, di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP) and bis(2-ethylhexyl) phthalate (DEHP) contributed to over 99% of PAEs in the sludge. The correlation between total PAEs concentration in household and sewage flow treated at seven WWTPs and concentrations of DEHP, DiNP and DiDP was significant.

Phthalates levels in olive oils and olive pomace oils marketed in Turkey.

Phthalates are used as additives and plasticisers in packaging for personal care and food products. Several investigations reported the harmful impact of phthalates on human health. In this study, different types of olive oils (12 olive oil; 20 extra virgin oil; 4 refined pomace oil) in different packaging materials [polyethylene terephthalate (PET), glass and metal] obtained from local markets in Turkey in 2019, were analysed using GC-MS for the presence of benzyl butyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), and diisodecyl phthalate (DIDP). The average recoveries of the 5 phthalates in olive oils were 87%-100%, with limits of quantification (LOQs) of 0.09-2.28 mg/kg. DEHP was the abundant phthalate in all olive oil samples ranging from below the LOQ (0.23 mg/kg) to 602 mg/kg. In all analysed samples, the levels of DINP and DIDP were less than their LOQ, thus these phthalates were not detected. The highest DEHP content was found in an olive oil sample containing 602 mg/kg, whilst 5 samples did not contain detectable phthalate esters.

Update of the risk assessment of di-butylphthalate (DBP), butyl-benzyl-phthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP), di-isononylphthalate (DINP) and di-isodecylphthalate (DIDP) for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) was asked by the European Commission to update its 2005 risk assessments of di-butylphthalate (DBP), butyl-benzyl-phthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP), di-isononylphthalate (DINP) and di-isodecylphthalate (DIDP), which are authorised for use in plastic food contact material (FCM). Dietary exposure estimates (mean and high (P95)) were obtained by combining literature occurrence data with consumption data from the EFSA Comprehensive Database. The highest exposure was found for DINP, ranging from 0.2 to 4.3 and from 0.4 to 7.0 µg/kg body weight (bw) per day for mean and high consumers, respectively. There was not enough information to draw conclusions on how much migration from plastic FCM contributes to dietary exposure to phthalates. The review of the toxicological data focused mainly on reproductive effects. The CEP Panel derived the same critical effects and individual tolerable daily intakes (TDIs) (mg/kg bw per day) as in 2005 for all the phthalates, i.e. reproductive effects for DBP (0.01), BBP (0.5), DEHP (0.05), and liver effects for DINP and DIDP (0.15 each). Based on a plausible common mechanism (i.e. reduction in fetal testosterone) underlying the reproductive effects of DEHP, DBP and BBP, the Panel considered it appropriate to establish a group-TDI for these phthalates, taking DEHP as index compound as a basis for introducing relative potency factors. The Panel noted that DINP also affected fetal testosterone levels at doses around threefold higher than liver effects and therefore considered it conservative to include it within the group-TDI which was established to be 50 µg/kg bw per day, expressed as DEHP equivalents. The aggregated dietary exposure for DBP, BBP, DEHP and DINP was estimated to be 0.9-7.2 and 1.6-11.7 µg/kg bw per day for mean and high consumers, respectively, thus contributing up to 23% of the group-TDI in the worst-case scenario. For DIDP, not included in the group-TDI, dietary exposure was estimated to be always below 0.1 µg/kg bw per day and therefore far below the TDI of 150 µg/kg bw per day. This assessment covers European consumers of any age, including the most sensitive groups. Based on the limited scope of the mandate and the uncertainties identified, the Panel considered that the current assessment of the five phthalates, individually and collectively, should be on a temporary basis.

Exposure to diisodecyl phthalate exacerbated Th2 and Th17-mediated asthma through aggravating oxidative stress and the activation of p38 MAPK.

Diisodecyl phthalate (DIDP) is considered to be one of the less toxic phthalates. However epidemiological studies suggest that DIDP is associated with the occurrence of asthma. The effect of DIDP exposure on allergic asthma and the underlying mechanism have not been fully elucidated. Here, mice were exposed to DIDP and sensitization with OVA. The results demonstrated that DIDP exposure aggravated allergic asthma. Exposure to 15 mg/kg/day DIDP markedly exacerbated airway remodeling and promoted airway hyperresponsiveness (AhR). The study suggests that exposure to DIDP not only promotes a predominant Th2 response, but also induces Th17-type immunity. The induced allergic asthma was accompanied by elevation of IgE, an increase in TSLP expression and exacerbation of oxidative stress. Inhibition of oxidative stress by Vitamin E effectively alleviated the airway remodeling and AhR induced by DIDP and OVA sensitization. Treatment with Vitamin E inhibited the Th2 response and the production of TSLP. Blocking the activation of p38 MAPK by SB203580 prevented elevation of IL-1ß and IL-17A induced by DIDP and OVA sensitization and effectively alleviated Th17 type asthmatic lesions. These results suggest that exposure to DIDP exacerbates the Th2 and Th17 response through aggravating oxidative stress and activation of the p38 MAPK pathway.

Oral exposure to diisodecyl phthalate aggravates allergic dermatitis by oxidative stress and enhancement of thymic stromal lymphopoietin.

Diisodecyl phthalate (DIDP) is extensively used as an environmentally friendly plasticizer. However, little is known about the adverse effects and the underlying mechanisms of DIDP exposure on immunological diseases. We aimed to determine the role and mechanisms of DIDP exposure in allergic contact dermatitis-like skin lesions. We show that oral DIDP exposure can aggravate allergic dermatitis in mice. Moreover, an increase of ROS, total serum IgE and IL-4 levels were concomitant with this deterioration. We detected the expression of Thymic stromal lymphopoietin (TSLP) and the activation of STATs and NF-κB signal pathways. The data indicated that DIDP in combination with FITC triggers TSLP production. Our results also suggested that DIDP exacerbated the activation of NF-κB signal pathways, with an enhancement in TSLP expression, which potentiated the activation of STATs and the degranulation of mast cells in the skin, and finally exacerbated allergic dermatitis. The study also suggested that melatonin enhanced the expression of Nrf2, up-regulated the antioxidant genes HO-1 and NQO1, reduced the levels of oxidative stress and TSLP, and alleviated allergic dermatitis. The results demonstrated that DIDP exacerbated allergic dermatitis through oxidative stress and enhanced TSLP production.

Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum.

cis-Diamminediiodoplatinum (cis-DIDP) is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4) at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded.

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 µm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 µg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

Adverse effects of diisooctyl phthalate on the male rat reproductive development following prenatal exposure.

In a first study, rats were given diisooctyl phthalate (DIOP, CAS 27554-26-3) at 0, 0.1, 0.5, and 1g/kg/day, by gavage, on gestation days 6-20 (GD). There was a significant increase in resorptions at 1g/kg/day and a reduction in fetal weights at 0.5 and 1g/kg/day. Malpositioned testes were observed in fetuses at 1g/kg/day, and supernumerary lumbar ribs and ossification delay at 0.5 and 1g/kg/day. In a follow-up study, DIOP administered on GD 12-19 reduced fetal testicular testosterone at 0.1g/kg/day and above. Finally, postnatal reproductive assessment was conducted in adult male offspring prenatally exposed to DIOP on GD 12-21. Abnormalities of reproductive system (e.g. hypospadias, non scrotal testes, and hypospermatogenesis) were observed in a few adult males at 0.5g/kg/day, and with a high incidence at 1g/kg/day. Thus, DIOP displayed an antiandrogenic activity and disrupted the male reproductive development.