Assessment of biodegradation and toxicity of alternative plasticizer di(2-ethylhexyl) terephthalate: Impacts on microbial biofilms, metabolism, and reactive oxygen species-mediated stress response.

Although di(2-ethylhexyl) terephthalate (DOTP) is being widely adopted as a non-phthalate plasticizer, existing research primarily focuses on human and rat toxicity. This leaves a significant gap in our understanding of their impact on microbial communities. This study assessed the biodegradation and toxicity of DOTP on microbes, focusing on its impact on biofilms and microbial metabolism using Rhodococcus ruber as a representative bacterial strain. DOTP is commonly found in mass fractions between 0.6 and 20% v/v in various soft plastic products. This study used polyvinyl chloride films (PVC) with varying DOTP concentrations (range 1-10% v/v) as a surface for analysis of biofilm growth. Cell viability and bacterial stress responses were tested using LIVE/DEAD™ BacLight™ Bacterial Viability Kit and by the detection of reactive oxygen species using CellROX™ Green Reagent, respectively. An increase in the volume of dead cells (in the plastisphere biofilm) was observed with increasing DOTP concentrations in experiments using PVC films, indicating the potential negative impact of DOTP on microbial communities. Even at a relatively low concentration of DOTP (1%), signs of stress in the microbes were noticed, while concentrations above 5% compromised their ability to survive. This research provides a new understanding of the environmental impacts of alternative plasticizers, prompting the need for additional research into their wider effects on both the environment and human health.

Phthalate exposure increases interferon-γ during pregnancy: The Atlanta African American Maternal-Child Cohort.

BACKGROUND: The immune system undergoes unique adaptations during pregnancy and is particularly sensitive to environmental chemicals, such as phthalates, which are associated with acute and chronic inflammatory medical conditions. However, current knowledge of how phthalate exposures are associated with systemic inflammation in pregnant people is limited by cross-sectional study designs and single chemical models. Our objective was to estimate the association between repeated measures of prenatal phthalate exposures, examined individually and collectively, and a panel of clinical inflammatory biomarkers. METHODS: In the Atlanta African American Maternal-Child Cohort, biospecimens were collected at mean 11 and 26 weeks gestation (N = 126). Concentrations of eight urinary phthalate metabolites and five serum inflammatory biomarkers, including CRP, IFN-γ, IL-6, IL-10, and TNF-α, were measured. Linear mixed effect regression and quantile g-computation models were used to estimate the associations for single phthalates and their exposure mixture, respectively. RESULTS: Participants who self-reported any use of alcohol, tobacco, or marijuana in the month prior to pregnancy had increased MEP, MBP, MiBP, and CRP, relative to those with no substance use. IFN-γ was elevated in response to MECPP (% change = 17.35, 95 % confidence interval [CI] = 0.32, 32.27), MEHHP (% change = 12.75, 95 % CI = 2.22, 24.36), MEOHP (% change = 11.63, 95 % CI = 1.21, 23.12), and their parent phthalate, ΣDEHP (% change = 15.03, 95 % CI = 0.28, 31.94). The phthalate mixture was also associated with an increase in IFN-γ (% change = 15.03, 95 % CI = 6.18, 24.61). CONCLUSIONS: Our findings suggest DEHP metabolites induce systemic inflammation during pregnancy. The pro-inflammatory cytokine IFN-γ may play an important role in the relationship between prenatal phthalate exposures and adverse pregnancy outcomes.

Ultra-processed and fast food consumption, exposure to phthalates during pregnancy, and socioeconomic disparities in phthalate exposures.

BACKGROUND: Consuming ultra-processed foods may increase exposure to phthalates, a group of endocrine disruptors prevalent in food contact materials. OBJECTIVES: Investigate associations between ultra-processed food intake and urinary phthalates during pregnancy, and evaluate whether ultra-processed foods mediate socioeconomic disparities in phthalate exposures. METHODS: In a socioeconomically diverse sample of 1031 pregnant women from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study in the urban South, the Block Food Frequency Questionnaire was administered and urinary phthalate metabolites were measured in the second trimester. Linear regressions modeled associations between phthalates and overall ultra-processed food consumption, individual ultra-processed foods, and exploratory factor analysis dietary patterns. Causal mediation analyses examined whether ultra-processed food intake mediates relationships between socioeconomic disparities and phthalate exposures. RESULTS: Ultra-processed foods constituted 9.8-59.0 % (mean = 38.6 %) of participants' diets. 10 % higher dietary proportion of ultra-processed foods was associated with 13.1 % (95 %CI: 3.4 %-22.9 %) higher molar sum concentrations of di(2-ethylhexyl) phthalate metabolites (ΣDEHP). 10 % higher consumption of minimally-processed foods was associated with lower ΣDEHP (10.8 %: 3.4 %-22.9 %). Ultra- and minimally-processed food consumption were not associated with non-DEHP metabolites. Standard deviation higher consumptions of hamburger/cheeseburger, French fries, soda, and cake were associated with 10.5 % (4.2 %-17.1 %), 9.2 % (2.6 %-16.2 %), 7.4 % (1.4 %-13.6 %), and 6.0 % (0.0 %-12.4 %), respectively, higher ΣDEHP. Exploratory factor analysis corroborated positive associations of processed food with ΣDEHP, and uncovered a healthy dietary pattern associated with lower urinary ΣDEHP, mono(2-ethyl-5-hydroxyhexyl) (MEHHP), mono(2-ethyl-5-carboxypentyl) (MECPP), mono(2-carboxymethylhexyl) (MCMHP), and mono-isononyl (MINP) phthalates. Significant indirect effects indicated that lower income and education levels were associated with 1.9 % (0.2 %-4.2 %) and 1.4 % (0.1 %-3.3 %) higher ΣDEHP, respectively, mediated via increased ultra-processed food consumption. CONCLUSIONS: Consumption of ultra-processed foods may increase exposure to phthalates. Policies to reduce dietary phthalate exposures from food packaging and processing are needed, as socioeconomic barriers can preclude dietary recommendations as a sole means to reduce phthalate exposures.

Quantitative Measurement of Phthalate Exposure Biomarker Levels in Diaper-Extracted Urine of Japanese Toddlers and Cumulative Risk Assessment: An Adjunct Study of JECS Birth Cohort.

Phthalate exposure monitoring and risk assessment in non-toilet-trained children are rarely reported. This adjunct study of the Japan Environment and Children's Study assessed cumulative health risks in 1.5-year-old toddlers in the Aichi regional subcohort by biomonitoring 16 urinary metabolites of eight phthalate plasticizers. Overnight urine was extracted from toddlers' diapers (n = 1077), and metabolites were quantified using ultraperformance liquid chromatography coupled with tandem mass spectrometry. The analyses' quality was assured by running quality control samples. The highest geometric mean concentration was found for mono-(2-ethyl-5-carboxypentyl) phthalate, followed by mono-isobutyl phthalate (23 and 21 µg/L, respectively). Di-2-ethylhexyl phthalate (DEHP) and di-butyl phthalate exhibited higher risks [hazard quotient (HQ) > 1] than the cutoff level in a small proportion of toddlers; 8 and 14% of toddlers were at cumulative risk of multiple phthalates beyond the cutoff level [hazard index, (HI) > 1], based on the tolerable daily intake of the European Food Safety Authority and the United States Environmental Protection Agency Reference Dose. HI > 1 for antiandrogenicity in creatinine-unadjusted and -adjusted estimations were exhibited by 36 and 23% of the children, respectively. Thus, identifying exposure sources and mitigating exposure are necessary for risk management. Additionally, continuous exposure assessment and evaluation of health outcomes, especially antiandrogenic effects, are warranted.

A new continuous assay for quantitative assessment of enzymatic degradation of poly(ethylene terephthalate) (PET).

Enzymatic degradation of poly(ethylene terephthalate) (PET) has emerged as a promising route for ecofriendly biodegradation of plastic waste. Several discontinuous activity assays have been developed for assessing PET hydrolyzing enzymes, usually involving manual sampling at different time points during the course of the enzymatic reaction. In this work, we present a novel, compartmentalized UV absorbance assay for continuous detection of soluble hydrolysis products released during enzymatic degradation of PET. The methodology is based on removal of the walls separating two diagonally adjacent wells in UV-transparent microplates, to ensure passage of soluble enzymatic hydrolysis products between the two adjacent wells: One well holds an insoluble PET disk of defined dimensions and the other is used for continuous reading of the enzymatic product formation (at 240 nm). The assay was validated by quantifying the rate of mixing of the soluble PET degradation product BHET (bis(2-hydroxyethyl) terephthalate) between the two adjacent wells. The assay validation also involved a simple adjustment for water evaporation during prolonged assays. With this new assay, we determined the kinetic parameters for two PET hydrolases, DuraPETase and LCCICCG, and verified the underlying assumption of steady-state reaction rates. This new continuous assay enables fast exploration and robust kinetic characterization of PET degrading enzymes.

Assessment of health risk and dose-effect of DNA oxidative damage for the thirty chemicals mixture of parabens, triclosan, benzophenones, and phthalate esters.

Humans are constantly exposed to parabens (PBs), triclosan (TCS), benzophenones (BPs), and phthalate esters (PAEs) due to the widespread existence of these chemicals in personal care products (PCPs), and the high frequency of usage for humans. Previous studies indicated each class of the above-mentioned chemicals can exhibit potential adverse effects on humans, in particular DNA oxidative damage. However, the health risk assessment of combined exposures to multiple PCPs is limited, especially the overall dose-effect of mixtures of these chemicals on DNA oxidative damage. In this study, we measured the urinary levels of 6 PBs, TCS, 8 BPs, 15 metabolites of PAEs (mono-PAEs), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from 299 adults simultaneously. PBs, TCS, BPs, and mono-PAEs were frequently detected in urinary samples with median concentrations of 52.888, 0.737, 1.305, and 141.381 ng/ml, suggesting a broad, low-level exposure among participants. Risk assessments indicated approximately 22% and 15% of participants suffered health risks (Hazard index >1) from exposure to TCS and PAEs. The relationship between 8-OHdG levels and chemical exposure was estimated by Bayesian kernel machine regression (BKMR) models. It indicated an overall positive correlation between the mixture of these chemicals and 8-OHdG, with methylparaben and mono-benzyl phthalate contributing the most to this association. Of note, sex-related differences were observed, in which exposure to PCPs led to higher health risks and more pronounced dose-effect on DNA damage in the female population. Our novel findings reveal the health risks of exposure to low-level PCPs mixtures and further point out the overall dose-response relationship between DNA oxidative damage and PCP mixtures.

PAEs Derivatives' Design for Insulation: Integrated In-Silico Methods, Functional Assessment and Environmentally Friendly Molecular Modification.

As a common substance in production and life, phthalic acid esters (PAEs), the main component of plastics, have brought more and more serious problems to the environment. This study normalized the insulation, toxicity, and bioconcentration data of 13 PAEs to eliminate the dimensional coefficients of each index, and then used the comprehensive index method to calculate the comprehensive effect value of PAEs with three properties. The comprehensive effect value was used as the data source to construct the 3D-QSAR model of PAE molecular comprehensive effect. The DAP was selected as the target molecule, the distribution of each force field in the three-dimensional equipotential map was analyzed, and 30 molecular modification schemes were created. The constructed single-effect models of insulation, toxicity, and bioconcentration of PAEs and the scoring function module of DS software were used to evaluate the stability and environmental friendliness of PAE derivative molecules. Four PAE derivatives were screened for increased comprehensive effects, enhanced insulation, and reduced toxicity and bioconcentration. By calculating the binding energy of the target molecule and the derivative molecule with the degrading enzyme under different applied electric fields, it was found that the binding energy of DAP-1-NO2-2-CH2C6H5 decreases more than DAP does when there is an applied electric field, indicating that the degradation ability of degrading enzymes on PAE derivative molecules is reduced, which indirectly proves that the insulation is enhanced. The innovation of this paper lies in the insulation, toxicity, and bioenrichment data of PAEs being processed by mathematical method for the first time, and PAEs with high insulation, low toxicity, and low bioconcentration were designed by building a comprehensive model.

Human risk assessment of di-isobutyl phthalate through the application of a developed physiologically based pharmacokinetic model of di-isobutyl phthalate and its major metabolite mono-isobutyl phthalate.

Di-isobutyl phthalate (DiBP) is a substance used in the production of objects frequently used in human life. Mono-isobutyl phthalate (MiBP), a major in vivo metabolite of DiBP, is a biomarker for DiBP exposure assessment. Therefore, risk assessment studies on DiBP and MiBP, which have not yet been reported in detail, are needed. The aim of this study was to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for DiBP and MiBP in rats and extend this to human risk assessment based on human exposure. Pharmacokinetic studies were performed in male rats following the administration of 5-100 mg/kg DiBP, and these results were used for the development and validation of the PBPK model. In addition, the previous pharmacokinetic results in female rats following DiBP administration and the pharmacokinetic results in both males and females according to multiple exposures to DiBP were used to develop and validate the PBPK model. The metabolism of DiBP to MiBP in the body was very significant and rapid, and the biodistribution of MiBP was broad and major. Furthermore, the amount of MiBP in the body showed a correlation with DiBP exposure, and from this, a PBPK model was developed to evaluate the external exposure of DiBP from the internal exposure of MiBP. The predicted rat plasma, urine, fecal, and tissue concentrations using the developed PBPK model fitted well with the observed values. The established PBPK model for rats was extrapolated to a human PBPK model of DiBP and MiBP based on human physiological parameters and allometric scaling. The reference dose of 0.512 mg/kg/day of DiBP and external doses of 6.14-280.90 µg/kg/day DiBP for human risk assessment were estimated using Korean biomonitoring values. Valuable insight and approaches to assessing human health risks associated with DiBP exposure were provided by this study.

[Cumulative risk assessment of phthalates exposure in preschool children].

Objective: The urine concentrations of phthalate metabolites were used to estimate the cumulative risk assessment in preschool children in Ma'anshan of Anhui province. Methods: Based on the China-Anhui Birth Cohort, the demographic information and urine samples of 3 743 children were collected in Ma'anshan from April 2014 to April 2015. The concentrations of 7 metabolites' [monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl- 5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] of 5 phthalates [dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP)] in the urine samples of the children were measured by solid-phase extration-triple quadrupole high performance liquid chromatography-tandem mass spectrometry-isotope method. In addition, the estimated daily intakes (EDIs) of 5 phthalates were calculated according to the metabolites' concentrations. Cumulative risk assessment was performed using hazard quotient (HQ) and hazard index (HI) methods. Results: The M (Q(R)) of seven metabolite concentrations were 29.58 (18.69-48.26), 26.65 (13.44-56.09), 256.86 (150.99-438.51), 0.12 (0.04-0.32), 6.27 (3.71-11.13), 17.94 (11.94-28.42) and 24.80 (16.05-40.32) µg/g creatinine, respectively. For the EDIs of 5 phthalates, DBP ranked first, followed by DEHP, DMP, DEP and BBzP with the M (Q(R)) of 7.54 (4.41-12.85), 3.35 (2.20-5.42), 0.75 (0.47-1.24), 0.71 (0.36-1.52) and 0.003 (0.001-0.009) µg/(kg·d), respectively. The HQ and HI varied with age, gender and sampling season, the differences were significant (P<0.05). Conclusions: These results indicated that risk of cumulative exposure to phthalates was high in preschool children aged 3-6 years in Ma'anshan. Age, gender and sampling season were influencing factors.

Phthalate exposure and cumulative risk in a Chinese newborn population.

Phthalates have been attracted as a considerable attention in toxicological research as well as public health context due to their ubiquitous occurrence and potential adverse health effects. Newborns are susceptible to the environmental risk factors; however, data are still limited on newborn phthalate exposure and risk assessment worldwide, especially in China. This study was nested in a cross-sectional retrospective study of 1359 pregnant women recruited in Xiamen Maternity and Child Care Hospital, China, during June to July 2012. All urine samples from newborn were collected using disposal diapers during the first two postnatal days, and seven phthalate metabolites were measured by LC-ESI-MS/MS. Phthalate exposure and accumulation risk were evaluated based on the measured newborn urinary internal doses. The detection rate (96.5%) and the median concentration (17.5 ng/mL) of mono-n-butyl phthalate (MBP) were the highest, while monobenzyl phthalate (MBzP) concentration was the lowest with a detection rate (1.50%). By estimating the daily intakes of the parent phthalates, their EDI were 0.04, 0.10, 0.32, 0.00, and 0.12 µg/kg-bw/day for dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalates (DBP), benzyl butyl phthalate (BBzP), and di-(2-ethylhexyl) phthalate (DEHP), respectively. The newborns were commonly exposed to phthalates but no one exceeds the regulated tolerable daily intake (TDI) values in this large newborn population.

Application of catastrophe theory in comprehensive ecological security assessment of plastic greenhouse soil contaminated by phthalate esters.

Large amount of phthalate esters (PAEs) used as plasticizers in polyvinyl chloride (PVC) products has caused ubiquitous contamination to the environment and potential ecology security risk all around the world, especially in places plastic films were indispensably utilized due to the widely proposing of facility agriculture in China. A case of PAEs contamination in four suburb areas of Nanjing was analyzed and discussed in this study. A new frame work has been put forward based on multi-criteria evaluation model and mathematical method of catastrophe theory, using farming work, laboratory determination and relevant environmental standards to measure the ecology security risk of PAEs in study areas. The factors were selected based on the availability of the data and the local conditions. The assessment model involves the contamination status of PAEs in soil and vegetables, the contamination effects of PAEs to human and soil organisms and the contamination source of PAEs from plastic films and other products in the four study facility agriculture areas. An evaluation system of the model was composed of thirteen mesosphere indicators and twenty-five underlying indicators including total PAEs concentration in soils, single PAE concentration in soils, total PAEs concentrations in roots, leafy, solanaceous and stem vegetables, PAE human risks, soil microbial counts, microorganism diversity indices, atmospheric deposition of PAEs, whether sewage wastewater irrigation, planting mode of the facility agriculture areas and climate condition of study areas. The modified evaluation system was used in the assessment of ecology security of the same place based on the data of 2012, and the results suggested that the ecology security indicators were reliable and were agree well with the practical situation of the study areas. The results could provide guidance for the application of health risk assessment of soil environment for the strong objectivity of catastrophe theory compared with other evaluation methods.

The concentrations and cumulative risk assessment of phthalates in general population from Shanghai: The comparison between groups with different ages.

Phthalates are predominantly used as plasticizers in daily consumer products. People are regularly exposed to phthalates through contact with these products. Phthalates are suspected to cause adverse effects in general population. We detected 10 metabolites of 6 phthalates in 3348 urine samples of general population (infants (0-1 yr), children and adolescents (2-19 yr), adults (≥20 yr), and pregnant women) from Shanghai. The Daily intake for phthalates was estimated based on the levels of urinary metabolites. Hazard quotient (HQ) was used to evaluate the risk from the exposure to a single chemical. For the cumulative risk calculation, HQs of different phthalates were added to produce the Hazard index (HI). Overall, exposure was low in adults but presented at a relatively high level throughout childhood. The exposure to some specific phthalates was high in infants and pregnant women. The cumulative risk assessment showed cause for concern mainly for infants and children subgroups. The results indicated that general population from Shanghai was widely exposed to phthalates and the infants were possibly at a high risk of cumulative exposure to phthalates.

Predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men.

BACKGROUND: Certain phthalates are suspected to be endocrine disruptors that are adversely associated with male reproductive health. However, the predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men have not been thoroughly studied. OBJECTIVE: To investigate the predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among adult Chinese males. METHOD: We measured mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-octyl phthalate (MOP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations in seminal plasma and repeated spot-urine samples from 687 men who visited a reproductive center. Mixed-effect models were used to examine the associations of sociodemographic, lifestyle and medical factors with urinary metabolite concentrations. Linear regression models were used to identify predictors of metabolite concentrations in seminal plasma and correlations between metabolite concentrations in spot urine samples and seminal plasma. RESULTS: Measurements taken from spot urine samples poorly predicted same-day seminal plasma concentrations (all R2<0.10). Inverse associations were observed between education level and urinary MBP and MEOHP and between household income and urinary MMP; receiving intravenous infusion therapy was associated with increased urinary MBP, MEHHP and MEOHP, use of facial cleanser/cream was associated with increased MEP, and smoking was associated with increased MEHP. The predictors of metabolite concentrations in seminal plasma differed from those in urine, except for the association of intravenous infusion therapy with MBP. BMI was associated with increased seminal plasma MBP, MEHP and MEOHP, smoking was associated with increased MEP, and contact with plastics was associated with increased MEOHP. CONCLUSIONS: Phthalate metabolite concentrations in adult men varied in accordance with sociodemographic variables, lifestyle factors and intravenous therapy. Measures of metabolite levels in urine may not directly reflect the exposure status of the male reproductive system.

Prevalence and predictors of phthalate exposure in pregnant women in Charleston, SC.

Phthalates are plasticizers commonly detected in human urine due to widespread exposure from PVC plastics, food packaging, and personal care products. Several phthalates are known antiandrogenic endocrine disruptors, which raises concern for prenatal exposure during critical windows of fetal development. While phthalate exposure is ubiquitous, certain demographics are subject to greater or lesser exposure. We sampled urine from 378 pregnant women during the second trimester of gestation living in Charleston, SC, and measured eight urinary phthalate metabolites as biomarkers of phthalate exposure: monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and monomethyl phthalate (MMP). Demographic data was collected from questionnaires administered at the time of specimen collection. All phthalate metabolites were detected in over 93% of urine samples. On average, concentrations were highest for MEP (median = 47.0 ng/mL) and lowest for MMP (median = 1.92 ng/mL). Sociodemographic characteristics associated with elevated phthalate concentrations included being unmarried, less educated, having a low income, high body mass index (BMI), and/or being African American. After racial stratification, age, BMI, education, and income were significantly associated with phthalate concentrations in African American women. Marital status was associated with phthalate concentrations in Caucasian women only, with greater concentrations of MBP, MEHHP, MiBP, and MMP in unmarried versus married women. Results of this cross-sectional study provide evidence for significant racial and demographic variations in phthalate exposure.

Analytical Methodologies for the Assessment of Phthalate Exposure in Humans.

Screening and quantification of phthalate metabolites in biological matrices provide information on the phthalate exposure. The preferred tool for the determination of phthalate metabolites is liquid chromatography-mass spectrometry, typically preceded by a sample extraction step. Method development for the determination of phthalate metabolites by hyphenated techniques faces challenges due to the widespread occurrence of phthalates in the laboratory and sample collection materials that impairs their accurate quantification. Here, the analytical methods that have been developed for the determination of biomarkers of phthalates in various matrices are presented, and limitations and challenges in these applications are discussed.

Cumulative risk assessment of phthalates associated with birth outcomes in pregnant Chinese women: A prospective cohort study.

A prospective cohort study of a Chinese population of mother-neonate pairs (n = 3103) was conducted to investigate the relationship between the cumulative hazard index (HI) of combined diethyl phthalate (DEP), dibutyl phthalate (DBP), dibenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) exposure and birth outcomes. The estimated HI for phthalates was based on phthalate metabolite concentrations in urine collected between 5th and 14th gestational weeks. The median HI values according to the European Food Safety Authority tolerable daily intake (HITDI) and U.S. Environmental Protection Agency reference dose (HIRfD) were 0.358 and 0.187, respectively. A total of 16.3% and 1.9% of the women exhibited HITDI and HIRfD exceeding the value of one, respectively. In unadjusted models, the categories (low < P25, median P25-P50, high > P75) of HITDI were associated with decreased birth weight (ß = -26.34 g, p = 0.021) and head circumference (ß = -0.09 cm, p = 0.029), whereas those for HIRfD were negatively associated with birth weight (ß = -31.74 g, p = 0.005), birth length (ß = -0.11 cm, p = 0.032), head circumference (ß = -0.13 cm, p = 0.003) and chest circumference (ß = -0.10 cm, p = 0.021) in all neonates. Adjustment for potential confounders revealed that HIRfD was inversely associated with head circumference (ß = -0.10 cm, p = 0.020). Stratification by gender indicated that HIRfD was associated with decreased birth length (ß = -0.17 cm, p = 0.041) in infant boys and HITDI was associated with decreased birth weight (ß = -33.12 g, p = 0.036) and head circumference (ß = -0.13 cm, p = 0.027) in girls. This is the first study on the cumulative risk assessment of phthalate exposures in pregnant Chinese women. We found that the HI values of multiple phthalate co-exposure were sex-specifically related to birth outcomes.

Long-term exposure assessment to phthalates: How do nail analyses compare to commonly used measurements in urine.

Phthalate esters (PEs) are easily metabolized and commonly excreted via urine within 24h, therefore their bioaccumulation potential is thought to be rather low. In the present study, we developed a sample preparation combined with a new microextraction method to measure seven PE metabolites in nails. The use of whole nails did not result in significantly different levels compared to powdered nails, which makes the method very fast and user friendly. The method was validated using whole nails showing good accuracy, satisfactory precision and low limits of quantification (2-14ng/g). Although method development was the primary aim of the study, the method was also applied to real samples. PEs were measured in nails of 9 individuals collected at 2 distinct time points (15 days apart) and compared to levels in the respective urine samples (daily morning sample for 15 days). Additionally two volunteers have collected two more urine spots (afternoon and evening) per day. Major metabolites in nails were mono (ethyl hexyl) phthalate (MEHP), monoethyl phthalate (MEP) and sum of mono-n-butyl and mono-isobutyl phthalate (Σ(MnBP, MiBP)) while MEP and Σ(MnBP, MiBP) were the major ones identified in urine. In urine, first void morning urine reflected higher total excretion (sum of PEs of 7.0µg/g creatinine) for all individuals than the afternoon/evening voids. Participants also filled a questionnaire regarding their life-style. The use of hand care products and consumption of pre-packed food was associated with di-(2-ethylhexyl) phthalate (DEHP) oxidative metabolites, while the use of medical devices with butylbenzyl phthalate (BBzP) exposure. Although the metabolism (rate) and other factors that influence the transfer of the analytes from blood or other body compartments into nails needs further investigation, nails can be used to assess exposure to PEs. From our knowledge, urine reflects the excretion of PEs on 'daily basis' while nails show less fluctuation and more stable levels.

Ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME)-a fast new approach to measure phthalate metabolites in nails.

A new, fast, and environmentally friendly method based on ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME) was developed and optimized for assessing the levels of seven phthalate metabolites (including the mono(ethyl hexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5-OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5-oxo-MEHP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monoethyl phthalate (MEP), and mono-benzyl phthalate (MBzP)) in human nails by UPLC-MS/MS. The optimization of the US-DLLME method was performed using a Taguchi combinatorial design (L9 array). Several parameters such as extraction solvent, solvent volume, extraction time, acid, acid concentration, and vortex time were studied. The optimal extraction conditions achieved were 180 µL of trichloroethylene (extraction solvent), 2 mL trifluoroacetic acid in methanol (2 M), 2 h extraction and 3 min vortex time. The optimized method had a good precision (6-17 %). The accuracy ranged from 79 to 108 % and the limit of method quantification (LOQm) was below 14 ng/g for all compounds. The developed US-DLLME method was applied to determine the target metabolites in 10 Belgian individuals. Levels of the analytes measured in nails ranged between <12 and 7982 ng/g. The MEHP, MBP isomers, and MEP were the major metabolites and detected in every sample. Miniaturization (low volumes of organic solvents used), low costs, speed, and simplicity are the main advantages of this US-DLLME based method. Graphical Abstract Extraction and phase separation of the US-DLLME procedure.

Prioritization of in silico models and molecular descriptors for the assessment of ready biodegradability.

Ready biodegradability is a key property for evaluating the long-term effects of chemicals on the environment and human health. As such, it is used as a screening test for the assessment of persistent, bioaccumulative and toxic substances. Regulators encourage the use of non-testing methods, such as in silico models, to save money and time. A dataset of 757 chemicals was collected to assess the performance of four freely available in silico models that predict ready biodegradability. They were applied to develop a new consensus method that prioritizes the use of each individual model according to its performance on chemical subsets driven by the presence or absence of different molecular descriptors. This consensus method was capable of almost eliminating unpredictable chemicals, while the performance of combined models was substantially improved with respect to that of the individual models.

Exposure assessment of phthalates in non-occupational populations in China.

Phthalates have been used worldwide and are ubiquitous in environmental media and human bodies. Based on existing data on phthalate concentrations, distributions of phthalates in the environment and their exposure assessment to non-occupational populations in China can be evaluated. Fifty-three studies, published from January 2000 to October 2010, were reviewed and their data were analyzed in this study. Geographic information system (GIS) was used in mapping the published data of phthalate concentrations and their distributions in environmental media, while scatter diagrams were applied to show the time trends for phthalate concentrations in various environmental media. Results showed that there was a time-dependent increase in ∑phthalates (total phthalates) and DEHP concentrations in air during the past 10 years; phthalate concentrations varied in different areas, among which Guangdong and northeast China were the most polluted. Using Clark's equations, daily intake of ∑phthalates and DEHP in the Pearl River Delta and the Yangtze River Delta was estimated from consumption of contaminated food, water and air. Results showed that daily intake of ∑phthalates and DEHP was 128.63 and 61.29 µg/kg BW/d for adults in the Pearl River Delta, which is significantly higher than those residing in the Yangtze River Delta (33.87 and 24.68 µg/kg BW/d).