Phthalate Metabolite Levels Research Articles

Non-home-prepared meal and fast food intake as exposure sources to non-persistent pollutant among the US population, NHANES 2013-2014

Background: Non-persistent pollutants (NPPs) have been widely used in commercial products, and proven to have adverse health impacts. Despite the various exposure pathways, dietary intake has received more attention due to potential contamination from food processing and packaging. Non-home-prepared meals and fast food are likely more processed and packaged, which may be important exposure pathways for some NPPs. Methods: To assess the associations of urinary NPPs with non-home-prepared meals, and with fast food intake, the data from the National Health and Nutrition Examination Survey (NHANES 2013-2014) were used (N=2,666 for organophosphate ester; N=2,777 for the other chemicals). Dietary information was collected through the questionnaire during household interview and 24-hr dietary recall interview; participants at or below the median were assigned to low exposure group, whereas those above were assigned to high exposure group. Multivariate linear regression accounting for the complex sampling design was applied, and all models were adjusted for sex, age, race/ethnicity, BMI, income, and urinary creatinine. Results: Based on the significance of trend, dose-response relationships were found in some phthalates metabolites, but not for bisphenols, parabens or organophosphate esters with non-home-prepared meals, and with fast food intake. The participants with low and high frequency of non-home-prepared meals have 15.3% (CI 3.7-28.1%) and 66.8% (CI 39.9-98.8%) increase in urinary Σdiisononyl phthalate metabolites (ΣDiNPm) levels compared to non-exposed group. Those with low and high fast food intake with in the past 24 hours have 31.1% (CI 9.8-56.4%) and 70.4% (CI 51.2-92.0%) increase in urinary ΣDiNPm levels compared to no intake group. Similar findings were also found for urinary Σdi(2-ethylhexyl)phthalate metabolites (ΣDEHPm), mono(carboxyisononyl) phthalate (MCiNP), and mono-(3-carboxypropyl) phthalate (MCPP). Conclusion: Human phthalate exposure may be attributed to non-home-prepared and fast food consumption, whereas paraben, bisphenol, and organophosphate ester exposures may have different exposure pathways among the US population.

Phthalates exposure, thyroid function and glucose metabolism: exploring associations and mediation effects in Taiwanese adults

Background: Information regarding the mediation effects of thyroid function in associations between phthalates exposure and glucose metabolism including insulin resistance is unclear. Objective: Our aim was to examine whether thyroid hormone levels could mediate the associations between phthalates exposure and insulin resistance. Method: Eleven urinary phthalate metabolites levels, five thyroid hormone levels and insulin resistance (by using the Homeostatic Model Assessment of estimated Insulin Resistance [HOMA-IR]) were determined in a cross-sectional study comprised of 217 Taiwanese adults. Associations between urinary phthalate metabolite levels, serum thyroid hormone levels and HOMA-IR were explored using multiple regression models. Mediation analysis was conducted to assess the role of thyroid function in the associations between phthalates exposure and HOMA-IR. Results: Urinary mono-ethylhexyl phthalate (MEHP) levels were negatively associated with free thyroxine (free T4) (β= -0.018 ; 95% confidence interval [CI]: -0.031, -0.005 ) and positively associated with HOMA-IR (β=0.051, 95% CI: 0.012, 0.090), respectively. Urinary mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) levels were associated with free T4 (β= -0.036, 95% CI:-0.056, -0.017) and HOMA-IR (β=0.070 , 95% CI: 0.013, 0.126), respectively. Free T4 was negatively associated with HOMA-IR (β= -0.757, 95% CI:-1.122, -0.392). The results of mediation analysis indicated that 24% of the association between urinary MEHP and HOMA-IR was mediated by free T4, as well as 35% of the association between urinary MEOHP and HOMA-IR was mediated by free T4. Conclusions: Our findings support the hypothesis that thyroid function could mediate the association between phthalates exposure and glucose metabolism in adults.

Phthalate Exposure and Developmental Delay in Children

Background: The role of phthalate exposure at different stages in the nervous system is not well-known. This study aims to evaluate the effects of phthalate exposures on immunoglobulin E (IgE) levels and developmentaldelay in children by objective biomarkers. Methods: A total of 453 children from Childhood Environment and Allergic Diseases Study cohort with urine samples were recruited in Taiwan. Urine phthalate metabolites (MEP, MBP, MBzP, and 5OH-MEHP) were measured by UPLC-MS/MS at age 3. At age 6, information on the development of developmental delay and serum total IgE were collected. The association between urine phthalate metabolites levels at different stages and serum IgE and developmental delay were evaluated by multivariate linear regression and logistic regression. Results: Urine phthalate metabolites levels were higher at age 3 than those at age 6. 5OH-MEHP levels at age 3 positively correlated with serum IgE levels (per ln-unit: β=0.191, p=0.02). When dividing into quartiles, urine 5OH-MEHP levels at age 3 were associated with the developmental delay at age 6 (adjusted OR=3.65, 95%CI (1.11-11.98)). MEP, MBP, and MBzP levels were also positively associated with the developmental delay, though failed to reach statistically significance. Interestingly, analyses stratified by gender revealed that 5OH-MEHP levels were significantly associated with developmental delay, particularly in boys with OR (95%CI) of 4.40(1.10-17.58). Conclusion: Early life phthalate exposure may increase the risk of developmental delay, particularly in boys.

The internal exposure of phthalate metabolites and bisphenols in waste incineration plant workers and the associated health risks

Many hazardous substances can be released during incineration of municipal solid waste (MSW), which pose a potential threat to human health. As additives, phthalates (PAEs) and bisphenols (BPs), which are widely used in daily goods, are likely to be present in the released hazardous substances. In the present study, we investigated the urinary levels of phthalate metabolites (mPAEs) and BPs in workers in an MSW incineration plant (the exposed group) and in residents 8 km away (the control group) in Shenzhen, China. The results showed that the median total urinary concentration of mPAEs in workers was significantly higher than that in residents (1.02 × 103 vs. 375 ng/mL). However, there was no significant difference between workers and residents for BPs. Among the mPAEs measured, the most abundant compound was mono-n-butyl phthalate in both exposed and control groups. Monoethyl phthalate and monomethyl phthalate might be potential markers for MSW incineration because of significantly high levels in the exposed group. The workers engaged in different types of workshops showed no significant differences in the urinary levels of mPAEs, also for BPs. It was worth noting that 70.8% of workers were at risk of the non-carcinogenic effects caused by PAEs with diethylhexyl phthalate having the highest risk. Actions should be taken to reduce the risks caused by these hazardous chemicals.

Levels of endocrine-disrupting chemicals are associated with changes in the peri-pubertal epigenome.

Puberty marks a transition period, which leads to the attainment of adult sexual maturity. Timing of puberty is a strongly heritable trait. However, large genetic association studies can only explain a fraction of the observed variability and striking secular trends suggest that lifestyle and/or environmental factors are important. Using liquid-chromatography tandem-mass-spectrometry, we measured endocrine-disrupting chemicals (EDCs; triclosan, bisphenol A, benzophenone-3, 2,4-dichlorophenol, 11 metabolites from 5 phthalates) in longitudinal urine samples obtained biannually from peri-pubertal children included in the COPENHAGEN puberty cohort. EDC levels were associated with blood DNA methylation profiles from 31 boys and 20 girls measured both pre- and post-pubertally. We found little evidence of single methylation sites that on their own showed association with urinary excretion levels of EDCs obtained either the same-day or measured as the yearly mean of dichotomized EDC levels. In contrast, methylation of several promoter regions was found to be associated with two or more EDCs, overlap with known gene–chemical interactions, and form a core network with genes known to be important for puberty. Furthermore, children with the highest yearly mean of dichotomized urinary phthalate metabolite levels were associated with higher promoter methylation of the thyroid hormone receptor interactor 6 gene (TRIP6), which again was mirrored by lower circulating TRIP6 protein levels. In general, the mean TRIP6 promoter methylation was mirrored by circulating TRIP6 protein levels. Our results provide a potential molecular mode of action of how exposure to environmental chemicals may modify pubertal development.

Urinary bisphenol A, phthalate metabolites, and obesity: do gender and menopausal status matter?

Previous studies of urinary bisphenol A (BPA), phthalate metabolites, and obesity risk have shown inconsistent results. Menopausal status is one of the main factors that affect hormone secretion change in women. In this study, we examined whether urinary BPA and phthalate metabolite levels are associated with obesity and whether the associations differ by sex and menopausal status in a sample of Korean adult populations. We recruited participants at three branches (Yeouido, Gangnam, and Gwanghwamun) of the Korea Medical Institute, a nationwide health check-up center, from 2015 to 2016. Urinary BPA level was measured by high-performance liquid chromatography-tandem mass spectrometry (Agilent 6490 Triple Quad LC-MS/MS; Agilent Technologies, CA, USA). Urinary six phthalate metabolites were analyzed with ultra-high-performance liquid chromatography-tandem mass spectrometry (TSQ Quantum Access Mass; Thermo Fisher Scientific, MA, USA). Participants with body mass index ≥ 25 kg/m2 were defined as general obesity group. Men with waist circumference (WC) ≥ 90 cm and women with WC ≥ 85 cm were defined as abdominal obesity group. Age, sex, alcohol intake, smoking, and exercise were considered in multivariate logistic regression models. Among the total of 702 participants, 211 participants were classified into the general obesity group, and 131 participants were classified into the abdominal obesity group. Urinary phthalate metabolite levels were not associated with general and abdominal obesity in men and women. However, in women, urinary BPA concentration was positively associated with abdominal obesity (OR = 1.50, 95% CI 1.00-2.26). Also, the association was stronger in postmenopausal women (OR = 2.23, 1.01-4.92), while it was weak in premenopausal women (OR = 1.31, 0.78-2.20). In this study, urinary BPA concentration was associated with abdominal obesity in women, especially postmenopausal women. Future studies should consider sex and menopausal status when investigating associations between urinary BPA, phthalate metabolites levels, and obesity.

844 Increased urine phthalate metabolite levels associated with eczema diagnosis

844 Increased urine phthalate metabolite levels associated with eczema diagnosis

Trophic Transfer of Micropollutants and Their Metabolites in an Urban Riverine Food Web.

Trophic magnification factors (TMFs, i.e., the average change in the log-concentration of a pollutant per trophic level) have been extensively assessed for the so-called persistent organic pollutants, especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), which are biomagnified along the food web. In contrast, trophic dilution was documented for pollutants with a high metabolic conversion rate, such as phthalate plasticizers and polycyclic aromatic hydrocarbons (PAHs). However, the fate of their metabolites across the food web has been rarely investigated. In this comparative study, the trophodynamics of 104 micropollutants and 25 of their metabolites were investigated in a freshwater food web from the urban Orge River, France. Trophic levels were determined using stable isotopes. Pyrethroid pesticides and their metabolites were not detected. As predicted, PCBs and OCPs biomagnified (TMF >1), while all chlorinated paraffins (CPs), PAHs, and phthalates underwent a trophic dilution (TMF <1). TMFs significantly decreased with a metabolic transformation rate and increased with hydrophobicity. The levels of PAH or phthalate metabolites were not significantly correlated with trophic levels or underwent a trophic dilution. This study highlighted that the relative contribution of metabolite levels in TMF values calculated for both parent compound and its metabolite(s) is weak compared to TMF values of the parent compound only in a riverine food web.

Prenatal and early childhood phthalate exposures and thyroid function among school-age children

BackgroundLimited studies have investigated the association between prenatal and early childhood phthalate exposures and thyroid function among children. ObjectivesTo investigate the association between early life phthalate exposure and thyroid function among school-age children, considering both prenatal and early childhood exposures, using longitudinal data from an established prospective cohort. MethodsWe measured urinary phthalate metabolite levels during pregnancy and at 2, 4, and 6 years of age and conducted thyroid function tests at 6 years of age. We assessed the associations between phthalate metabolite levels and thyroid function using linear regression and Bayesian kernel machine regression (BKMR) models (n = 492). ResultsIn linear regression models, a doubling of urinary mono-n-butyl phthalate (MnBP) levels, measured during pregnancy and at 4 years of age, was associated with lower thyroid-stimulating hormone (TSH) levels at 6 years of age (−5.0%, 95% confidence interval [CI]: −8.8%, −1.0% and −5.7%, 95% CI: −9.7%, −1.5%, respectively). A similar association was found between mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) levels at 4 years of age and TSH levels at 6 years of age (−5.5%, 95% CI: −9.7%, −1.1%). Urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (2.3%, 95% CI: 0.1%, 4.5%) and MEOHP levels at 2 years of age (2.2%, 95% CI: 0.1%, 4.4%) and mono-2-ethyl-5-carboxypentyl phthalate (1.4%, 95% CI: 0.1%, 2.7%) and mono-benzyl phthalate levels at 6 years of age (1.1%, 95% CI: 0.4%, 1.9%) were associated with higher triiodothyronine (T3) levels at 6 years of age. Urinary MnBP during pregnancy, MEHHP, MEOHP, and MnBP at 4 years of age were also associated with lower free thyroxine (fT4) × TSH. In BKMR models, urinary MnBP levels during pregnancy were associated with lower TSH levels and fT4 × TSH (both posterior inclusion probabilities: 0.99). ConclusionsOur findings suggest that early life phthalate exposure influences subsequent thyroid function. However, the results should be interpreted cautiously, because a single spot urine sample was used to quantify the phthalate exposures at each time point.

Risk assessment of exposure to phthalates in breastfeeding women using human biomonitoring

In this study, we assessed the presence of 14 phthalate metabolites in the urine of 104 lactating mothers from Valencia (Spain) who took part in the human biomonitoring project BETTERMILK. Nine of the metabolites studied showed detection frequencies >80%, whereas the rest of the metabolites presented low detection frequencies (<5%). The concentrations ranged from <LoQ to 1291 ng/mL with monoethyl phthalate showing the highest concentration, with a geometric mean of 34.90 ng/mL. In general, the phthalate metabolite levels quantified in the present study were lower than the urinary levels found in previous studies that involved lactating mothers. The consumption of packaged juices and the frequency of deodorant usage were predictors of some phthalate metabolite levels in urine. In order to put the biomonitoring data in a risk assessment context, guide values for the different phthalates were used and the respective hazard quotients were calculated, which ranged from 0.0036 (benzylbutyl phthalate) to 0.49 (di-2-ethylhexyl phthalate) at the 95th percentile level. Consequently, no risk was appreciated in the studied population.

Characterization of phthalate exposure in relation to serum thyroid and growth hormones, and estimated daily intake levels in children exposed to phthalate-tainted products: A longitudinal cohort study

BackgroundNo information is available on the long-term effects on thyroid and growth hormones of children exposed to phthalate-tainted products, despite the infamous 2011 Taiwan phthalate episode. We investigated estimated daily intake levels and their long-term effects on serum thyroid and growth hormone levels in children. MethodsWe recruited 166 children (2–18 years old) in three visits who provided specimens and filled out a questionnaire from the Risk Assessment of Phthalate Incident in Taiwan (RAPIT) project study from 2012 to 2016. Morning spot urine samples were analyzed for nine phthalate metabolites. Serum thyroid (triiodothyronine [T3], thyroxine [T4], and free T4) and growth hormone (insulin-like growth factor-1 [IGF-1] and its binding protein 3 [IGF-BP3]) levels were measured. A generalized estimating equation model was used to evaluate associations between phthalate metabolite levels and children’s thyroid and growth hormone levels. ResultsThe median metabolite levels of monomethyl phthalate (MMP), Σdibutyl phthalate (DBP), and Σdi-(2-ethylhexyl) phthalate (DEHP) at visits 1, 2, and 3 were 6.59, 10.5, and 21.0 ng/mL, 0.15, 0.24, and 0.20 nmol/mL, and 0.15, 0.17, and 0.12 nmol/mL, respectively. After adjusting for potential confounding factors, we found that levels of urinary MMP were negatively associated with T3 (β = −0.013, p = 0.047), T4 (β = −0.016, p = 0.006), free T4 (β = −0.012, p = 0.002), and IGF-BP3 (β = −0.025, p = 0.003). Urinary mono-ethyl phthalate (MEP) was negatively associated with IGF-1 (β = −0.027, p = 0.029) and IGF-BP3 (β = −0.016, p = 0.018). In addition, serum free T4 was positively associated with urinary mono-2-ethyl-5-hydroxy hexyl phthalate (MEHHP) (β = 0.016, p = 0.043), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 0.015, p = 0.024), and ΣDEHPm (β = 0.019, p = 0.020). ConclusionsOur findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products.

Longitudinal effect of phthalates exposure on allergic diseases in children

BackgroundEnvironmental chemicals, such as phthalates, phenols, and parabens, may affect children's immune development and contribute to the risk of atopic diseases and asthma. ObjectiveTo evaluate the associations between prenatal and childhood phthalate exposure and atopic diseases in children at the age of 9 years. MethodsThis analysis is restricted to 145 mother-child pairs from the prospective Polish Mother and Child Cohort Study. Phthalate metabolite levels were assessed in the urine samples collected from mothers during the third trimester of pregnancy and from children at age of 2 and 9 years. For the appropriate recognition of children's health status, a questionnaire was administered to the mothers and completed with information from the medical record of each child. The clinical examination was performed by a pediatrician/allergist in the presence of the mother or a relative. ResultsA higher urine concentration of mono-2-ethyl-5-oxohexyl phthalate increased the risk of food allergy in children at the age of 9 years (odds ratio [OR], 1.75; 95% CI, 1.19-2.57; P = .004) and decreased the risk of atopic dermatitis (OR, 0.49; 95% CI, 0.27-0.87; P = .02). For mono-2-ethyl-5-hydroxyhexyl phthalate, an increased risk of atopic dermatitis was observed (OR, 1.90; 95% CI, 1.18-3.05; P = .008). A higher urine concentration of mono-benzyl phthalate increased the risk of asthma in children (OR, 1.67; 95% CI, 1.08-2.58; P = .02), but the risk of asthma decreased when the concentration of mono-2-ethylhexyl phthalate was higher (OR, 0.64; 95% CI, 10.43-0.97; P = .04). ConclusionOur study has not provided clear evidence of the negative effect of phthalate exposure during pregnancy and within the 9 years after birth on allergic diseases in children.

Exposure to Mono-n-Butyl Phthalate in Women with Endometriosis and Its Association with the Biological Effects on Human Granulosa Cells.

To study the association between urinary phthalate metabolite levels, endometriosis, and their effects on human granulosa cells, we recruited patients who underwent laparoscopy to confirm endometriosis (n = 123) and control patients (n = 78). Liquid chromatography–tandem mass spectrometry was used to measure the following five urinary phthalate metabolites: mono-n-butyl phthalate (MnBP), mono(2-ethylhexyl) phthalate, monobenzyl phthalate, mono(2-ethyl-5-oxo-hexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate. Urinary MnBP levels were higher in patients with endometriosis than in controls after multivariable logistic regression including the number of deliveries, body mass index, and use of medicine as covariables. MnBP correlates with other phthalate metabolites. Previous studies found that endometriosis was a detrimental condition for granulosa cells. In our study, we observed whether MnBP affected granulosa cells. MnBP treatment altered the gene expression of BIRC5, BUB1B, CDC20, cyclin B1, IL-1β, TNF-α, inhibin-B, StAR, and P450ssc and attenuated the ratio of the mitochondrial membrane potential in human granulosa cells. Moreover, MnBP decreased the expression of the anti-Mullerian hormone. These findings suggest that MnBP concentration is associated with endometriosis and may affect the health and steroidogenesis of human granulosa cells.

Assessment of the possible association between phthalate exposure and attention deficit hyperactivity disorder in egyptian children

Abstract Background Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood. Phthalates are industrial chemicals often used in personal care products and to soften plastics in toys and household items such as food containers, and medical devices. Animal studies have reported that the phthalate compound might cause hyperactivity and impulsivity in rats. However, the relation between phthalates and ADHD in human is still controversial. Objective The aim of our study is to investigate the possible association between urinary phthalate metabolite levels and attention deficit disorder, learning disability in 6–12-years old children. Methods Urine samples were obtained from 80 children. All children were selected from the attendants of Abu elreesh child psychiatry outpatient clinic, Cairo University. subjects were divided into two main groups Group A consisted of 50 children with Attention-deficit/hyperactivity disorder (ADHD) diagnosed by psychiatric consultant and Group B consisted of 30 normal children. In urine, mono butyl phthalate (MBP) metabolite were measured with high performance liquid chromatography (HPLC). Results The mean concentration of MBP level was (15.539±8.316) for cases (group A) and (8.085 ±2.426) for controls (group B) with significant difference between groups. Also there was significant correlation with processing milk, plastic containers, toys, cosmetics, wall, and floor material containing phthalate exposure and higher level of (MBP) in urine of group A. Conclusion The present study showed association between phthalate metabolites in urine and symptoms of ADHD among school-age children.

What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.

SummaryBackgroundEpidemiological studies indicate that gene–environment interactions play a role in atopic dermatitis (AD).ObjectivesTo review the evidence for gene–environment interactions in AD aetiology, focusing on filaggrin (FLG) loss‐of‐function mutations.MethodsA systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS‐I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta‐analysis.ResultsOf 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG–environment interactions in six of the studies (P‐value for interaction ≤ 0·05), including early‐life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss‐of‐function mutations and exposure to specific environmental factors, and variation in exposure definitions.ConclusionsEvidence on FLG–environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411.

Use of stored serum in the study of time trends and geographical differences in exposure of pregnant women to phthalates

BackgroundExposure to some phthalate diesters has been associated with adverse reproductive health outcomes in both rodents and humans indicative of anti-androgenic effects. Exposure during sensitive periods of development, such as prenatally, is of particular concern. ObjectivesWe wished to investigate whether phthalate metabolites measured in maternal serum samples from historical birth cohorts can be used to assess prenatal exposure. Further, we aimed to study temporal and geographical trends in phthalate exposure across three different birth cohorts. MethodsWe compared phthalate metabolite levels in maternal serum samples from an Australian (1989–91) and a Danish (1997–2001) birth cohort with levels in serum and urine samples from a recent Danish birth cohort (2012–14). Samples were analysed for 32 phthalate metabolites from 15 phthalate diesters by isotope-diluted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Correlations between metabolites were tested by Spearman rank correlation test, and differences between the cohorts were tested by Mann-Whitney U test. ResultsOverall, we observed large variations in serum phthalate metabolite levels between individuals. Secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) in serum were weakly to moderately and positively correlated to the levels measured in urine, and secondary metabolites of DEHP were also moderately to strongly and significantly correlated in serum. Correlations with mono-(2-ethyl-hexyl) phthalate (MEHP) and mono-iso-nonyl phthalate (MiNP), the two primary metabolites of DEHP and DiNP, were inconsistent, and we found indications of sample contamination. We observed some significant differences in phthalate metabolite levels between the three cohorts with generally higher levels in the older birth cohorts. ConclusionBased on comparison across two older birth cohorts and a recent cohort, our results support the concept that historical biobanked serum samples may be used for assessment of prenatal exposure to phthalates when using serum levels of the monoesters of the low-molecular weight (LMW) phthalates and the secondary metabolites of the high-molecular weight (HMW) phthalates. Serum phthalate measurements are, however, not suitable for human biomonitoring and should only be used to exploit historical samples from cohorts, where urine samples were not collected. Our findings suggest that phthalate exposure may have decreased over time from the early 1990s to the 2010s.

Associations of lifestyle factors with phthalate metabolites, bisphenol A, parabens, and triclosan concentrations in breast milk of Korean mothers

The toxicity of endocrine disruptors depends on the synergistic interactions of biological, environmental, and behavioral factors. The specific effects of diet, consumer product use, and behaviors, however, are debated in the literature, particularly with regard to endocrine disruptors found in breast milk. This study aimed to measure the levels of phthalate metabolites, bisphenol A, parabens, and triclosan in breast milk and to investigate their associations with various lifestyle factors. The breast milk samples as well as surveys were collected from 221 first-time mothers throughout South Korea and each sample was analyzed for the presence of 15 endocrine disruptors. Phthalate metabolites were detected in 5.4–83.3% of the samples, with median concentrations of 0.08–1.72 μg/L, while bisphenol A, parabens, and triclosan were detected in 25.8–88.2% of the samples, with median concentrations of 0.12–1.47 μg/L. High levels of endocrine disruptors were associated with frequent consumption of fish and cup noodles; the use of plastic and disposable food containers; the use of air fresheners, lotions and make-up; the purchase of new furniture; and socioeconomic status. We also observed the potential role of moderate walking activity on the reduction of these chemicals in breast milk. Our data provide evidence of the potential effects of diet, consumer products, and behavior on the presence of phthalate metabolites, bisphenol A, parabens, and triclosan in breast milk. Future studies should include community or regional impact on a mothers’ exposure to endocrine disruptors, to assess the joint contribution of both individual and neighborhood factors.

Time course of phthalate cumulative risks to male developmental health over a 27-year period: Biomonitoring samples of the German Environmental Specimen Bank

In several human biomonitoring surveys, changes in the usage patterns of phthalates have come to light, but their influence on the risks associated with combined exposures is insufficiently understood. Based on the largest study to date, the 27-year survey of urinary phthalate metabolite levels in 24-hour urine samples from the German Environmental Specimen Bank, we present a deep analysis of changing phthalate exposures on mixture risks. This analysis adopts the Hazard Index (HI) approach based on the five phthalates DBP, DIBP, BBP, DEHP and DINP. Calculations of the hazard index for each study participant included updated phthalate reference doses for anti-androgenicity (RfDAAs) that take account of new evidence of phthalates’ developmental toxicity.The Maximum Cumulative Ratio (MCR) approach was used to establish whether a subject’s combined exposure was dominated by one phthalate or was influenced by several phthalates simultaneously. Generally, over the years there was a shift towards lower HIs and higher MCRs, reflecting an increased complexity of the combined exposures. The decade from 1988 to about 1999 was characterised by rather high HIs of between 3 and 7 (95th percentile) which were driven by exposure to DBP and DEHP, often exceeding their single acceptable exposures. Traditional single phthalate risk assessments would have underestimated these risks by up to 50%. From 2006 onwards, no study participant experienced exposures above acceptable levels for a single phthalate, but combined exposures were still in excess of HI = 1. From 2011 onwards most individuals stayed below HI = 1. In interpreting these results, we caution against the use of HI = 1 as an acceptable limit and develop proposals for improved and more realistic mixture risk assessments that take account of co-exposures to other anti-androgenic substances also capable of disrupting the male reproductive system. From this perspective, we regard HIs between 0.1 and 0.2 as more appropriate for evaluating combined phthalate exposures. Assessed against lowered HIs of 0.1 – 0.2, the combined phthalate exposures of most study participants exceeded acceptable levels in all study years, including 2015. Continued monitoring efforts for phthalate combinations are required to provide the basis for appropriate risk management measures.

Investigation of phthalate metabolites in urine and daily phthalate intakes among three age groups in Beijing, China

Phthalates are widely used as binders and plasticizers in industrial and consumer products but show diverse toxicity. We investigated the level of human exposure to phthalates in Beijing, one of the most densely populated cities in the world. In this study, 12 metabolites of phthalates were measured in 70 spot urine samples collected from Beijing residents from August 2017 to April 2018 using ultra high-performance liquid chromatography tandem mass spectrometry. We found that metabolites of phthalates were ubiquitous in all urine samples. Total concentrations of phthalate metabolites ranged from 39.6 to 1931 ng mL−1, with median concentrations were in decreasing order of children (371 ng mL−1)> younger adults (332 ng mL−1)> older adults (276 ng mL−1). Mono-n-butyl phthalate (MnBP) was the predominant compound, and occurred at concentrations greater than those reported for people in other countries. The mean values of estimated daily intakes (EDIs) of ∑phthalate were 35.2, 10.3 and 10.9 ng (kg-bm)−1 d−1 for children, younger adults and older adults, respectively. EDIs of di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and di-(2-ethylhexyl) phthalate (DEHP) exceeded reference values suggested by the US Environmental Protection Agency and the European Food Safety Authority. When concentrations were normalized to volume or creatinine-adjusted, hazard quotients (HQs) for 40 of 70 participants exhibited larger HQs >1 for individual phthalates, which was indicative of potential for adverse effects. Thus, exposure to phthalates might be a critical factor contributing to adverse health effects in Beijing residents. To the best of our knowledge, this is the first study to establish a pre-baseline level of urinary phthalate metabolites among residents in Beijing.

Biomonitoring of bisphenols A and S and phthalate metabolites in hair from pregnant women in Crete

Phthalates, bisphenols A and S (BPA, BPS) are used as plasticizers and many of them are documented or suspected of being endocrine disruptors. Several studies indicate that exposure during pregnancy may affect the newborn's health and development. The aim of this cross-sectional study is the biomonitoring of seven phthalate metabolites, BPA and BPS in hair from 100 pregnant women in Crete. The most frequently detected compounds were monoethylhexyl phthalate (mEHP) (68%), mono isobutyl phthalate (miBP) (40%), BPA (37%), BPS (34%) and mono-n-butyl phthalate (mnBP) (28%). Phthalate metabolites were detected at medians from 19.5 to 44.4 pg/mg, BPA at 69.9 pg/mg and BPS at 3.5 pg/mg. Significant positive correlations between phthalate metabolites were found which indicated their common sources of exposure. The frequent use of plastics for food storage was strongly associated with mEHP (p = .013) and a weaker association was found for miBP (p = .063). The frequent use of cosmetics during or before pregnancy was associated with levels of phthalate metabolites in hair. More specifically, the use of hair spray before pregnancy was significantly correlated with monobenzyl phthalate (mBzP) (p = .041) and a trend was found for miBP (p = .066). The use of makeup products during pregnancy was strongly associated with miBP (p = .015) and the use of deodorant during pregnancy was inversely associated with mEHP (p = .021). Strong associations came up between mEHP and lower birth weight (Spearman correlation coefficient, r = −0.302, p = .021) and exposure to BPS was associated with increased body mass index of the participants (p = .036). Although data in literature on biomonitoring of the compounds in hair are limited, the findings of this study are promising and in agreement with existing data in hair or urine.