PLOS ONE: [filterJournals=PLoSONE, q=, filterSubjects=Phthalates, session=9056e35f8bc8bea90c132bd18f4c1971]

Structured expert judgement approach of the health impact of various chemicals and classes of chemicals

2024-06-24T14:00:00Z

by Deniz Marti, David Hanrahan, Ernesto Sanchez-Triana, Mona Wells, Lilian Corra, Howard Hu, Patrick N. Breysse, Amalia Laborde, Jack Caravanos, Roberto Bertollini, Kate Porterfield, Richard Fuller

Introduction

Chemical contamination and pollution are an ongoing threat to human health and the environment. The concern over the consequences of chemical exposures at the global level continues to grow. Because resources are constrained, there is a need to prioritize interventions focused on the greatest health impact. Data, especially related to chemical exposures, are rarely available for most substances of concern, and alternate methods to evaluate their impact are needed.

Structured expert judgment (SEJ) process

A Structured Expert Judgment (Research Outreach, 2021) process was performed to provide plausible estimates of health impacts for 16 commonly found pollutants: asbestos, arsenic, benzene, chromium, cadmium, dioxins, fluoride, highly hazardous pesticides (HHPs), lead, mercury, polycyclic-aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), Per- and Polyfluorinated Substances (PFAs), phthalates, endocrine disrupting chemicals (EDCs), and brominated flame retardants (BRFs). This process, undertaken by sector experts, weighed individual estimations of the probable global health scale health impacts of each pollutant using objective estimates of the expert opinions’ statistical accuracy and informativeness.

Main findings

The foremost substances, in terms of mean projected annual total deaths, were lead, asbestos, arsenic, and HHPs. Lead surpasses the others by a large margin, with an estimated median value of 1.7 million deaths annually. The three other substances averaged between 136,000 and 274,000 deaths per year. Of the 12 other chemicals evaluated, none reached an estimated annual death count exceeding 100,000. These findings underscore the importance of prioritizing available resources on reducing and remediating the impacts of these key pollutants.

Range of health impacts

Based on the evidence available, experts concluded some of the more notorious chemical pollutants, such as PCBs and dioxin, do not result in high levels of human health impact from a global scale perspective. However, the chemical toxicity of some compounds released in recent decades, such as Endocrine Disrupters and PFAs, cannot be ignored, even if current impacts are limited. Moreover, the impact of some chemicals may be disproportionately large in some geographic areas. Continued research and monitoring are essential; and a preventative approach is needed for chemicals.

Future directions

These results, and potential similar analyses of other chemicals, are provided as inputs to ongoing discussions about priority setting for global chemicals and pollution management. Furthermore, we suggest that this SEJ process be repeated periodically as new information becomes available.

Relationship between phthalates exposures and metabolic dysfunction-associated fatty liver disease in United States adults

2024-04-19T14:00:00Z

by Junhao Sun, Siqi Yang, Yue Zhang, Wenzhi Xiang, Xiubo Jiang

As a new definition for the evidence of hepatic steatosis and metabolic dysfunctions, the relationship between phthalates (PAEs) and metabolic dysfunction-associated fatty liver disease (MAFLD) remains virtually unexplored. This study included 3,137 adults from the National Health and Nutrition Examination Survey spanning 2007–2018. The diagnosis of MAFLD depended on the US Fatty Liver Index (US FLI) and evidence of metabolic dysregulation. Eleven metabolites of PAEs were included in the study. Poisson regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were used to assess the associations between phthalate metabolites and MAFLD. After adjusting for potential confounders, Poisson regression analysis showed that mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate were generally significant positively associated with MAFLD (P<0.05). Furthermore, the WQS index constructed for the eleven phthalates was significantly related to MAFLD (OR:1.43; 95%CI: 1.20, 1.70), MEHHP (33.30%), MEP (20.84%), MECPP (15.43%), and mono-isobutyl phthalate (11.78%) contributing the most. This study suggests that exposure to phthalates, individually or in combination, may be associated with an increased risk of MAFLD.

Prenatal phthalate exposure and sex steroid hormones in newborns: Taiwan Maternal and Infant Cohort Study

2024-03-14T14:00:00Z

by Chin-Li Lu, Hui-Ju Wen, Mei-Lien Chen, Chien-Wen Sun, Chia-Jung Hsieh, Ming-Tsang Wu, Shu-Li Wang, TMICS study group

Background

Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear.

Object

This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD).

Methods

In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012–2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns’ AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD.

Results

Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns’ AGDs.

Conclusions

Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure.

Bisphenol-A and phthalate metabolism in children with neurodevelopmental disorders

2023-09-13T14:00:00Z

by T. Peter Stein, Margaret D. Schluter, Robert A. Steer, Xue Ming

Background

The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

Hypothesis

Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

Methods

We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP.

Results

(1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends.

Conclusion

ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant.

Exposure to the non-phthalate plasticizer di-heptyl succinate is less disruptive to C57bl/6N mouse recovery from a myocardial infarction than DEHP, TOTM or related di-octyl succinate

2023-07-13T14:00:00Z

by Adam Schwendt, Joey-Bahige Chammas, Milan Maric, Jim A. Nicell, Richard Leask, Lorraine E. Chalifour

Phthalate plasticizers are incorporated into plastics to make them soft and malleable, but are known to leach out of the final product into their surroundings with potential detrimental effects to human and ecological health. The replacement of widely-used phthalate plasticizers, such as di-ethylhexyl phthalate (DEHP), that are of known toxicity, by the commercially-available alternative Tris(2-ethylhexyl) tri-mellitate (TOTM) is increasing. Additionally, several newly designed “green” plasticizers, including di-heptyl succinate (DHPS) and di-octyl succinate (DOS) have been identified as potential replacements. However, the impact of plasticizer exposure from medical devices on patient recovery is unknown and, moreover, the safety of TOTM, DHPS, and DOS is not well established in the context of patient recovery. To study the direct effect of clinically based chemical exposures, we exposed C57bl/6 N male and female mice to DEHP, TOTM, DOS, and DHPS during recovery from cardiac surgery and assessed survival, cardiac structure and function, immune cell infiltration into the cardiac wound and activation of the NLRP3 inflammasome. Male, but not female, mice treated in vivo with DEHP and TOTM had greater cardiac dilation, reduced cardiac function, increased infiltration of neutrophils, monocytes, and macrophages and increased expression of inflammasome receptors and effectors, thereby suggesting impaired recovery in exposed mice. In contrast, no impact was detected in female mice and male mice exposed to DOS and DHPS. To examine the direct effects in cells involved in wound healing, we treated human THP-1 macrophages with the plasticizers in vitro and found DEHP induced greater NLRP3 expression and activation. These results suggest that replacing current plasticizers with non-phthalate-based plasticizers may improve patient recovery, especially in the male population. In our assessment, DHPS is a promising possibility for a non-toxic biocompatible plasticizer.

Contaminant occurrence, distribution and ecological risk assessment of phthalate esters in the Persian Gulf

2023-07-07T14:00:00Z

by Maria Khishdost, Sina Dobaradaran, Gholamreza Goudarzi, Afshin Takdastan, Ali Akbar Babaei

Due to the increasing population of the world, the presence of harmful compounds, especially phthalate esters (PAEs), are one of the important problems of environmental pollution. These compounds are known as carcinogenic compounds and Endocrine-disrupting chemicals (EDCs) for humans. In this study, the occurrence of PAEs and the evaluation of its ecological risks were carried out in the Persian Gulf. Water samples were collected from two industrial sites, a rural site and an urban site. Samples were analyzed using magnetic solid phase extraction (MSPE) and gas chromatography-mass spectrometry (GC/MS) technique to measure seven PAEs including Di(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), diethyl phthalate (DEP), dibutyl phthalate (DBP), Dimethyl phthalate (DMP), di-n-octyl phthalate (DNOP), and Di-iso-butyl phthalate (DIBP). The BBP was not detected in any of the samples. The total concentration of six PAEs (Σ6PAEs) ranged from 7.23 to 23.7 μg/L, with a mean concentration of 13.7μg/L. The potential ecological risk of each target PAEs was evaluated by using the risk quotient (RQ) method in seawater samples, and the relative results declined in the sequence of DEHP >DIBP > DBP > DEP > DMP in examined water samples. DEHP had a high risk to algae, crustaceans and fish at all sites. While DMP and DEP showed lower risk for all mentioned trophic levels. The results of this study will be helpful for the implementation of effective control measures and remedial strategies for PAEs pollution in the Persian Gulf.

Childhood exposures to environmental chemicals and neurodevelopmental outcomes in congenital heart disease

2022-11-17T14:00:00Z

by J. William Gaynor, Nancy B. Burnham, Richard F. Ittenbach, Marsha Gerdes, Judy C. Bernbaum, Elaine Zackai, Daniel J. Licht, William W. Russell, Erin E. Zullo, Thomas Miller, Hakon Hakonarson, Kayan A. Clarke, Gail P. Jarvik, Antonia M. Calafat, Asa Bradman, David C. Bellinger, Frederick M. Henretig, Eric S. Coker

Background

Children with congenital heart defects have an increased risk of neurodevelopmental disability. The impact of environmental chemical exposures during daily life on neurodevelopmental outcomes in toddlers with congenital heart defects is unknown.

Methods

This prospective study investigated the impacts of early childhood exposure to mixtures of environmental chemicals on neurodevelopmental outcomes after cardiac surgery. Outcomes were assessed at 18 months of age using The Bayley Scales of Infant and Toddler Development-III. Urinary concentrations of exposure biomarkers of pesticides, phenols, parabens, and phthalates, and blood levels of lead, mercury, and nicotine were measured at the same time point. Bayesian profile regression and weighted quantile sum regression were utilized to assess associations between mixtures of biomarkers and neurodevelopmental scores.

Results

One-hundred and forty infants were enrolled, and 110 (79%) returned at 18 months of age. Six biomarker exposure clusters were identified from the Bayesian profile regression analysis; and the pattern was driven by 15 of the 30 biomarkers, most notably 13 phthalate biomarkers. Children in the highest exposure cluster had significantly lower adjusted language scores by -9.41 points (95%CI: -17.2, -1.7) and adjusted motor scores by -4.9 points (-9.5, -0.4) compared to the lowest exposure. Weighted quantile sum regression modeling for the overall exposure-response relationship showed a significantly lower adjusted motor score (β = -2.8 points [2.5^th and 97.5^th percentile: -6.0, -0.6]). The weighted quantile sum regression index weights for several phthalates, one paraben, and one phenol suggest their relevance for poorer neurodevelopmental outcomes.

Conclusions

Like other children, infants with congenital heart defects are exposed to complex mixtures of environmental chemicals in daily life. Higher exposure biomarker concentrations were associated with significantly worse performance for language and motor skills in this population.

Trimester-specific phthalate exposures in pregnancy are associated with circulating metabolites in children

2022-08-30T14:00:00Z

by Jaclyn M. Goodrich, Lu Tang, Yanelli R. Carmona, Jennifer L. Meijer, Wei Perng, Deborah J. Watkins, John D. Meeker, Adriana Mercado-García, Alejandra Cantoral, Peter X. Song, Martha M. Téllez-Rojo, Karen E. Peterson

Background

Prenatal phthalates exposures have been related to adiposity in peripuberty in a sex-specific fashion. Untargeted metabolomics analysis to assess circulating metabolites offers the potential to characterize biochemical pathways by which early life exposures influence the development of cardiometabolic risk during childhood and adolescence, prior to becoming evident in clinical markers.

Methods

Among mother-child dyads from the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, we measured 9 phthalate metabolites and bisphenol A in maternal spot urine samples obtained during each trimester of pregnancy, corrected for urinary specific gravity and natural log-transformed. In 110 boys and 124 girls aged 8–14 years, we used a mass-spectrometry based untargeted metabolomics platform to measure fasting serum metabolites, yielding 572 annotated metabolites. We estimated the associations between trimester-specific urinary toxicants and each serum metabolite, among all children or stratified by sex and adjusting for child age, BMI z-score, and pubertal onset. We accounted for multiple comparisons using a 10% false discovery rate (q<0.1).

Results

Associations between exposures and metabolites were observed among all children and in sex-stratified analyses (q<0.1). First trimester MEP, MiBP, and MCPP were associated with decreased 2-deoxy-D-glucose among all children. Among girls, third trimester concentrations of MECPP, MEHHP, MEHP, and MCPP were associated with 15, 13, 1, and 10 metabolites, respectively, including decreased choline and increased acylcarnitines and saturated FAs (FA). Among boys, third trimester MIBP was positively associated with 9 features including long chain saturated FAs, and second trimester MBzP was inversely associated with thyroxine.

Conclusions

Metabolomics biomarkers may reflect sex- and exposure timing-specific responses to prenatal phthalate exposures manifesting in childhood that may not be detected using standard clinical markers of cardiometabolic risk.

Maternal occupational exposures and fetal growth in a Spanish birth cohort

2022-04-07T14:00:00Z

by Jennifer Ish, David Gimeno Ruiz de Porras, Elaine Symanski, Ferran Ballester, Maribel Casas, George L. Delclos, Mònica Guxens, Jesús Ibarluzea, Carmen Iñiguez, Loreto Santa-Marina, Michael D. Swartz, Kristina W. Whitworth

While the epidemiologic literature suggests certain maternal occupational exposures may be associated with reduced measures of size at birth, the occupational literature employing fetal biometry data to assess fetal growth is sparse. The present study examines associations between maternal occupational exposures and ultrasound-measured fetal growth. We included 1,739 singleton pregnancies from the INfancia y Medio Ambiente (INMA) project (2003-2008). At 32 weeks of pregnancy, interviewers ascertained mothers’ employment status and assessed job-related physical loads, work schedules, and job strain during pregnancy. Job titles were linked to a job-exposure matrix to estimate exposure to 10 endocrine disrupting chemical (EDC) groups. We calculated z-scores from longitudinal growth curves representing trajectories from 0-12, 12-20 and 20-34 gestational weeks for abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW). Linear mixed models clustered by IMNA region (i.e., Gipuzkoa, Sabadell, Valencia) were used to examine associations between occupational exposures and fetal growth. Effect estimates are presented as percentage change in fetal growth. There was limited evidence of associations between work-related non-chemical stressors and fetal growth. We observed associations of similar magnitude between multiple EDC groups and decreased EFW trajectories during 20-34 gestational weeks (phthalates: -1.4% [-3.5, 0.6%]; alkylphenolic compounds (APCs): -1.1% [-2.3, 0.1%]; miscellaneous chemicals: -1.5% [-3.7, 0.8%]), while miscellaneous chemicals were associated with increased BPD from 12-20 weeks (2.1% [0.8, 3.5%]). Notably, 67% of women exposed to phthalates were hairdressers; 68% of women exposed to APCs worked as domestic cleaners. In conclusion, we found limited evidence that maternal occupational exposures impact fetal growth. Further research should consider the combined impact of multiple workplace exposures.

Phthalate exposure among U.S. college-aged women: Biomonitoring in an undergraduate student cohort (2016-2017) and trends from the National Health and Examination Survey (NHANES, 2005-2016)

2022-02-11T14:00:00Z

by Barbara A. Beckingham, Kerry Wischusen, Joanna P. Walker

Importance

Phthalates are ubiquitous and many are known or suspected human reproductive and endocrine-disrupting toxicants. A data gap exists in reporting on biomonitoring of phthalate biomarkers in college-aged adults.

Objective

To analyze phthalate exposure in a cross-sectional sample of female college students using urinary phthalate metabolite concentrations and compare to reference populations including college-aged women sampled in the National Health and Nutrition Examination Survey (NHANES).

Methods

Nine monoester phthalate metabolites were analyzed in spot urine collected from 215 female undergraduates (age 18–22, 2016–2017) at a public university in Charleston, SC USA and a subset of participants completed a questionnaire detailing demographics and behaviors including personal care and cosmetic product use (e.g. in the past 6 or 24 hrs). Urine specific gravity was used to assess effect of urine dilution. Phthalate metabolite concentrations were compared to reference populations and the temporal trends of the same age-group in the National Health and Nutrition Examination Survey (NHANES) were analyzed.

Results

Total urinary phthalate metabolite concentrations in individuals ranged three orders of magnitude (geometric mean 56.6 ng/mL, IQR 26.6–114 ng/mL). A third of urine samples had relatively high urine specific gravity levels indicating potential dehydration status. All geometric mean concentrations were similar to the U.S. female population in the most recent NHANES cycle (2015–2016) except for MEP and mono-isobutyl phthalate (MiBP). Relatively low MEP and MiBP may be explained by a time trend of declining MEP in the general U.S. population, the sociocultural character of this cohort, and the time of day of spot sampling in evening. NHANES data indicate a significant effect of sample timing on phthalate metabolite concentrations and decline in most, but not all, phthalate metabolites sampled in women aged 18–22 years over the decade (2005–2016).

Significance

This study reports phthalate metabolites in college-aged women, an understudied group, emphasizes the benefit of survey information for interpreting biomonitoring data, and is a useful case study for communicating phthalate chemical exposure risks to college students.

Establishing a protocol for the compatibilities of closed-system transfer devices with multiple chemotherapy drugs under simulated clinical conditions

2021-09-28T14:00:00Z

by Shao-Chin Chiang, Mandy Shen, Chen-Chia Lin, Hui-Ping Chang

Closed-system drug transfer devices (CSTDs) are used to prevent occupational exposure to hazardous drugs in health care providers. They are considered Class II medical devices by the US FDA and are cleared but not approved before marketing. While compatibility tests are conducted by CSTD manufacturers, the procuring institution needs to consider performing its own studies before buying these devices. Herein we tested the compatibility of the components of the Needleless^® DualGuard CSTD system (vial access clips, vial access spikes, and administration adaptors) with 10 antineoplastic drugs, under simulated clinical conditions, including compounding and administration, and examined drug potency maintenance, plasticizer migration, and device functionality. All drugs maintained potency within 5%. Diisononyl phthalate leakage was observed from the administration adaptors for paclitaxel and concentrated etoposide solution. In addition, white particles were discovered in CSTDs storing busulfan solution and small cracks were observed on devices which stored melphalan. Thus, it was concluded that even in simulated clinical conditions, instead of extreme conditions, there are still concerns regarding the efficacy and safety of CSTD components. The methodology may be used to implement and detect possible interactions between antineoplastic agents and CSTD components before procurement.

Deterioration of modern concrete structures and asphalt pavements by respiratory action and trace quantities of organic matter

2021-05-13T14:00:00Z

by Akihiro Moriyoshi, Eiji Shibata, Masahito Natsuhara, Kiyoshi Sakai, Takashi Kondo, Akihiko Kasahara

In concrete structures (concrete), damage from cracks, deterioration, amorphization, and delamination occur in some structures, causing disaggregation (concrete changed to very fine particles) and hollowing out of the concrete. In concrete pavements, damage from large amounts of pop-out of aggregate occurs from the surface of the concrete pavement 4–5 hours after spraying of snow melting agent on the surface of the pavement. The damage from disaggregation, blistering, cracks, and peeling-off of a surface course have also been observed in asphalt runways and highways. The damage from disaggregation, cracks and pop-out of aggregate in asphalt pavements and concrete structures have long been seen as strange and unexpected and have defied explanation. As a result of examinations in various experiments, it was concluded that all of the unexplained kinds of damage of both asphalt pavements and concrete structures were caused by Trace Quantities of Organic Matter (TQOM), Air Entrained (AE) water reducing agent in air and/or cement, and surfactant in snow melting agent. The emission sources of TQOM and these organic substances were also identified by chemical analysis for these unexpected and unexplained phenomena. The TQOM includes phthalate compounds (phthalates in the following), amine compounds, phosphate compounds, snow melting agent and Sodium Polyoxyethylene Nonyl phenyl Ether Sulfate (SPNES). SPNES is a surfactant in windshield washer fluid for automobiles. We found that the water content and content of organic matter in damaged asphalt pavements and concrete structures are also important indicators for the damage. Further, a new evaluation method for amorphization was proposed in this study and it appears suitable for evaluating the safety of concrete structures along roads which were exposed to TQOM in severely air-polluted environments.

Sentinels of synthetics – a comparison of phthalate exposure between common bottlenose dolphins (Tursiops truncatus) and human reference populations

2020-10-15T14:00:00Z

by Leslie B. Hart, Miranda K. Dziobak, Emily C. Pisarski, Edward F. Wirth, Randall S. Wells

Phthalates are chemical esters used as additives in common consumer goods, such as plastics, household cleaners, and personal care products. Phthalates are not chemically bound to the items to which they are added and can easily leach into the surrounding environment. Anthropogenic drivers, such as coastal plastic pollution and wastewater runoff, increase the exposure potential for coastal marine fauna. Phthalate exposure in free-ranging bottlenose dolphins has been the focus of recent study, with indications of heightened exposure to certain phthalate compounds. The objective of this study was to compare urinary phthalate metabolite concentrations among bottlenose dolphins (Tursiops truncatus) sampled in Sarasota Bay, FL, to levels reported in human samples collected as part of the Centers for Disease Control and Prevention’s (CDC) National Health and Nutrition Examination Survey (NHANES). Monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) were the most prevalent metabolites detected in dolphin urine (n = 51; MEP = 29.41%; MEHP = 54.90%). The geometric mean (GM) concentration of MEP was significantly lower for dolphins (GM = 4.51 ng/mL; 95% CI: 2.77–7.34 ng/mL) compared to humans (p<0.05), while dolphin concentrations of MEHP (GM = 4.57 ng/mL; 95% CI: 2.37–8.80 ng/mL) were significantly higher than levels reported in NHANES (p<0.05). Health impacts to bottlenose dolphins resulting from elevated exposure to the MEHP parent compound (diethyl-2-ethylhexyl phthalate, DEHP) are currently unknown. However, given the evidence of endocrine disruption, reproductive impairment, and abnormal development in humans, pursuing investigations of potential health effects in exposed bottlenose dolphins would be warranted.

Association between dietary contribution of ultra-processed foods and urinary concentrations of phthalates and bisphenol in a nationally representative sample of the US population aged 6 years and older

2020-07-31T14:00:00Z

by Eurídice Martínez Steele, Neha Khandpur, Maria Laura da Costa Louzada, Carlos Augusto Monteiro

Ultra-processed food consumption has been associated with several health outcomes such as obesity, hypertension, cardiovascular disease and cancer. The deleterious nutrient profile of these products, and the presence of food additives, neoformed contaminants and contact materials such as phthalates and bisphenol may be some of the potential pathways through which ultra-processed food influences disease outcomes. The aim of this study was to examine the association between dietary contribution of ultra-processed foods and urinary biomarker concentrations of parent compounds or their metabolites including Di(2-ethylhexyl) phthalate (ΣDEHP), Di-isononyl phthalate (ΣDiNP), Monocarboxynonyl phthalate (mCNP), Mono (3-carboxypropyl) phthalate (mCPP), Monobenzyl phthalate (mBzP), Bisphenol A (BPA), Bisphenol F (BPF) and Bisphenol S (BPS), in the US. Participants from the cross-sectional 2009–2016 National Health and Nutrition Examination Survey, aged 6+ years, with urinary measures and with one 24-hour dietary recall were included in the study. Ultra-processed foods were identified based on the NOVA classification system, a four-group food classification based on the extent and purpose of industrial food processing. Linear regression was used to compare average urinary creatinine-standardized concentrations across quintiles of energy contribution of ultra-processed foods. Models incorporated survey sample weights and were adjusted for different sociodemographic and life-style variables. Adjusted geometric means of ΣDiNP, mCNP, mCPP, mBzP and BPF increased monotonically from the lowest to the highest quintile of ultra-processed food consumption. As both phthalates/bisphenol and ultra-processed foods have been previously associated with insulin resistance, diabetes, general/abdominal obesity and hypertension, our results suggest the possibility of contact materials in ultra-processed foods as one link between ultra-processed food and these health outcomes. Future studies could confirm findings and further explore these mechanisms of action.

Automated identification of multinucleated germ cells with U-Net

2020-07-09T14:00:00Z

by Samuel Bell, Andras Zsom, Justin Conley, Daniel Spade

Phthalic acid esters (phthalates) are male reproductive toxicants, which exert their most potent toxicity during fetal development. In the fetal rat, exposure to phthalates reduces testosterone biosynthesis, alters the development of seminiferous cords and other male reproductive tissues, and induces the formation of abnormal multinucleated germ cells (MNGs). Identification of MNGs is a time-intensive process, and it requires specialized training to identify MNGs in histological sections. As a result, MNGs are not routinely quantified in phthalate toxicity experiments. In order to speed up and standardize this process, we have developed an improved method for automated detection of MNGs. Using hand-labeled histological section images with human-identified MNGs, we trained a convolutional neural network with a U-Net architecture to identify MNGs on unlabeled images. With unseen hand-labeled images not used in model training, we assessed the performance of the model, using five different configurations of the data. On average, the model reached near human accuracy, and in the best model, it exceeded it. The use of automated image analysis will allow data on this histopathological endpoint to be more readily collected for analysis of phthalate toxicity. Our trained model application code is available for download at github.com/brown-ccv/mngcount.