Plastic chemical linked to smaller prefrontal cortex, reduced cognitive ability in rats: Findings demonstrate long-term influence of endocrine-disrupting compounds on brain development -- ScienceDaily

Adult rats that had been exposed before birth and during nursing to a
mixture of chemicals (Phthalates) found in a wide range of consumer products have a
smaller medial prefrontal cortex (mPFC) and perform worse on an
attention-switching task than rats not exposed to the chemicals early in
life. These findings, published in JNeurosci, demonstrate a long-term influence of endocrine-disrupting compounds on brain development.



Daniel G. Kougias, Elli P. Sellinger, Jari Willing, Janice M. Juraska. Perinatal
exposure to an environmentally relevant mixture of phthalates results
in a lower number of neurons and synapses in the medial prefrontal
cortex and decreased cognitive flexibility in adult male and female rats. The Journal of Neuroscience, 2018; 0607-18 DOI: 10.1523/JNEUROSCI.0607-18.2018

What does the environment have to do with autism? | Ensia

The association between total phthalate concentration and non-communicable diseases and chronic inflammation in South Australian urban dwelling men - ScienceDirect

 Objective
To investigate associations between urinary total phthalate concentration, chronic low-grade inflammation and non-communicable diseases in a cohort of South Australian men.
Methods
1504 men aged 39–84 years who provided a urinary sample at the follow-up visit of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study, a randomly-selected group of urban-dwelling, community-based men from Adelaide, Australia (n = 2038; study participation rate: 78.1%). Total phthalate concentration was quantified in fasting morning urine samples. Chronic diseases were assessed through self-report questionnaire or directly measured using standardised clinical and laboratory procedures. Inflammatory biomarkers were assayed by ELISA or spectroscopy. Multivariable linear and logistic regression models were applied to determine associations of log-transformed urinary phthalate concentration with inflammation and chronic disease.
Results
Total phthalates were detected in 99.6% of urinary samples; geometric mean (95% CI) was 114.1 (109.5–118.9) µg/g creatinine. Higher total phthalate levels were associated with higher levels of hs-CRP, IL-6 (all p < 0.05) and TNF-α but not MPO. Urinary total phthalate concentrations were positively associated with cardiovascular disease, type-2-diabetes and hypertension. Comparing extreme quartiles of total phthalate, prevalence ratios were 1.78 (95% CI 1.17 – 2.71, p-trend = 0.001) for cardiovascular disease and 1.84 (95%CI 1.34 – 2.51, p-trend = 0.001) for type-2-diabetes and 1.14 (95%CI 1.01 – 1.29, p-trend = 0.013) for hypertension. Total phthalates and asthma and depression were not significantly associated.
Conclusion
A positive association between total phthalates and cardiovascular disease, type-2-diabetes, hypertension and increased levels of chronic low-grade inflammatory biomarkers was observed in urban-dwelling Australian men."



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Characterization of Adipogenic Activity of House Dust Extracts and Semi-Volatile Indoor Contaminants in 3T3-L1 Cells - Environmental Science & Technology (ACS Publications)

  "Obesity and metabolic disorders are of great societal concern and generate significant human health care costs. Recently, attention has focused on the potential for environmental contaminants to act as metabolic disruptors. This study sought to evaluate the adipogenic activity of indoor house dust extracts and a suite of semivolatile organic chemicals (SVOCs) that are often ubiquitously detected in indoor environments. 3T3-L1 cells were exposed to extracts of indoor dust or individual SVOCs and assessed for triglyceride accumulation and preadipocyte proliferation. Ten of 11 house dust extracts exhibited significant triglyceride accumulation and/or proliferation at environmentally relevant levels (<20 μg of dust/well), and significant adipogenic activity was also exhibited by 28 of the SVOCs. Notably, pyraclostrobin, dibutyl phthalate, tert-butyl-phenyl diphenyl phosphate, and the isopropylated triaryl phosphates (ITPs) exhibited near maximal or supra-maximal triglyceride accumulation relative to the rosiglitazone-induced maximum. The adipogenic activity in house dust occurred at concentrations below EPA estimated child exposure levels, and raises concerns for human health impacts, particularly in children. Our results delineate a novel potential health threat and identify putative causative SVOCs that are likely contributing to this activity."



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Dad's exposure to phthalates in plastics may affect embryonic development

A new study led by environmental health scientist Richard Pilsner at the University of Massachusetts Amherst, one of the first to investigate whether preconception exposures to phthalates in fathers has an effect on reproductive success via embryo quality, found that exposures from select chemicals tested were associated with "a pronounced decrease in blastocyst quality" at an early stage in embryo development.

Phthalates are compounds found in plastics and personal care products that are estimated to be detectable in nearly 100 percent of the U.S. population. The authors believe theirs is the first prospective study to assess associations between paternal exposure to phthalates and embryo quality through the blastocyst stage in humans.

Pilsner and colleagues say their prospective study of 761 oocytes, or immature eggs, from 50 couples undergoing in vitro fertilization (IVF) "provides the first data demonstrating associations between preconception paternal phthalate and phthalate alternatives and embryo development, in a critical step towards our understanding of the paternal contributions to reproductive success." Details appear in the current issue of Human Reproduction from Oxford University Press.

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

The increasing incidence of autism suggests a major environmental influence. Epidemiology has implicated many candidates and genetics many susceptibility genes. Gene/environment interactions in autism were analysed using 206 autism susceptibility genes (ASG's) from the Autworks database to interrogate ∼1 million chemical/gene interactions in the comparative toxicogenomics database. Any bias towards ASG's was statistically determined for each chemical. Many suspect compounds identified in epidemiology, including tetrachlorodibenzodioxin, pesticides, particulate matter, benzo(a)pyrene, heavy metals, valproate, acetaminophen, SSRI's, cocaine, bisphenol A, phthalates, polyhalogenated biphenyls, flame retardants, diesel constituents, terbutaline and oxytocin, inter alia showed a significant degree of bias towards ASG's, as did relevant endogenous agents (retinoids, sex steroids, thyroxine, melatonin, folate, dopamine, serotonin). Numerous other suspected endocrine disruptors (over 100) selectively targeted ASG's including paraquat, atrazine and other pesticides not yet studied in autism and many compounds used in food, cosmetics or household products, including tretinoin, soy phytoestrogens, aspartame, titanium dioxide and sodium fluoride. Autism polymorphisms influence the sensitivity to some of these chemicals and these same genes play an important role in barrier function and control of respiratory cilia sweeping particulate matter from the airways. Pesticides, heavy metals and pollutants also disrupt barrier and/or ciliary function, which is regulated by sex steroids and by bitter/sweet taste receptors. Further epidemiological studies and neurodevelopmental and behavioural research is warranted to determine the relevance of a large number of suspect candidates whose addition to the environment, household, food and cosmetics might be fuelling the autism epidemic in a gene-dependent manner.

Potentially harmful chemicals widespread in household dust

Household dust exposes people to a wide range of toxic chemicals from everyday products, according to a study led by researchers at Milken Institute School of Public Health (Milken Institute SPH) at the George Washington University. The multi-institutional team conducted a first-of-a-kind meta-analysis, compiling data from dust samples collected throughout the United States to identify the top ten toxic chemicals commonly found in dust. They found that DEHP, a chemical belonging to a hazardous class called phthalates, was number one on that list. In addition, the researchers found that phthalates overall were found at the highest levels in dust followed by phenols and flame retardant chemicals."

The barrier, airway particle clearance, placental and detoxification functions of autism susceptibility genes

Even taking problems of diagnosis into account, a five-fold increase in the incidence of autism in recent decades, in the absence of any known changes in the human gene pool suggests a strong environmental influence. Numerous pollutants have been implicated in epidemiological studies, including pesticides, heavy metals, industrial solvents, air pollutants, particulate matter, bisphenol A, phthalates and flame retardants. Many genes have been implicated in autism, some of which are directly related to detoxification processes. Many are also expressed prenatally in the frontal cortex when the effects of such toxins on neurodevelopment are most relevant. To gain access to the foetal brain, toxins must pass placental and blood/brain barriers and access to maternal or children's blood necessitates passage across skin, airway and intestinal barriers. Literature survey of a subset of 206 genes, defined as prime autism susceptibility candidates from an Autworks/Genotator analysis, revealed that most could be related to barrier function at blood/brain, skin, intestinal, placental or other interfaces. These genes were highly enriched in proteome datasets from blood/brain and placental trophoblast barriers and many localised to skin, intestinal, lung, umbilical and placental compartments. Many were also components of the exosomal/transcytosis pathway that is involved in the transfer of compounds across cells themselves, rather than between them. Several are involved in the control of respiratory cilia that sweep mucus and noxious particles from the airways. A key role of autism susceptibility genes may thus relate to their ability to modulate the access of numerous toxins to children, and adults and, during gestation, to the developing foetal brain.

Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003–2010

Background:

Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food.

Objective:

To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the US population.

Methods:

We combined data on 8877 participants from the National Health and Nutrition Examination Survey (NHANES 2003-2010). Using 24-hour dietary recall data, we quantified: 1) fast food intake (percent of total energy intake (TEI) from fast food); 2) fast food-derived fat intake (percent of TEI from fat in fast food); and 3) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression.

Results:

We observed evidence of a positive, dose-response relationship between fast food intake and exposure to phthalates (p-trend<0.0001) but not BPA; participants with high consumption (≥34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than non-consumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend <0.0001). After adjusting for other food groups, ΣDEHPm was associated with grain and other intake, and DiNPm was associated with meat and grain intake.

Conclusion: Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure reduction strategies."



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How a food packaging chemical could lead to weight gain - Medical News Today

"Martin von Bergen, head of the Department of Molecular Systems Biology at the Helmholtz Centre for Environmental Research (UFZ) in Germany, and colleagues found that the chemical di-(2-ethylhexyl)-phthalate (DEHP) led to a hormone imbalance in female mice that triggered weight gain, even when exposed to the chemical in low concentrations."

Phthalates potentially alter levels of a pregnancy hormone that influences sex development

 "Exposure to hormone-altering chemicals called phthalates - which are found in many plastics, foods and personal care products - early in pregnancy is associated with a disruption in an essential pregnancy hormone and adversely affects the masculinization of male genitals in the baby, according to research led by the University of Pittsburgh Graduate School of Public Health."



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Association between urine phthalate levels and poor attentional performance in children with attention-deficit hyperactivity disorder with evidence of dopamine gene-phthalate interaction.

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child's urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

Identification of hot spots of DNA methylation in the adult male adrenal in response to in utero exposure to the ubiquitous endocrine disruptor plasticizer di-(2-ethylhexyl) phthalate.

Exposure to environmental toxicants during fetal development alters gene
expression and promotes disease later in life. Di-(2-ethylhexyl)
phthalate (DEHP) is a plasticizer widely used for the manufacturing of
consumer products. Exposure to DEHP has been associated with obesity,
asthma, and low testosterone levels. In utero exposure of pregnant dams
to DEHP from gestational day 14 until birth resulted in reduced levels
of serum testosterone and aldosterone in the adult male offspring. Since
DEHP is rapidly cleared from the body, the effects observed in the
adult are likely epigenetic in origin. Under the same experimental
conditions, we used reduced-representation bisulfite sequencing to
assess changes in DNA methylation. We identified hot spots of DNA
methylation changes primarily within CpG islands followed by shelf
regions of the genome known to control regional gene expression. We also
identified epigenomic areas responsive to exposure to environmental
levels of DEHP and found the chromosomal region that houses genes
controlling immune responsiveness to be a primary target of DEHP. These
data suggest that DEHP phthalate exposure early in life induces
epigenetic changes that may be linked to altered gene expression and
function in the adult.

Premature infants are exposed to unsafe levels of phthalates in medical products used to save their lives -- ScienceDaily

The chemical, di(2-ethylhexyl)phthalate (DEHP), is used to increase
flexibility of many plastic devices. These products, made from polyvinyl
chloride (PVC), include most intravenous tubing, catheters,
endotracheal tubes, and fluid and blood product bags. DEHP doesn't bind
chemically to PVC, and is able to leach into fluids and body tissues in
contact with it. New Johns Hopkins Bloomberg School of Public Health
research suggests that critically ill preterm infants may be exposed to
DEHP at levels approximately 4,000 to 160,000 times higher than those
believed to be safe. Infants can receive high exposures to DEHP during
weeks to months of treatment in a hospital's neonatal intensive care
unit (NICU).


The results are reported online Nov. 13 date by the Journal of Perinatology.

Food packaging chemicals 'may be harmful to human health' - Medical News Today

The first cause for concern, say the authors, is that certain "known
toxicants" - including formaldehyde, a substance known to cause cancer
- are used legally in food contact materials. Plastic bottles used for carbonated drinks,
for example, usually contain low levels of formaldehyde.

Another point the authors make is that hormone production-disrupting
chemicals, such as bisphenol A (BPA), tributyltin, triclosan and
phthalates, can also be present in FCMs.

Urinary Phthalates and Increased Insulin Resistance in Adolescents

BACKGROUND: Di-2-ethylhexylphthalate (DEHP) is an environmental chemical commonly found in processed foods. Phthalate exposures, in particular to DEHP, have been associated with insulin resistance in adults, but have not been studied in adolescents.

METHODS: Using cross-sectional data from 766 fasting 12- to 19-year-olds in the 2003–2008 NHANES, we examined associations of phthalate metabolites with continuous and categorical measures of homeostatic model assessment of insulin resistance (HOMA-IR).

RESULTS: Controlling for demographic and behavioral factors, diet, continuous age, BMI category, and urinary creatinine, for each log (roughly threefold) increase in DEHP metabolites, a 0.27 increase (95% confidence interval 0.14–0.40; P < .001) in HOMA-IR was identified. Compared with the first tertile of DEHP metabolite in the study population (14.5% insulin resistant), the third tertile had 21.6% prevalence (95% confidence interval 17.2%–26.0%; P = .02). Associations persisted despite controlling for bisphenol A, another endocrine-disrupting chemical commonly found in foods, and HOMA-IR and insulin resistance were not significantly associated with metabolites of lower molecular weight phthalates commonly found in cosmetics and other personal care products.

CONCLUSIONS: Urinary DEHP concentrations were associated with increased insulin resistance in this cross-sectional study of adolescents. This study cannot rule out the possibility that insulin-resistant children ingest food with higher phthalate content, or that insulin-resistant children excrete more DEHP.

Food contaminants worsen metabolic problems in obese mice

 "Certain food contaminants are suspected of triggering metabolic disorders, or of worsening them, particularly when they accompany a high-fat diet. In order to get a better understanding of these effects, researchers from the Inserm cardiovascular, metabolism, diabetology and nutrition unit (U1060 " Laboratoire de recherche en cardiovasculaire, métabolisme, diabétologie et nutrition " Inserm/Inra/Université Lyon 1) introduced a "cocktail" of contaminants mixed with low doses of dioxin, PCB, bisphenol A and phtalates into the feeding of mice that had already been rendered obese by a high-fat diet. The results show that metabolic changes occur in these mice, but that the effects differ depending on the gender. Females appeared to be more affected. Their obesity-induced glucose intolerance worsened and their estrogen pathway was altered."

Phthalates: Study links chemicals widely found in plastics, processed food to elevated blood pressure in children, teens

 "Plastic additives known as phthalates are odorless, colorless and just about everywhere: They turn up in flooring, plastic cups, beach balls, plastic wrap, intravenous tubing and—according to the Centers for Disease Control and Prevention—the bodies of most Americans. Once perceived as harmless, phthalates have come under increasing scrutiny. A growing collection of evidence suggests dietary exposure to phthalates (which can leech from packaging and mix with food) may cause significant metabolic and hormonal abnormalities, especially during early development."

Researchers find industrial chemicals in food samples

 "Researchers at The University of Texas Health Science Center at Houston (UTHealth) have discovered phthalates, industrial chemicals, in common foods purchased in the United States. Phthalates can be found in a variety of products and food packaging material, child-care articles and medical devices."

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Contaminated diet contributes to exposure to endocrine-disrupting chemicals: Phthalates and BPA

"According to a study published February 27 in the Nature Journal of Exposure Science and Environmental Epidemiology, we may be exposed to these chemicals in our diet, even if our diet is organic and we prepare, cook, and store foods in non-plastic containers. Children may be most vulnerable."

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