Auf dieser Seite finden Sie Studien, die die gesundheitsschädigende Wirkung von Plastik untersuchen. Zu jeder Studie finden Sie einen Link, der Sie zu dem kompletten Text führt.
This study investigates whether plastic substances found in maternal blood have negative effects on the health of the fetus or the infant. mehr
Exposure to dioxins and polychlorinated biphenyls (PCBs) during pregnancy and breastfeeding may result in adverse health effects in children. Prenatal exposure is determined by the concentrations of dioxins and PCBs in maternal blood, which reflect the body burden obtained by long term dietary exposure. The aims of this study were
Dietary exposure to dioxins (sum of toxic equivalents (TEQs) from dioxin-like (dl) compounds) and PCB-153 in 83,524 pregnant women (gestational weeks 17–22) who participated in the Norwegian Mother and Child Cohort Study (MoBa) during the years 2002–2009 was calculated based on a food frequency questionnaire (FFQ) and a database of dioxin and PCB concentrations in Norwegian food. The median (interquartile range, IQR) intake of PCB-153 (marker of ndl-PCBs) was 0.81 (0.77) ng/kg bw/day. For dioxins and dioxin-like PCBs, the median (IQR) intake was 0.56 (0.37) pg TEQ/kg bw/day.
Moreover, 2.3% of the participants had intakes exceeding the tolerable weekly intake (TWI) of 14 pg TEQ/kg bw/week. Multiple regression analysis showed that dietary exposure was positively associated with maternal age, maternal education, weight gain during pregnancy, being a student, and alcohol consumption during pregnancy and negatively associated with pre-pregnancy BMI and smoking. A high dietary exposure to PCB-153 or dl-compounds (TEQ) was mainly explained by the consumption of seagull eggs and/or pate with fish liver and roe. Women who according to Norwegian recommendations avoid these food items generally do not have dietary exposure above the tolerable intake of dioxins and dl-PCBs.
The fear of exposure to certain substances such as organophosphates, pesticides or bisphenol A is getting bigger. In this study, urine was tested for these substances by three different groups of pregnant women. mehr
Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples representing 110 pregnant women who participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004. Daily intakes were estimated from urinary data and compared with reference doses (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA concentration (4.50 microg/L) than the pregnant women in the Generation R Study (Generation R) in the Netherlands and the National Health and Nutrition Examination Survey (NHANES) in the United States.
The mean concentration of total DAP metabolites (24.20 microg/L) in MoBa women was higher than that in NHANES women but lower than that in Generation R women. The diethyl phthalate metabolite mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three studies, with the mean concentrations of greater than 300 microg/L. The MoBa and Generation R women had higher mean concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated average daily intakes of BPA, chlorpyrifos/chlorpyrifos-methyl and phthalates in MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels of metabolites in the MoBa participants may have been from intake via pesticide residues in food (organophosphates), consumption of canned food, especially fish/seafood (BPA), and use of personal care products (selected phthalates).
This article deals with the question of whether there is a connection between the prenatal burden of phthalates and the health of the newborn. mehr
Phthalates are developmental and reproductive toxicants for the fetus in pregnant rodents, and the ability of phthalates to penetrate the placenta have been reported. The aims of this study were to evaluate the association between maternal urine excretion, the exposure of fetus to phthalates in amniotic fluid, and the health of newborns. Amniotic fluid and urine samples from pregnant women were collected to measure five phthalate monoesters using liquid chromatography/tandem mass spectrometry (LC/MS-MS) and the newborns’ birth weight, gestational age, and anogenital distance (AGD) were collected.
The median levels of three phthalate monoesters in urine and amniotic fluid were 78.4 and 85.2 ng/mL monobutyl phthalate (MBP); 24.9 and 22.8 ng/mL mono-(2-ethylhexyl) phthalate (MEHP); 19.8 and Not Detected monoethyl phthalate (MEP). We found a significant positive correlation only between creatinine adjusted urinary 5MBP6 and amniotic fluid 5MBP6 (R2 = 0.156, p < 0.05) in all infants and, only in female infants, a significantly negative correlation between amniotic fluid MBP, 5AGD6 (R = − 0.31, p < 0.06), and the anogenital index adjusted by birth weight (AGI-W) (R = − 0.32, p < 0.05). Although the influence of prenatal di-n-butyl phthalate (DBP) exposure on the endocrinology and physiology of the fetus is still a puzzle, our data clearly show that in utero exposure to phthalates in general has anti-androgenic effects on the fetus.
Phthalate exposure is known to affect neuronal development. Here it was examined whether there is a connection between prenatal phthalate exposure and behavior at the age of 4-9 years. mehr
Experimental and observational studies have reported biological consequences of phthalate exposure relevant to neurodevelopment.
Our goal was to examine the association of prenatal phthalate exposure with behavior and executive functioning at 4-9 years of age.
The Mount Sinai Children's Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urines were collected and analyzed for phthalate metabolites. Children (n = 188, n = 365 visits) were assessed for cognitive and behavioral development between the ages of 4 and 9 years.
In multivariate adjusted models, increased loge concentrations of low molecular weight (LMW) phthalate metabolites were associated with poorer scores on the aggression [beta = 1.24; 95% confidence interval (CI), 0.15- 2.34], conduct problems (beta = 2.40; 95% CI, 1.34-3.46), attention problems (beta = 1.29; 95% CI, 0.16- 2.41), and depression (beta = 1.18; 95% CI, 0.11-2.24) clinical scales; and externalizing problems (beta = 1.75; 95% CI, 0.61-2.88) and behavioral symptom index (beta = 1.55; 95% CI, 0.39-2.71) composite scales. Increased loge concentrations of LMW phthalates were also associated with poorer scores on the global executive composite index (beta = 1.23; 95% CI, 0.09-2.36) and the emotional control scale (beta = 1.33; 95% CI, 0.18- 2.49).
Behavioral domains adversely associated with prenatal exposure to LMW phthalates in our study are commonly found to be affected in children clinically diagnosed with conduct or attention deficit hyperactivity disorders.
In Puerto Rico, the highest incidence of premature breast development in girls under the age of 8 has been recorded. This study examines whether there is a relationship between the estrogenic effects of some plastics and this phenomenon. mehr
Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico.
This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors.
This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.
This study addresses EEDCs (estrogenic, endocrine-disrupting chemicals). These can cause developmental disorders in mammals. mehr
Plastics and pesticides are examples of products that contain oestrogenic endocrine-disrupting chemicals, or EEDCs, which can interfere with mammalian development by mimicking the action of the sex hormone oestradiol. For instance, the exposure of developing rodents to high doses of EEDCs advances puberty and alters their reproductive function. Low environmental doses of EEDCs may also affect development in humans.
Effects have become apparent in humans over the past half century that are consistent with those seen in animals after exposure to high doses of EEDCs, such as an increase in genital abnormality in boys and earlier sexual maturation in girls. Here we show that exposing female mouse fetuses to an EEDC at a dose that is within the range typical of the environmental exposure of humans alters the postnatal growth rate and brings on early puberty in these mice.
This study aims to give an overview of the effects of bisphenol A in animals and humans, as well as its effects on the environment. mehr
Bisphenol A (BPA), is an industrially important compound and is widely used for the production of polycarbonates and other plastics. Over the past few years, there have been many issues raised all over the world on the use of BPA. BPA is known to possess estrogenic activities; hence, it mimics the role of estrogen once it enters living systems. Thus, it has been placed in the category of compounds called endocrine disruptors. It can cause damage to reproductive organs, thyroid gland, and brain tissues at developmental stages, and most recently it has also been linked to cancer development in humans.
Here, in this review, we aim to summarize the various effects of BPA on humans and animals, and at the same time we wish to throw some light on the emerging field of biodegradation of BPA in the natural environment. A few studies conducted recently have tried to isolate BPA-degrading microorganisms from various sites, like water bodies receiving wastes from industries, landfills, etc. In the present scenario, with huge controversies on the use of BPA, we emphasize on bridging the gap between studies, aiming at finding the damage caused by BPA, and the studies which aim at the safe removal of BPA from the environment, with the help of naturally occurring microbes. Once this gap is filled, we will be able to find a way which will allow the use of BPA in manufacturing plastics, without its accumulation in the environment.
In many products, bisphenol A, considered very high-risk, it was replaced by bisphenol S. This study compares these two with respect to many factors. mehr
For several decades, people have been in contact with bisphenol A (BPA) primarily through their diet. Nowadays it is gradually replaced by an analogue, bisphenol S (BPS). In this study, we compared the effects of these two bisphenols in parallel with the positive control diethylstilbestrol (DES) on different hepatocyte cell lines. Using a cellular impedance system we have shown that BPS is less cytotoxic than BPA in acute and chronic conditions. We have also demonstrated that, contrary to BPA, BPS is not able to induce an increase in intracellular lipid and does not activate the PXR receptor which is known to be involved in part, in this process. In parallel, it failed to modulate the expression of CYP3A4 and CYP2B6, the drug transporter ABCB1 and other lipid metabolism genes (FASN, PLIN). However, it appears to have a weak effect on GSTA4 protein expression and on the Erk1/2 pathway.
In conclusion, in contrast to BPA, BPS does not appear to induce the metabolic syndrome that may lead to non-alcoholic fatty liver disease (NAFLD), in vitro. Although we have to pay special attention to BPS, its use could be less dangerous concerning this toxicological endpoint for human health.
This study is an overview that collects and analyzes many papers dealing with the effects of phthalates in humans and animals. They observe this at all ages and try to determine if there is a serious health risk. mehr
An very large proportion of the literature on the endocrine disruptors categorized as anti-androgens deals with phthalates, which are produced in large amounts for use as plastic emollients and additives. In this review, we bring together and analyse work on the effects of phthalates in animals and humans at different stages of their development to assess whether or not their possible anti-androgenic properties represent a significant threat to human health.
The database PubMed was systematically searched for all English language articles until July 2013 in each subject area discussed.
We provide an up-to-date exhaustive, comparative and critical assessment of both in vivo and in vitro studies undertaken to explore the effects of phthalates on the human testis from fetal life to adulthood. These results are compared and discussed in the light of the key data reported in the literature for mice and rats.
The current literature highlights the fact that
there is a huge difference between the number of studies performed in animals and in humans, with many fewer for humans;
there are differences in the way rats, mice, primates and humans respond to phthalates, for reasons that need to be further explored;
more work is required to clarify the contradictions, in the few existing human epidemiological studies at all stages of development, which may be partly explained by varying methods of exposure assessment;
in accordance with recent findings in rodents, it cannot be excluded that transgenerational effects of phthalates and/or epigenetic changes exist in humans;
a number of methodological limitations need to be solved for the in vitro and xenografting models using human fetal testis to fulfil their 'missing link' role between epidemiological studies in humans and rodent models; and
epidemiological and in vitro studies generally converge sufficiently to conclude that phthalate anti-androgenicity is plausible in adult men.
There is increasing evidence that bisphenol-A adversely affects humans. This text gives an overview of several studies dealing with the substance and its effects in animals and humans. mehr
There is growing evidence that bisphenol A (BPA) may adversely affect humans. 5BPA6 is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between 5BPA6 and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking 5BPA6 to human health; 53 published within the last year.
This review outlines this body of literature, showing associations between 5BPA6 exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental 5BPA6 exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental 5BPA6 exposure can be harmful to humans, especially in regards to behavioral and other effects in children.
DEHP (di (ethylhexyl) phthalate) has been implicated in damage to DNA. This study deals with this substance and thus wants to contribute to the education about this. mehr
Di(ethylhexyl) phthalate (DEHP) is a manufactured chemical commonly added to plastics: it is a ubiquitous environmental contaminant to which humans are exposed through multiple routes. DEHP is a rodent carcinogen with an extensive data base on genotoxicity and related effects spanning several decades. Although DEHP has been reported to be negative in most non-mammalian in vitro mutation assays, most studies were performed under conditions of concurrent cytotoxicity, precipitation, or irrelevant metabolic activation. However, a number of in vitro rodent tissue assays have reported DEHP to be positive for effects on chromosomes, spindle, and mitosis. A robust database shows that DEHP increases transformation and inhibits apoptosis in Syrian hamster embryo cells.
In a transgenic mouse assay, in vivo DEHP exposure increased the mutation frequency only in the liver, which is the target organ for cancer. In vitro exposure of human cells or tissues to DEHP induced DNA damage; altered mitotic rate, apoptosis, and cell proliferation; increased proliferation, tumor mobility, and invasiveness of tumor cell lines; and activated a number of nuclear receptors. DEHP has been shown to be an agonist for CAR2, a novel constitutive androstane receptor occurring only in humans. Environmental exposures of humans to DEHP have been associated with DNA damage. After taking into account study context and relevant issues affecting interpretation, in vitro studies reported that a similar DEHP concentration range induced both mutagenic and non-mutagenic effects in human tissues and, using a much more limited rodent database, transformation of embryonic rodent tissues. The human and rodent data suggest that DEHP induces cancer through multiple molecular signals, including DNA damage.
The analyses presented here may provide guidance for similar data sets used in structure–activity relationships, computational-toxicology extrapolations, and attempts to extrapolate in vitro results to predict in vivo effects for hazard characterization.
This article attempts to give an overview of the different health effects of bisphenol A previously discovered. mehr
Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. This compound is a building block of polycarbonate plastics often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and beverage containers. Studies have shown that BPA can leach from these and other products in contact with food and drink, and as a result, routine ingestion of BPA is presumed. This compound is also found in an enormous number of other products that we come into contact with daily, and therefore it is not surprising that it has been detected in the majority of individuals examined.
BPA is a known endocrine disruptor. Although initially considered to be a weak environmental estrogen, more recent studies have demonstrated that BPA may be similar in potency to estradiol in stimulating some cellular responses. Moreover, emerging evidence suggests that BPA may influence multiple endocrine-related pathways. Studies in rodents have identified adverse effects of BPA at levels at or below the current acceptable daily intake level for this compound. The various reported adverse effects of BPA are reviewed, and potential mechanisms of BPA action are discussed. Much more investigation is needed to understand the potential adverse health effects of BPA exposure in humans and to understand the multiple pathways through which it may act. Although many questions remain to be answered, it is becoming increasingly apparent that exposure to BPA is ubiquitous and that the effects of this endocrine disruptor are complex and wide-ranging.
This study presents the results of a large pregnancy study. It considers phthalate exposure in all age ranges (prenatal to full age). mehr
After briefly discussing human exposure to phthalates—diesters of 1,2-benzenedicarboxylic acid (phthalic acid)—this article first presents recent findings from the Study for Future Families, a multi-center pregnancy study in which the human analogue of the phthalate syndrome was first identified. This is one of an increasing number of studies that have investigated human endpoints in relation to environmental exposure to these ubiquitous compounds.
This literature, which includes a range of human health endpoints following prenatal, neonatal, childhood, and adult exposures, is then summarized. At least one significant association has been reported for urinary metabolites of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BzBP), diethyl phthlate (DEP), and di-isononyl phthalate (DINP) and for three of the urinary metabolites of di(2-ethylhexyl) phthalate (DEHP). Many of the findings reported in humans—most of which have been in males—are consistent with the anti-androgenic action that has been demonstrated for several phthalates. Replication of the results described here and further mechanistic studies are needed to strengthen links between phthalates and adverse health outcomes.
In this study, the association and influence of phthalates on obesity and insulin resistance was investigated. mehr
Phthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human males has been associated with increased prevalence of obesity, insulin resistance, and diabetes.
Our objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance.
Subjects were adult U.S. male participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002. We modeled six phthalate metabolites with prevalent exposure and known or suspected antiandrogenic activity as predictors of waist circumference and log-transformed homeostatic model assessment (HOMA; a measure of insulin resistance) using multiple linear regression, adjusted for age, race/ethnicity, fat and total calorie consumption, physical activity level, serum cotinine, and urine creatinine (model 1); and adjusted for model 1 covariates plus measures of renal and hepatic function (model 2). Metabolites were mono-butyl phthalates (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl)-hexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP).
In model 1, four metabolites were associated with increased waist circumference (MBzP, MEHHP, MEOHP, and MEP; p-values </= 0.013) and three with increased HOMA (MBP, MBzP, and MEP; p-values </= 0.011). When we also adjusted for renal and hepatic function, parameter estimates declined but all significant results remained so except HOMA-MBP.
In this national cross-section of U.S. men, concentrations of several prevalent phthalate metabolites showed statistically significant correlations with abdominal obesity and insulin resistance. If confirmed by longitudinal studies, our findings would suggest that exposure to these phthalates may contribute to the population burden of obesity, insulin resistance, and related clinical disorders.
This study addresses the occurrence and effects of bisphenol A in the living organism. It deals with how exactly this substance works in the body and what can arise from it. mehr
Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, in dental sealants, and in blends with other types of plastic products. The ester bond linking BPA molecules in polycarbonate and resins undergoes hydrolysis, resulting in the release of free BPA into food, beverages, and the environment, and numerous monitoring studies now show almost ubiquitous human exposure to biologically active levels of this chemical.
BPA exerts estrogenic effects through the classical nuclear estrogen receptors, and BPA acts as a selective estrogen receptor modulator. However, BPA also initiates rapid responses via estrogen receptors presumably associated with the plasma membrane. Similar to estradiol, BPA causes changes in some cell functions at concentrations between 1 pM and 1 nM, and the mean and median range of unconjugated BPA measured by multiple techniques in human pregnant maternal, fetal, and adult blood and other tissues exceeds these levels. In contrast to these published findings, BPA manufacturers persist in describing BPA as a weak estrogen and insist there is little concern with human exposure levels. Our concern with human exposure to BPA derives from:
In this study, the concentration of two human phthalates in urine was determined. This should help in the future determination of health risks from phthalate exposure. mehr
A number of phthalates and their metabolites are suspected of having teratogenic and endocrine disrupting effects. Especially the developmental and reproductive effects of di(2-ethylhexyl)phthalate (DEHP) are under scrutiny. In this study we determined the concentrations of the secondary, chain oxidized monoester metabolites of DEHP, mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) in urine samples from the general population. The utilization of the secondary metabolites minimized any risk of contamination by the ubiquitously present phthalate parent compounds. Included in the method were also the simple monoester metabolites of DEHP, dioctylphthalate (DOP), di-n-butylphthalate (DnBuP), butylbenzylphthalate (BBzP) and diethylphthalate (DEP).
Automated sample preparation was performed applying a column switching liquid chromatography system enabling online extraction of the urine on a restricted access material (RAM) and separation on a reversed phase analytical column. Detection was performed by negative ESI–tandem mass spectrometry in multiple reaction monitoring mode and quantification by isotope dilution. The excretion of 5DEHP6 and the other phthalates was studied by analyzing first morning urine samples from 53 women and 32 men aged 7–64 years (median: 34.2 years) living in northern Bavaria (Germany) who were not occupationally exposed to phthalates. Phthalate metabolites, secondary and primary ones, were detected in all specimens. Concentrations were found to vary strongly from phthalate to phthalate and subject to subject with differences spanning more than three orders of magnitude.
Median concentrations for excretion of 5DEHP6 metabolites were 46.8 μg/L for 5OH-MEHP (range 0.5–818 μg/L), 36.5 μg/L for 5oxo-MEHP (range 0.5–544 μg/L), and 10.3 μg/L for 5MEHP6 (range:<0.5 (limit of quantification, LOQ) to 177 μg/L). A strong correlation was found between the excretion of 5OH-MEHP and 5oxo-MEHP with a correlation coefficient of r=0.991, indicating close metabolic proximity of those two parameters but also the absence of any contaminating interference. Median concentrations for the other monoester metabolites were for mono-n-butylphthalate (MnBuP) 181 μg/L, for monobenzylphthalate (MBzP) 21.0 μg/L, for monoethylphthalate (MEP) 90.2 μg/L and for mono-n-octylphthalate (MOP)<1.0 μg/L (LOQ). These results will help to perform health risk assessments for the phthalate exposure of the general population.
The estrogenic effect of bisphenol A has already been demonstrated in human cells. This study presents a new method for the analysis of bisphenol A and its compounds in human urine. mehr
The estrogenic effects of bisphenol A (BPA) have been reported in human cells (E-screen assays) and in in vivo studies of rodents, although the latter reports remain controversial, as do the exposure levels and adverse health effects of BPA in humans. In this study we report on an analytical high-performance liquid chromatography/fluorescence method for BPA and its conjugate in human urine and on the application of this method in two student cohorts. Urine, along with information on smoking, alcohol intake, and coffee/tea consumption, was collected in two different years from two different groups of university students, 50 in 1992 and 56 in 1999.
Overall, the urinary BPA levels in the students in 1992 were significantly higher than were those in 1999. The BPA levelswere also positively correlated with coffee and tea consumption in the 1992 cohort but not in the 1999 cohort. We speculate that recent changes made in Japan regarding the interior coating of cans used to package these beverages may partly explain these findings. Key words: biologic monitoring, bisphenol A, can coatings, canned food, environmental exposure, glucuronide, HPLC, human, lifestyle, urine.
This study examined the monoester metabolism of seven commonly used phthalates using urine. mehr
Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate.
Women of reproductive age (20-40 years) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. Our findings strongly suggest that health-risk assessments for phthalate exposure in humans should include diethyl, dibutyl, and benzyl butyl phthalates.
Phthalates are found in many ordinary products. This study examines whether these substances have an impact on DNA integrity in human semen. mehr
Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity.
The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm.
The effect of estrogens and steroids on the central nervous system around the time of birth determines sexual differentiation. Bisphenol A may change socio-sexual behavior when in contact with the central nervous system. mehr
Perinatal action of estrogens or aromatizable steroids at the central nervous system level is responsible for brain sexual differentiation. Through early contact with the central nervous system, the estrogenic compound bisphenol A (BPA) could alter the processes affecting sociosexual behavior. To test this hypothesis, we studied agonistic and sexual behavior of adult female and male rats whose mothers were administered BPA (40 microg/kg/day) during pregnancy or lactation.
An intruder test revealed in males but not in females an increase in defensive behavior due to BPA. We studied the effect of BPA on sexual behavior by testing sexual orientation and sexual activity. Male sexual orientation toward a stimulus female was not affected by BPA, whereas the sexual activity test revealed a slight impairment of sexual performance due to BPA in terms of latency and frequency of intromissions. In females, BPA produced a small increase in sexual motivation and receptive behavior. In conclusion, BPA administration, both during pregnancy and during lactation, does not masculinize female behavior or potentiate masculinization processes of males. On the contrary, we observed a potentiation of female behavior in females and a depotentiation of male behavior in males.
In this study, it was found that bisphenol A reduces sperm production and testis weight even in small quantities in adult male rats. mehr
Bisphenol-A (BPA), a xenobiotic estrogenic compound widely used as a plastics monomer, has been suspected to have a so-called low dose effect on the reproductive system when administered transplacentally. In the present study, we investigated possible low-dose effects of BPA on spermatogenesis in adult rats. Male rats (13 weeks old; W13) were administrated a daily oral dose of BPA, ranging from 2 ng to 200 mg/kg, for 6 days and examined for testicular weight (TW) and daily sperm production (DSP) at W14 and W18.
A BPA dose as low as 20μg/kg tended to decrease TW and significantly reduced both DSP and the efficiency of spermatogenesis (DSP per gram testis) at W18, showing that BPA suppressed a normal increase in DSP and TW from W13 to W18. A single administration of 20 μg BPA/kg to W13 rats affected the intensity or mobility of several protein spots in the testicular cytosol fraction as shown by two-dimensional gel electrophoresis analysis. The present study showed that BPA at a low dose affects spermatogenesis in the adult rat.
This study investigated the effect of di-n-butyl phthalate (DBP) on rat reproductive ability. In the first branch generation the fertility had dropped sharply. mehr
The National Toxicology Program (NTP) conducted a continuous breeding study in SD rats with di-n-butyl phthalate (DBP) given via the diet at dose levels of up to 650 mg/kg/day. In the parental generation effects on reproduction were modest (small decreases in litter size and pup weight following treatment). However, the F(1) male offspring had marked decreases in fertility (at 650 mg/kg/day), with reduced sperm counts and reproductive tract malformations on reaching adulthood.
A no-observed-adverse-effect level (NOAEL) was not established for the study [lowest-observed-adverse-effect level (LOAEL) 66 mg/kg/day].In a study conducted at CIIT, the majority of these adverse changes could be reproduced over a similar dose range, but with a much shorter dosing regimen covering a critical window of development (gestation days 12-20). A default risk assessment for DBP indicates a reference dose (RfD) of 66 microg/kg/day, based on a LOAEL of 66 mg/kg/day and default factors of 10 for inter-species and inter-individual differences and the lack of a NOAEL.
Human exposure data would indicate worst-case scenarios to infants (via formula) in the dose range of the RfD. A default risk assessment appears to be inappropriate since rodents, unlike primates, metabolize phthalate diesters (including DBP) to monoesters extensively in the gut following oral administration. It is believed that the monoester is the active principle for induction of reproductive and developmental toxicity of specific phthalate esters. Thus, if humans produce very low levels of the monoester from an environmental exposure to the diester, the likelihood of any reproductive or developmental toxicity via the oral route appears extremely remote.
This study shows the results of a measurement of phthalates in 14-80 year old Germans. The burden of this substance is through the consumption of food. mehr
In the study presented here, we evaluated the exposure of the German population aged 14–80 years to bis(2-ethylhexyl)phthalate (DEHP) from consumption of food by means of deterministic and probabilistic estimations. The study was performed on the basis of an extensive review of literature from around the world reporting measured data on 5DEHP6 in food, as well as official German food control data. Only data from individual measurements were considered and used for fitting of distributions. A wide range of concentrations in non-representative samples are reported in the literature. On the basis of the available 5DEHP6 concentration data, 37 food categories were characterized which covered all major food classes. Food consumption data were taken from the diet history interviews of the German National Nutrition Survey 5II6 (Nationale Verzehrsstudie II) which was performed in 2005/2006 in a representative study population of 15,371 and is the most recent data source of this kind in Germany.
Average 5DEHP6 intake was estimated deterministically using data on measured concentrations in food (medians and means) and food consumption (means). A total dietary exposure to 5DEHP6 of 3.6 (median based) and 9.3 μg/kg of 5BW6 per day (based on mean values) was estimated deterministically. In addition, distributions of both concentrations and consumption figures were fitted using the @RISK best fit tool for further probabilistic estimations. This approach resulted in estimates within the same range: the estimated median 5DEHP6 intake in the whole population (both non-consumers and consumers of the foods considered) was 10.2, the arithmetic mean 14.0 and the 95th percentile 28.6 μg/kg of 5BW6 per day. The respective estimates for consumers only were 12.4, 18.7 and 36.5 μg/kg of 5BW6 per day. These results demonstrate that the probabilistic approach is able to estimate broader ranges of exposure even when using data representing an average intake. Moreover, it reflects the uncertainties of the estimation due to insufficient analytical data on concentrations of 5DEHP6 in food.
Dibutyl phthalate (DBP) is mainly absorbed through food. This study deals with the distribution and accumulation of this substance in the living organism. mehr
Dibutyl phthalate (DBP) is mainly taken up by the general population from food intake. To estimate intake of phthalates, determining distribution and accumulation of DBP in biological materials was a critical need. In this work, we set up two novel approaches with a monoclonal antibody specific to DBP to determine the distribution and accumulation of DBP in vivo. The contents of DBP in liver, kidney, stomach and testes were detected by immunofluorescence assays and indirect competitive ELISA. This data give directly evidence that indicates the distribution and accumulation of DBP in vivo.
Double-label immunofluorescence assay provides with a visual approach to determination of the distribution and accumulation of DBP. It indicated that DBP accumulated in subcutaneous tissue such as sweat gland, hair follicle. Both of immunofluorescence assay and ELISA can be used to detect the content of DBP in biological materials. Our assays showed that DBP accumulated in viscera being rich in fat, such as liver, kidney and could overcome physiological barriers to penetrate testes. The date suggested that the accumulations of DBP exposed through dermal route were less than that of oral route and most of DBP was metabolized in 2 or 3 days.
Various endocrine disruptors contained in plastic packaging and therefore in food were further investigated in this study. They represent a high health risk. mehr
The migration of plastic components or additives from packaging to food can produce a risk for human health, in fact many of these plasticizers and additives are “Endocrine Distruptors”, such as phthalates (PAEs), alkylphenols (APs), 2,2-bis(4-hydroxyphenyl)propane (bisphenol A or BPA) and di(2-ethylhexyl)adipate (DEHA). The evaluation of some PAEs, some APs, 5BPA6 and 5DEHA6 levels in common food packaging (oil and natural tuna cans, marmalade cap, yogurt packaging, polystyrene dish, teat, bread bag, film, baby’s bottle, aseptic plastic laminate paperboard carton and plastic wine top) was carried out by migration tests.
Furthermore to evaluate the potential migration of plasticizers and additives from plastic wine tops, two extraction methods were used, one through incubation at 40 °C for 10 days and one by ultrasounds extraction. The simulants employed were distilled water, acetic acid at 3%, ethanol at 15% for wine top. The food simulant was extracted by solid phase extraction (SPE) and analyzed by GC–MS. Comparing these results with 5EU6 restrictions all samples showed contaminant migration lower than 5SML6 and 5OML6 established. Finally, about the comparison of two extraction methods, the extraction carried out for 10 days at 40 °C may be better than the other one in order to detect all compounds.
The molecular size of phthalates determines how they can be used in products. This study presents results on studies of these substances in foods. mehr
Phthalates are a group of diesters of ortho-phthalic acid (dialkyl or alkyl aryl esters of 1,2-benzenedicarboxylic acid). Higher-molecular-weight phthalates, such as di-2-ethylhexyl phthalate (DEHP), are primarily used as plasticizers to soften polyvinyl chloride (PVC) products, while the lower-molecular-weight phthalates, such as diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBzP), are widely used as solvents to hold color and scent in various consumer and personal care products. Phthalates have become ubiquitous environmental contaminants due to volatilization and leaching from their widespread applications, and thus contamination of the environment has become another important source for phthalates in foods in addition to migration from packaging materials.
Human exposure to phthalates has been an increased concern due to the findings from toxicology studies in animals. DEHP, one of the important and widely used phthalates, is a rodent liver carcinogen. DEHP, DBP, BBzP, and several phthalate metabolites, such as monobutyl phthalate, monobenzyl phthalate, and mono-(2-ethylhexyl) phthalate, are teratogenic in animals. Since foods are the major source of exposure to phthalates, information on levels of phthalates in foods is important for human exposure assessment. The objective of this review is to identify the knowledge gaps for future investigations by reviewing levels of a wide range of phthalates in a variety of foods, such as bottled water, soft drinks, infant formula, human milk, total diet foods, and others, migration of phthalates from various food-packaging materials, and traditional and new methodologies for the determination of phthalates in foods.
The entry of pollutants in food via the packaging material has already been shown in several studies. This article provides an overview of legal controls, analytical methods and influencing factors. mehr
Packaging has become an indispensible element in the food manufacturing process, and different types of additives, such as antioxidants, stabilizers, lubricants, anti-static and anti-blocking agents, have also been developed to improve the performance of polymeric packaging materials. Recently the packaging has been found to represent a source of contamination itself through the migration of substances from the packaging into food. Various analytical methods have been developed to analyze the migrants in the foodstuff, and migration evaluation procedures based on theoretical prediction of migration from plastic food contact material were also introduced recently. In this paper, the regulatory control, analytical methodology, factors affecting the migration and migration evaluation are reviewed.
This study examines the extent to which bisphenol S, which has already been found in body fluids, can play a role in the physiological metabolism and thus potentially pose a threat to health. mehr
The interaction of bisphenol-S (BPS) with serum albumins using steady-state, synchronous, time-resolved, and circular dichroism spectroscopies has been investigated. The binding interactions have also been investigated in the case of bisphenol A (BPA). The fluorescence quenching pathways are different for both of these endocrine disrupting compounds. Steady-state and time-resolved studies reveal static quenching at lower concentrations of BPS and dynamic quenching at higher concentrations.
CD results also maintained the concentration dependent variation with a complete distortion of α-helices at 10–5 M BPS. Besides this, addition of sodium dodecyl sulfate (SDS) results in the further unfolding of protein in the case of BPS, whereas time-resolved studies indicated refolding for BPA denatured human serum albumin (HSA). The entire study indicates an irreversible binding of BPS with HSA. Hence, these results reveal the possible involvement of BPS in the physiological pathway raising a health threat as already their presences in body fluids are known.
Bisphenol A is used in large quantities in synthetic polymers and other substances. This study presents the sources, occurrence and results of various experiments of bisphenol A. mehr
Bisphenol A (BPA) is a chemical compound used in massive amounts in the production of synthetic polymers and thermal paper. In this review, the sources of BPA, which influence its occurrence in the environment and human surrounding will be presented. Data concerning BPA occurrence in food, water and indoor environments as well as its appearance in tissues and body fluids of human body will be shown.
The results of in vitro and in vivo studies and the results of epidemiological surveys showing toxic, endocrine, mutagenic and cancerogenic action of BPA will also be discussed. Moreover, data suggesting that exposure of human to BPA may elevate risk of obesity, diabetes and coronary heart diseases will be presented. Finally, biotransformation of BPA in animals, plants and microorganisms (bacteria, fungi, algae), resulting in the formation of various metabolites that exhibit different from BPA toxicity will be described.
This text gives an overview of the environmental effects and burdens of bisphenol A. mehr
Bisphenol A (CAS 85-05-7) may be released into the environment through its use and handling, and permitted discharges. BPA is moderately soluble (I20 to 300 mg/L at pH 7), may adsorb to sediment (Koc 314 to 1524), has low volatility, and is not persistent based on its rapid biodegradation in acclimated wastewater treatment plants and receiving waters (half-lives 2.5 to 4 days). BPA is “slightly to moderately” toxic (algal EC50 of 1000 μg/L) and has low potential for bioaccumulation in aquatic organisms (BCFs 5 to 68). The chronic NOEC for Daphnia magna is >3146 pg/L. Surface water concentrations are at least one to several orders of magnitude lower than chronic effects, with most levels nondetected.
Polycarbonate pistons used in experiments release estrogen substances. This could have already been influenced by a number of attempts by estrogen. mehr
In studies to determine whether Saccharomyces cerevisiae produced estrogens, the organism was grown in culture media prepared using distilled water autoclaved in polycarbonate flasks. The yeast-conditioned media showed the presence of a substance that competed with [3H]estradiol for binding to estrogen receptors (ER) from rat uterus. However, it soon became clear that the estrogenic substance in the conditioned media was not a product of the yeast grown in culture, but was leached out of the polycarbonate flasks during the autoclaving procedure. [3H]Estradiol displacement activity was monitored by ER RRA, and the active substance was purified from autoclaved medium using a series of HPLC steps. The final purified product was identified as bisphenol-A (BPA) by nuclear magnetic resonance spectroscopy and mass spectrometry.
BPA could also be identified in distilled water autoclaved in polycarbonate flasks without the requirement of either the organism or the constituents of the culture medium. Authentic BPA was active in competitive RRAs, demonstrating an affinity approximately 1:2000 that of estradiol for ER. In functional assays, BPA (10-25 nM) induced progesterone receptors in cultured human mammary cancer cells (MCF-7) at a potency of approximately 1:5000 compared to that of estradiol. The BPA effect on PR induction was blocked by tamoxifen. In addition, BPA (25 nM) increased the rate of proliferation of MCF-7 cells assessed by [3H]thymidine incorporation. Thus, BPA exhibited estrogenic activity by both RRA and two functional bioresponse assays.
Finally, MCF-7 cells grown in media prepared with water autoclaved in polycarbonate exhibited higher progesterone receptor levels than cells grown in media prepared with water autoclaved in glass, suggesting an estrogenic effect of the water autoclaved in polycarbonate. Our findings raise the possibility that unsuspected estrogenic activity in the form of BPA may have an impact on experiments employing media autoclaved in polycarbonate flasks. It remains to be determined whether BPA derived from consumer products manufactured from polycarbonate could significantly contribute to the pool of estrogenic substances in the environment.