Abstract  The concentrations of six priority phthalic acid esters (PAEs) in intensively managed suburban vegetable soils in Nanjing, east China, were analyzed using gas chromatography-mass spectrometry (GC-MS). The total PAE concentrations in the soils ranged widely from 0.15 to 9.68 mg kg(-1) with a median value of 1.70 mg kg(-1), and di-n-butyl phthalate (DnBP), bis-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP) were the most abundant phthalate esters. Soil PAE concentrations depended on the mode of use of plastic film in which PAEs were incorporated as plasticizing agents and both the plastic film and poultry manure appeared to be important sources of soil PAEs. Vegetables in rotation with flooded rice led to lower concentrations of PAEs in soil. The results indicate that agricultural plastic film can be an important source of soil PAE contamination and further research is required to fully elucidate the mechanisms of PAE contamination of intensive agricultural soils with different use modes of use of plastic film.

Abstract  Phthalate esters (PAEs), a group of emerging organic contaminants, have become a serious issue arousing much attention for their ubiquitous presence and hazardous impact on the environment. This study provides the first data on distribution of PAEs in the sediments in the Qiantang River, Zhejiang Province, China, and the inference with urbanization and river flow regime. PAEs were detected in all 23 sediment samples analyzed, and the total concentrations of their 16 congeners in sediments ranged from 0.59 to 6.74μg/g dry weight (dw), with the geometric mean value of 2.03μg/g dw. Of the 16 PAE congeners, di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and di(2-ethylhexyl) phthalate (DEHP) were present in all sediment samples. The PAEs concentrations in urban regions were higher than those in rural regions because of higher discharge of PAEs from plastic materials in urbanized areas. Concentrations of PAEs were positively correlated with sediment organic matter (fOM) and negatively correlated with logistic value of annual average flow volume at sample sites. River flow regime modified by man-made dams significantly affected the distribution of PAEs. Analysis of congener composition of PAEs indicated that the DEHP was predominant congener in the Qiantang River. The normalized concentration of DEHP exceeded recommended environmental risk limit (ERL).

Abstract  Dibutyl phthalate (DBP), a widely used phthalate, is known to cause many serious diseases, especially in the reproductive system. However, little is known about the effects of its metabolite, mono-n-butyl phthalate (MBP), on preimplantation embryo development. In the present study, we found that treatment of embryos with 10⁻³ M MBP impaired developmental competency, whereas exposure to 10⁻⁴ M MBP delayed the progression of preimplantation embryos to the blastocyst stage. Furthermore, reactive oxygen species (ROS) levels in embryos were significantly increased following treatment with 10⁻³ M MBP. In addition, 10⁻³ M MBP increased apoptosis via the release of cytochrome c, whereas immunofluorescent analysis revealed that exposure of preimplantation embryos to MBP concentration-dependently (10⁻⁵, 10⁻⁴ and 10⁻³ M) decreased DNA methylation. Together, the results indicate a possible relationship between MBP exposure and developmental failure in preimplantation embryos.

Abstract  In this paper, using environmental hormone dibutyl phthalate (DBP) in the contaminated foods as the template molecule, methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate ester (EDMA) as cross linking agent, the molecularly imprinted polymer (MIP) was prepared on the silica surface. The MIP was characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimeric analysis (TGA) and automated surface area analyzer. The property of adsorption was tested using static adsorption method in water phrase. The results of FTIR indicate that there are recognition groups in the microspheres after imprinting. TGA illustrates the silica gel surface has been coated with a layer of polymer after the synthesis reaction. And the MIP can bear the high temperature of 200 degrees C. The thickness of the imprinted polymer coated on silica gel surface is estimated via the pore size data is about 1.5nm. The result of static adsorption experiment shows that the saturated adsorption capacity of the MIP was 8.940mg/g.

Abstract  PURPOSE OF REVIEW: Phthalates are multifunctional chemicals used in personal care products, medications, and plastics. We reviewed the epidemiological literature examining the relationship between early life phthalate exposure and pediatric health outcomes.

RECENT FINDINGS: Five studies from Asia, Europe, and the United States suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-butyl phthalate (DBP), and di-ethyl phthalate (DEP) exposures are associated with alterations in infant/toddler physical development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure.

SUMMARY: Several epidemiological studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. Although anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes.

Abstract  Phthalate diesters, widely used in flexible plastics and consumer products, have become prevalent contaminants in the environment. Human exposure is ubiquitous and higher phthalate metabolite concentrations documented in patients using medications with phthalate-containing slow release capsules raises concerns for potential health effects. Furthermore, animal studies suggest that phthalate exposure can modulate circulating hormone concentrations and thus may be able to adversely affect reproductive physiology and the development of estrogen sensitive target tissues. Therefore, we conducted a systematic review of the epidemiological and experimental animal literature examining the relationship between phthalate exposure and adverse female reproductive health outcomes. The epidemiological literature is sparse for most outcomes studied and plagued by small sample size, methodological weaknesses, and thus fails to support a conclusion of an adverse effect of phthalate exposure. Despite a paucity of experimental animal studies for several phthalates, we conclude that there is sufficient evidence to suggest that phthalates are reproductive toxicants. However, we note that the concentrations needed to induce adverse health effects are high compared to the concentrations measured in contemporary human biomonitoring studies. We propose that the current patchwork of studies, potential for additive effects and evidence of adverse effects of phthalate exposure in subsequent generations and at lower concentrations than in the parental generation support the need for further study.

Abstract  Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate (DBP; from gestational day (GD) 14.5 to postnatal day (PND) 6) or diethylstilbestrol (DES; from GD14.5 to GD16.5) during a short gestational/lactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.

Abstract  BACKGROUND: Phthalates are prevalent environmental exposure chemicals with rising concern on various health effects, including pulmonary function. Meanwhile, elderly people are more susceptible to environmental exposure, and their decreasing lung function is an important health issue.

OBJECTIVES: To investigate the association between urinary phthalate metabolite levels and indices for pulmonary function, and evaluate effect modification by genetic polymorphisms of oxidative-stress related genes, catalase (CAT), superoxide dismutase (SOD2), and myeloperoxidase (MPO) in elderly Koreans.

METHODS: We conducted a panel study on 418 individuals over 60 years old in Seoul, Korea, and repeatedly measured urinary phthalate metabolite levels and ran pulmonary function tests. Genetic polymorphisms of CAT (rs769218, rs769217), SOD2 (rs4880, rs2758331, rs5746136) and MPO (rs2071409, rs7208693) were determined. Mixed effect model was used to investigate association of phthalate levels with pulmonary function indices and to examine the effect of CAT, SOD2 and MPO polymorphisms on the association.

RESULTS: Inverse association was demonstrated between sum of mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate (∑DEHP) levels and FEV1/FVC (β=-0.632, p=0.0275) or FEF25-75 (β=-0.077, p=0.025) after adjusting for age, months after previous measurements, sex, body mass index, cotinine, mean temperature and dew point. The effect of ∑DEHP on lung function was significant only in subjects with certain genotypes, and having all significant genotypes in three genes showed significant difference in the phthalate-pulmonary function association (FEV1/FVC: β=-2.169, p=0.0032; FEF25-75: β=-0.155, p=0.0103), while other combinations showed less estimate size without any significance.

CONCLUSIONS: Urinary phthalate metabolites levels are associated with decreasing pulmonary function in elderly Koreans, and effect modification of certain CAT, SOD2 and MPO polymorphisms on the association is suggested.

Abstract  We conducted an epidemiologic study to test the hypothesis that women who smoke have reduced fertility. Data on smoking history and number of noncontracepting cycles until conception were collected from 678 pregnant women. Thirty-eight percent of nonsmokers conceived in their first cycle compared with 28% of smokers. Smokers were 3.4 times more likely to have taken greater than a year to conceive compared with nonsmokers. After adjusting for potential confounding variables by Cox proportional hazards regression, fertility of smokers was estimated to be 72% of the fertility of nonsmokers. Heavy smokers experienced lower fertility than did light smokers (57% and 75% of the pregnancy rate of nonsmokers, respectively). Fertility was not affected by the husband's smoking. These data provide evidence that reduced fertility should be added to the growing list of reproductive hazards of cigarette smoking.

Abstract  The ubiquitous use of phthalate esters in plastics, building material, medical devices, personal care products and food packaging materials results in a widespread exposure of general population. This study reports measurement of urinary concentration of phthalate metabolites in France and provides a first assessment of the exposure of French pregnant women to this chemical class. For the majority of the phthalate metabolites, concentrations measured in urine were similar to those reported in previous studies except for two phthalates that were characterized by high concentrations of metabolites if compared to previous European and American studies: DiNP (Di-iso-nonylphthalate) and DEHP (Di(2-ethylhexyl)phthalate). In a second part of the study, a pharmacokinetic model was used in order to gain understanding on exposure to DEHP. A high concentration of the primary metabolite of DEHP, MEHP (Mono(2-ethylhexyl)phthalate), was thus identified probably because of a very recent exposure to perfusion materials at the hospital. Pharmacokinetics modelling highlighted that gathering data on the time gap between exposure and biomonitoring is an essential information requirement for reconstructing the dose of non persistent pollutants. Information about exposure pathway is also crucial for conducting effective reverse dosimetry.

Abstract  Dibutyl-phthalate (DBP) is a ubiquitous environmental contaminant. However, its neurotoxic effects on neonatal, immature or mature brains remain unclear. Here, we aimed to investigate the neurotoxicity of perinatal exposure of DBP on rodent offspring animals. Pregnant rats received intragastric DBP (500mg/kg body weight) daily from gestational day (GD) 6 to postnatal day (PND) 21. Animals in the control group received the same volume of edible corn oil. Brain sections or tissues from offspring rats on PND5, PND21 and PND60 were collected for analysis. Histological examination demonstrated that perinatal exposure of DBP resulted in hippocampal neuron loss and structural alternation in neonatal and immature offspring rats (PND5 and PND21), while no significant change was found in mature rats (PND60). DBP exposure induced cell apoptosis in hippocampal neurons of these neonatal and immature animals, as evidenced by the increased number of TUNEL-positive and Annexin V-propidium iodide (PI) positive cells and up-regulated caspase-3 activity. Moreover, DBP exposure decreased the expression of synaptophysin in the hippocampus and reduced both the slope and amplitude of field excitatory postsynaptic potentials (fEPSPs). DBP also impaired the spatial learning and memory of offspring rats. However, no significant difference in the susceptibility to DBP-induced neurotoxicity was found between male and female offspring rats. Our findings indicated that perinatal exposure of DBP could induce neurotoxicity in neonatal and immature offspring animals, but had no influence on mature animals after DBP withdrawal. These results may provide basic experimental evidence for better understanding the neurotoxic effects of DBP on neonatal, immature and mature brains.

Abstract  OBJECTIVE: To investigate the effect of phthalates exposure from drinking water on children's intelligence and secretion of thyroid hormone.

METHODS: Two villages in S County were selected randomly as polluted area and control area according to the distance from the Shaying river basin. Phthalates including DEP, DBP, DMP, DEHP were measured both in the river water and drinking water using HPLC method. Children aged 8 to 13 years old studying in the village primary school were recruited by cluster sampling (n = 154). The combined Reven Test was used to test children intelligence and ELISA method was used to determined thyroid hormone levels.

RESULTS: The concentrations of phthalates (DEP, DBP) were exceeding standards of surface water quality in any of the three sections of the river. Compared to the control area, the concentration of DEP and DBP in drinking water were significant higher in the polluted area than that in control area (P < 0.05). Children from polluted area had significant higher FT4 concentration compared to children from control area (P < 0.05). Intelligence level in children from polluted area was lower than that from control area (P < 0.05).

CONCLUSION: The drinking water has been polluted by Shaying river and thyroid hormones levels of children were affected in the polluted areas. It is necessary to verify if this change is related to the phthalates.

Abstract  OBJECTIVE: To evaluate the association between the use of medications potentially containing phthalates and urinary concentrations of specific phthalate metabolites around conception.

METHODS: Women enrolled in the Environment and Reproductive Health project from 2006 to 2009 completed questionnaires about the use of medications and provided multiple urine samples before and after conception. We compared the mean urinary concentration of phthalate metabolites between users of phthalate containing medications and a matched unexposed control group.

RESULTS: One woman used Asacol(®) (mesalamine), which utilizes dibutyl phthalate (DBP) as a delayed release coating material, and had a mean urinary concentration of the main DBP metabolite 200 times higher than the controls (8176μg/L vs. 37.5μg/L). The three users of stool softeners had a higher concentration of the main diethyl phthalate (DEP) metabolite (8636μg/L vs. 714.2μg/L). Neither the three additional Prilosec(®) (omeprazole) users nor one cyclobenzaprine user had higher urinary concentration than controls.

CONCLUSION: Selected medications may be important sources of DBP and DEP exposures around conception.

Abstract  This review addresses whether there is a secular increasing trend in mate reproductive developmental disorders (cryptorchidism, hypospadias, testis cancer, low sperm counts), and highlights the limitations of available data and how these issues are being addressed. These disorders are considered to represent a syndrome of disorders [testicular dysgenesis syndrome (TDS)] with a common origin in fetal life, and in which "endocrine disruption" plays a central role. The potential involvement of environmental estrogens in the etiology of these disorders is reviewed in light of new understanding about the pathways and dose-effect relationships of estrogen action on male reproductive development. Several new pathways of estrogen action have been identified, including suppression of the production of testosterone and insulin-like factor-3 by fetal/neonatal Leydig cells and suppression of androgen receptor expression in androgen target tissues. It is tentatively concluded that identified environmental chemicals are unlikely to activate these pathways because of their intrinsically weak estrogenicity. However, chemicals that may alter endogenous estrogen production, bioavailability, or inactivation represent a new focus of concern. Additionally, environmental chemicals that alter endogenous levels of androgens in the rat fetus (certain phthalates) induce a similar collection of disorders to TDS. Whether human exposure to such compounds might contribute to TDS remains to be shown, but studies in animals should help to define susceptible pathways for induction of TDS.

Abstract  The original 'oestrogen hypothesis' postulated that the apparent increase in human male reproductive developmental disorders (testis cancer, cryptorchidism, hypospadias, low sperm counts) might have occurred because of increased oestrogen exposure of the human foetus/neonate; five potential routes of exposure were considered. This review revisits this hypothesis in the light of the data to have emerged since 1993. It addresses whether there is a secular increasing trend in the listed disorders and highlights the limitations of available data and how these are being addressed. It considers whether new data has emerged to support the suggestion that increased oestrogen exposure could cause these abnormalities and reviews new data on potential routes via which such increased exposure could have occurred. Secular trends: The disorders listed above are now considered to represent a syndrome of disorders (testicular dysgenesis syndrome, TDS) with a common origin in foetal life. Testicular cancer has increased in incidence in Caucasian men worldwide and lifetime risk is 0.3-0.8%. Secular trends in cryptorchidism are unclear but it is by far the commonest (2-4% at birth) congenital abnormality in either sex. Secular trends for hypospadias are not robust, although most studies suggest a progressive increase; registry data probably under-estimates incidence, but based on this data hypospadias is the second most common (0.3-0.7% at birth) congenital malformation. Retrospective analyses of sperm count data show a global downward trend but this is inconclusive - prospective studies using standardized methodology show significant differences between countries and very low sperm counts in the youngest cohort of men. For all disorders, other then testis cancer, standardized prospective studies are the best way forward and are in progress across Europe. Oestrogen effects: Evidence that foetal exposure to oestrogens can induce the above disorders has strengthened. New pathways via which such changes could be induced have been identified, including suppression of testosterone production by the foetal testis, suppression of androgen receptor expression and suppression of insulin-like factor-3 (InsL3) production by foetal Leydig cells. Other evidence suggests that the balance between androgen and oestrogen action may be important in induction of reproductive tract abnormalities. Oestrogen exposure: Although many new environmental oestrogens have been identified, their uniformly weak oestrogenicity excludes the possibility that they could induce the above disorders. However, emerging data implicates various environmental chemicals in being able to alter endogenous levels of androgens (certain phthalates) and oestrogens (polychlorinated biphenyls, polyhalogenated hydrocarbons), and the former have been shown to induce a similar collection of disorders to TDS. Other mechanisms via which increased fetal exposure to pregnancy oestrogens might occur (increasing trend in obesity, dietary changes) are also discussed.

Abstract  To investigate the levels and possible determinants of phthalate esters (PEs) in settled house dust from urban dwellings with young children, dust was collected from 215 urban houses in Nanjing, China, and 145 outdoor settled dust samples were collected nearby. Six PEs were measured by gas chromatography/mass spectrometry. All PEs were detected in the dust from approximately 90% of the houses, with the exception of dioctyl phthalate (DOP), which had only a 59% detection rate. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) were the most abundant PEs, with geometric means of 110 and 16.4 mu g g(-1), respectively, and maximal concentrations 9950 and 2150 mu g g(-1). Factor analysis showed that DBP, DEHP and benzyl butyl phthalate (BBP) might come from the same source and were significantly influenced by the use of solid-wood floor wax. High BBP, DEHP, DOP and total PE levels were associated with indices of dampness, and high DOP was associated with humidifier use. In conclusion, six PEs are ubiquitous in urban settled house dust in Nanjing, China, and both plastic materials and cosmetic and personal care products are important sources. Flooring material, dampness and humidifier use potentially influence house dust PE levels.

Abstract  Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to reduce flammability, increase plasticity, or improve solubility of other substances. Many of these compounds, which are components of plastic, the new generation of cosmetics, medical devices, food packaging and other everyday products, are easily released into the environment. Many studies have shown that a major lipophilicity characterizes substances such as phthalates, BPA, TBBPA and PCBs. This feature allows them to easily penetrate into living cells, accumulate in the tissues and the organs, and affect human and animal health. Due to the chemical structures, these compounds are able to mimic some endogenous hormones such as estradiol and to disrupt the hormone homeostasis. They can also easily pass the placental barrier and the blood-brain barrier. As numerous studies have shown, these chemicals disturb the proper functions of the nervous system from the earliest moments of life. It has been proven that these compounds affect neurogenesis as well as the synaptic transmission process. As a consequence, they interfere with the formation of the sex of the brain, as well as with the learning processes, memory and behavior. Additionally, the cytotoxic and pro-apoptotic effect may cause neurodegenerative diseases. This article presents the current state of knowledge about the effects of phthalates, BPA, TBBPA, and PCBs on the nervous system.

Abstract  In the European Community, selected phthalate esters (PE) are restricted in their use for the manufacture of toys and childcare articles. As PE are mainly used as plasticizers for poly(vinyl chloride) (PVC), a high sensitivity analytical method was developed to determine the PE content in PVC toys by using ultra high performance liquid chromatography coupled with electronic spray mass spectrum (UPLCMS/MS). The LOD of the method is low to the level of ng/L. The method was verified by specificity, linearity, sensitivity, accuracy and precision. This research will provide a useful and convenient way to monitor the production of PVC toys. (C) 2013 Elsevier Ltd. All rights reserved.

Abstract  BACKGROUND: There is concern over potential neurobehavioral effects of prenatal phthalate exposures, but available data are inconsistent.

OBJECTIVES: To examine associations between prenatal urinary concentrations of phthalate metabolites and neurobehavioral scores among children.

METHODS: We measured phthalate metabolite concentrations in urine samples from 153 pregnant participants in the Study for Future Families, a multicenter cohort study. Mothers completed the Child Behavior Checklist when the children were 6-10 years of age. We estimated overall and sex-specific associations between phthalate concentrations and behavior using adjusted multiple regression interaction models.

RESULTS: In boys concentrations of mono-isobutyl phthalate were associated with higher scores for inattention (β = 0.27; 95% CI: 0.04, 0.50), rule-breaking behavior (β = 0.20; 95% CI: 0.01, 0.38), aggression (β = 0.34; 95% CI: 0.09, 0.59), and conduct problems (β = 0.39; 95% CI: 0.20, 0.58), while the molar sum of di-(2-ethylhexyl) phthalate metabolites was associated with higher scores for somatic problems (β = 0.15; 95% CI: 0.03, 0.28). Higher monobenzyl phthalate concentrations were associated with higher scores for oppositional behavior (β = 0.16; 95% CI: 0.01, 0.32) and conduct problems (β = 0.21; 95% CI: 0.06, 0.37) in boys, but with reduced anxiety scores in girls (β = -0.20; 95% CI: -0.39, -0.01). In general, the associations reported above were close to the null among girls. Model coefficients represent the difference in the square-root transformed outcome score associated with a 1-unit increase in log-transformed metabolites.

CONCLUSIONS: Our results suggest associations between exposure to certain phthalates in late pregnancy and behavioral problems in boys. Given the few studies on this topic and methodological and population differences among studies, additional research is warranted.

Abstract  A GC/MS method was developed for the identification and quantification of 14 phthalates: 8 phthalates classified H360 (DBP, DEHP, BBP, DMEP, DnPP, DiPP, DPP and DiBP), 3 phthalates proposed to be forbidden in medical devices (DnOP, DiNP and DiDP) and 3 other phthalates none regulated (DMP, DCHP and DEP) which may interfere with hormone function. In order to identify and quantify other plasticizers that are commonly used in PVC medical devices such as DEHP substitute, 5 non-phthalate plasticizers (ATBC, DEHA, DEHT, TOTM, and DINCH) were included in this study. Analyses are carried out on a GC/MS system with electron impact ionization mode (EI). The separation of plasticizers is obtained on a cross-linked 5%-phenyl/95%-dimethylpolysiloxane capillary column 30m×0.25mm (i.d.)×0.25μm film thickness using a gradient temperature. Compounds quantification is performed by external calibration using an internal standard. Validation elements on standard solutions were determined using the ISO 12787 standard approach. Plasticizers are extracted from PVC medical devices using THF for dissolving the PVC part of the sample followed by precipitation of the PVC by addition of ethanol. The supernatant is injected into a GC/MS system after dilution in ethanol. Different validation elements, including extraction recoveries for all compounds or for DEHP a cross-validation of the extraction process using the European pharmacopoeia monograph 3.1.14 as reference method, are discussed. Results obtained on 61 medical devices in PVC and 12 raw materials used as plasticizers are given.

Abstract  in their 10th or 11th years, while others who are equally healthy may not experience menarche until they 'are 14, 15, or even older. Menarche is, however, only a single event in the combination of physical changes which constitute puberty. The adolescent growth spurt, the development of the breasts, and the growth of the pubic hair occur more or less concurrently, and take, on the average, about 3 years from beginning to completion, with menarche occurring usually in the latter half of this period (Tanner, 1962). At present we lack detailed information about the rate at which girls progress through the stages of puberty and about the relation of one event to another. Only longitudinal studies (i.e. studies in which the same individuals are examined repeatedly over a period of time) can provide this information, which would be helpful both to the clinician in distinguishing the normal from the abnormal, and to the neuro-endocrinologist in constructing hypotheses about the mechanisms by which puberty is controlled. Present knowledge is based on studies carried out on small numbers of children in the United States a generation ago, together with some German studies of a similar period (for literature see Tanner, 1962).

Abstract  The Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, September 2013 provides nationally representative biomonitoring data that has become available since the publication of the Fourth National Report on Human Exposure to Environmental Chemicals, 2009. The Updated Tables, September 2013 includes all the updates previously provided in Updated Tables, July 2010 through Updated Tables, March 2013. The Updated Tables, September 2013 present data for 91 chemicals measured in serum pooled samples that have not been reported in any previous Updated Tables. Since publication of the Fourth Report, 2009, 201 chemicals have updated tables and 49 chemicals have been added, for a total of 250 chemicals presented in these Updated Tables.