Association between prenatal exposure to phthalates and the health of newborns

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 MBP and amniotic fluid MBP (R(2)=0.156, p<0.05) in all infants and, only in female infants, a significantly negative correlation between amniotic fluid MBP, AGD (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.     

Obstetrical outcomes and biomarkers to assess exposure to phthalates: A review

Studies of the effects on pregnancy outcomes of in utero exposure to phthalates, contaminants that are widely present in the environment, have yielded conflicting results. In addition, the mode of assessment of exposure varies between studies. The aim of this review was therefore to establish a current state of knowledge of the phthalates and metabolites involved in unfavorable pregnancy outcomes. Extant data were analyzed to determine which biomarker is the best suited to assess the relation between in utero exposure to phthalates and pregnancy outcomes.This review of the literature was conducted using the database of PubMed. A search was made of studies investigating exposure to phthalates and the following birth outcomes: preterm birth (gestational age < 37 weeks), change in gestational age, change in body size at birth (birth weight, length, head circumference), anti-androgenic function, decreased anogenital distance, cryptorchidism, hypospadias and congenital malformation. The methodological approach adopted in each study was examined, in particular the methods used for exposure assessment (biomarkers and/or questionnaire).Thirty-five studies were included. Premature birth and decreased anogenital distance were the most commonly reported outcomes resulting from a moderate level of exposure to phthalates. The principal metabolites detected and involved were primary metabolites of di-2(ethylhexyl)-phthalate (DEHP) and di-n-butyl-phthalate (DnBP). No clear conclusion could be drawn with regard to gestational age at birth, body size at birth and congenital malformations. In epidemiological studies, maternal urine is the most suitable matrix to assess the association between in utero exposure to phthalates and pregnancy outcomes: in contrast to other matrices (cord blood, amniotic fluid, meconium and milk), sampling is easy, non-invasive and, can be repeated to assess exposure throughout pregnancy. Oxidative metabolites are the most relevant biomarkers since they are not prone to external contamination.Further epidemiological studies are required during pregnancy to i) determine the role of phthalates other than DEHP [currently replaced by various substitution products, in particular diisononyl-phthalate (DiNP)]; ii) establish the effect of phthalates on other outcomes (body size adjusted for gestational age, and congenital malformations); iii) determine the pathophysiological pathways; and iv) identify the most suitable time for biomarker determination of in utero exposure to phthalates.     

Assessing correlations between geological hazards and health outcomes: Addressing complexity in medical geology

BackgroundThe field of medical geology addresses the relationships between exposure to specific geological characteristics and the development of a range of health problems: for example, long-term exposure to arsenic in drinking water can result in the development of skin conditions and cancers. While these relationships are well characterised for some examples, in others there is a lack of understanding of the specific geological component(s) triggering disease onset, necessitating further research.ObjectivesThis paper aims to highlight several important complexities in geological exposures and the development of related diseases that can create difficulties in the linkage of exposure and health outcome data. Several suggested approaches to deal with these complexities are also suggested.DiscussionLong-term exposure and lengthy latent periods are common characteristics of many diseases related to geological hazards. In combination with long- or short-distance migrations over an individual's life, daily or weekly movement patterns and small-scale spatial heterogeneity in geological characteristics, it becomes problematic to appropriately assign exposure measurements to individuals. The inclusion of supplementary methods, such as questionnaires, movement diaries or Global Positioning System (GPS) trackers can support medical geology studies by providing evidence for the most appropriate exposure measurement locations.ConclusionsThe complex and lengthy exposure–response pathways involved, small-distance spatial heterogeneity in environmental components and a range of other issues mean that interdisciplinary approaches to medical geology studies are necessary to provide robust evidence.     

Applying radioecology in a world of multiple contaminants

This paper presents a review of the current status of radioecology and how it might be applied to contribute to a broader range of environmental pollution and contamination problems. In many respects radioecology is a unique and specialised branch of environmental science. However, radioecologists could be much more aware of the similarities and differences between their field and other fields of environmental pollution science. Areas of common interest described herein are exposure and risk assessment, and the problem of the bioavailability of potentially toxic substances in environmental media. It is concluded that radiometric methods and radioecological modelling methods can assist significantly with understanding and quantifying both these issues. The existence of multiple contaminants at many locations around the world dictates that assessment and remediation exercises should be carried out in an integrated fashion, as a partnership between scientific disciplines.     

Association of perfluoroalkyl substances exposure in utero with reproductive hormone levels in cord blood in the Hokkaido Study on Environment and Children's Health

BackgroundExposure to perfluoroalkyl substances (PFASs) may disrupt reproductive function in animals and humans. Although PFASs can cross the human placental barrier, few studies evaluated the effects of prenatal PFAS exposure on the fetus' reproductive hormones.ObjectiveTo explore the associations of prenatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) with cord blood reproductive hormones.MethodsIn the prospective birth cohort (Sapporo cohort of the Hokkaido study), we included 189 mother–infant pairs recruited in 2002–2005 with both prenatal maternal and cord blood samples. PFOS and PFOA levels in maternal blood after the second trimester were measured via liquid chromatography–tandem mass spectrometry. We also measured cord blood levels of the fetuses' reproductive hormones, including estradiol (E2), total testosterone (T), progesterone (P4), inhibin B, insulin-like factor 3, steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone, and prolactin (PRL).ResultsThe median PFOS and PFOA levels in maternal serum were 5.2 ng/mL and 1.4 ng/mL, respectively. In the fully adjusted linear regression analyses of the male infants, maternal PFOS levels were significantly associated with E2 and positively, and T/E2, P4, and inhibin B inversely; PFOA levels were positively associated with inhibin B levels. Among the female infants, there were significant inverse associations between PFOS levels and P4 and PRL levels, although there were no significant associations between PFOA levels and the female infants' reproductive hormone levels.ConclusionsThese results suggest that the fetal synthesis and secretion of reproductive hormones may be affected by in utero exposure to measurable levels of PFOS and PFOA.     

Behavioral alterations due to diesel exhaust exposure

Several experiments examining the effects of diesel exhaust on the behavior of rats are reported. Animals were exposed either as adults or neonates. The spontaneous locomotor activity (SLA), measured in standard running wheel cages, of adult rats exposed for 8 h/day, 7 days/week was significantly less than that of controls. Experiments involving diesel exhaust exposure to neonatal rats indicated that adult rats, exposed to diesel exhaust during their neonatal lives, were significantly less active as measured by SLA. Adult rats, exposed to 20 h diesel per day as neonates, were placed in skinner boxes after the SLA experiment described above had been completed. The exhaust exposed animals showed significantly decreased acquisition of a food reinforced bar pressing task. All animals that learned this task extinguished at the same rate. The results of the neonatal diesel exhaust experiments support the hypothesis that diesel exhaust exposure during development of an organism can lead to behavioral differences in adulthood.     

The precautionary principle and chemicals management: The example of perfluoroalkyl acids in groundwater

Already in the late 1990s microgram-per-liter levels of perfluorooctane sulfonate (PFOS) were measured in water samples from areas where fire-fighting foams were used or spilled. Despite these early warnings, the problems of groundwater, and thus drinking water, contaminated with perfluoroalkyl and polyfluoroalkyl substances (PFASs) including PFOS are only beginning to be addressed. It is clear that this PFAS contamination is poorly reversible and that the societal costs of clean-up will be high. This inability to reverse exposure in a reasonable timeframe is a major motivation for application of the precautionary principle in chemicals management. We conclude that exposure can be poorly reversible; 1) due to slow elimination kinetics in organisms, or 2) due to poorly reversible environmental contamination that leads to continuous exposure. In the second case, which is relevant for contaminated groundwater, the reversibility of exposure is not related to the magnitude of a chemical's bioaccumulation potential. We argue therefore that all PFASs entering groundwater, irrespective of their perfluoroalkyl chain length and bioaccumulation potential, will result in poorly reversible exposures and risks as well as further clean-up costs for society. To protect groundwater resources for future generations, society should consider a precautionary approach to chemicals management and prevent the use and release of highly persistent and mobile chemicals such as PFASs.     

Drugs of abuse in surface and tap waters of the Tagus River basin: Heterogeneous photo-Fenton process is effective in their degradation

This work investigates for the first time the occurrence of drugs of abuse and metabolites in surface waters from the Tagus River on its way through the province of Toledo (downstream Madrid metropolitan area) and in drinking waters in two nearby cities. Some of the studied drugs are used for therapeutic purposes but they can also be consumed as illicit drugs. The results of this preliminary study have revealed the presence of 12 out of 22 drugs of abuse analyzed in fluvial water at concentrations ranging from 1.14 to 40.9 ng/L. The largest concentrations corresponded to the anxiolytics diazepam and lorazepam, the cocaine metabolite benzoilecgonine, the amphetamine-like compound ephedrine, and the methadone metabolite EDDP. All these substances, except for lorazepam, were detected in all the sampling points. Traces of methadone and ephedrine were detected in some samples of tap water. Despite the low concentrations of these pollutants, effects on wildlife or human health cannot be disregarded, especially on vulnerable population. Thus, the treatment of these substances using a heterogeneous photo-Fenton process has been evaluated, rendering a remarkable effectiveness for their degradation.     

Levels of polybrominated diphenyl ethers (PBDEs) in breast milk from central Taiwan and their relation to infant birth outcome and maternal menstruation effects

In utero exposure to polybrominated diphenyl ethers (PBDEs) reduces the number of ovarian follicles in rat females and causes permanent effects on rat males. Little data have been gathered on the associations between PBDEs exposure and birth outcome and female menstruation characteristics in both epidemiological and animal studies. The aim of this study was to examine how PBDEs in breast milk are associated with infant birth outcome and maternal menstruation characteristics. Study participants were healthy women recruited from central Taiwan between December 2000 and November 2001. Twelve congener levels of PBDEs (BDE-17, 28, 47, 66, 85, 99, 100, 138, 153, 154, 183, 209) in 20 breast milk samples were measured by gas chromatography with high resolution mass spectrometer. The mean level of PBDEs in breast milk was 3.93+/-1.74 ng/g lipid. The estimated PBDE daily intake for a breastfed infant was 20.6 ng/kg b.w./day after delivery. After maternal age, pre-pregnant BMI, and parity were adjusted, increased PBDEs in breast milk was related with decreased birth outcome, particularly for birth weight and length, chest circumference, and Quetelet's index of infants. No significant differences in PBDEs were found between the two groups of menstrual cycle length higher and lower than 30 days after we adjusted for maternal age, pre-pregnant BMI, and parity. In utero exposure to low doses of PBDEs may result in lower birth weight and short or birth length. Our findings are limited based on the low doses of PBDEs and the small sampling size.     

Health impact and damage cost assessment of pesticides in Europe

Health impacts from pesticide use are of continuous concern in the European population, requiring a constant evaluation of European pesticide policy. However, health impacts have never been quantified accounting for specific crops contributing differently to overall human exposure as well as accounting for individual substances showing distinct environmental behavior and toxicity. We quantify health impacts and related damage costs from exposure to 133 pesticides applied in 24 European countries in 2003 adding up to almost 50% of the total pesticide mass applied in that year. Only 13 substances applied to 3 crop classes (grapes/vines, fruit trees, vegetables) contribute to 90% of the overall health impacts of about 2000 disability-adjusted life years in Europe per year corresponding to annual damage costs of 78 million Euro. Considering uncertainties along the full impact pathway mainly attributable to non-cancer dose–response relationships and residues in treated crops, we obtain an average burden of lifetime lost per person of 2.6 hours (95% confidence interval between 22 seconds and 45.3 days) or costs per person over lifetime of 12 Euro (95% confidence interval between 0.03 Euro and 5142 Euro), respectively. 33 of the 133 assessed substances accounting for 20% of health impacts in 2003 are now banned from the European market according to current legislation. The main limitation in assessing human health impacts from pesticides is related to the lack of systematic application data for all used substances. Since health impacts can be substantially influenced by the choice of pesticides, the need for more information about substance application becomes evident.     

Cumulative health risk assessment of 17 perfluoroalkylated and polyfluoroalkylated substances (PFASs) in the Swedish population

Humans are simultaneously exposed to a multitude of chemicals. Human health risk assessment of chemicals is, however, normally performed on single substances, which may underestimate the total risk, thus bringing a need for reliable methods to assess the risk of combined exposure to multiple chemicals. Per- and polyfluoroalkylated substances (PFASs) is a large group of chemicals that has emerged as global environmental contaminants. In the Swedish population, 17 PFASs have been measured, of which the vast majority lacks human health risk assessment information. The objective of this study was to for the first time perform a cumulative health risk assessment of the 17 PFASs measured in the Swedish population, individually and in combination, using the Hazard Index (HI) approach. Swedish biomonitoring data (blood/serum concentrations of PFASs) were used and two study populations identified: 1) the general population exposed indirectly via the environment and 2) occupationally exposed professional ski waxers. Hazard data used were publicly available toxicity data for hepatotoxicity and reproductive toxicity as well as other more sensitive toxic effects. The results showed that PFASs concentrations were in the low ng/ml serum range in the general population, reaching high ng/ml and low μg/ml serum concentrations in the occupationally exposed. For those congeners lacking toxicity data with regard to hepatotoxicity and reproductive toxicity read-across extrapolations was performed. Other effects at lower dose levels were observed for some well-studied congeners. The risk characterization showed no concern for hepatotoxicity or reproductive toxicity in the general population except in a subpopulation eating PFOS-contaminated fish, illustrating that high local exposure may be of concern. For the occupationally exposed there was concern for hepatotoxicity by PFOA and all congeners in combination as well as for reproductive toxicity by all congeners in combination, thus a need for reduced exposure was identified. Concern for immunotoxicity by PFOS and for disrupted mammary gland development by PFOA was identified in both study populations as well as a need of additional toxicological data for many PFAS congeners with respect to all assessed endpoints.     

Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth

Growth of the fetus is highly sensitive to environmental perturbations, and disruption can lead to problems in pregnancy as well as later in life. This study investigates the relationship between maternal exposure to common plasticizers in pregnancy and fetal growth. Participants from a longitudinal birth cohort in Boston were recruited early in gestation and followed until delivery. Urine samples were collected at up to four time points and analyzed for concentrations of phthalate metabolites and bisphenol A (BPA). Ultrasound scans were performed at four time points during pregnancy for estimation of growth parameters, and birthweight was recorded at delivery. Growth measures were standardized to a larger population. For the present analysis we examined cross-sectional and repeated measures associations between exposure biomarkers and growth estimates in 482 non-anomalous singleton pregnancies. Cross-sectional associations between urinary phthalate metabolites or BPA and growth indices were imprecise. However, in repeated measures models, we observed significant inverse associations between di-2-ethylhexyl phthalate (DEHP) metabolites and estimated or actual fetal weight. An interquartile range increase in summed DEHP metabolites was associated with a 0.13 standard deviation decrease in estimated or actual fetal weight (95% confidence interval = − 0.23, − 0.03). Associations were consistent across different growth parameters (e.g., head circumference, femur length), and by fetal sex. No consistent associations were observed for other phthalate metabolites or BPA. Maternal exposure to DEHP during pregnancy was associated with decreased fetal growth, which could have repercussive effects.     

Endocrine disrupting pesticides: implications for risk assessment

Endocrine disrupting (ED) chemicals are compounds that alter the normal functioning of the endocrine system, potentially causing disease or deformity in organisms and their offspring. Pesticides are used widely to kill unwanted organisms in crops, public areas, homes and gardens and medicinally to kill parasites. Many are proven or suspected to be EDs. Ancient physiological similarities between different vertebrate groups suggest that disorders observed in wildlife may indicate risks to humans. This makes accurate risk assessment and effective legislation difficult. In this paper, the hazardous properties of pesticides which are known to have ED properties are reviewed in order to assess the implications for risk assessment. As well as data on sources of exposure in the United Kingdom (UK) an assessment of the evidence on the health effects of ED pesticides is also included. In total, 127 have been identified from the literature and their effects and modes of action are listed in this paper. Using the UK as a case study, the types and quantities of pesticides used, and their methods of application are assessed, along with their potential pathways to humans. In the UK reliable data are available only for agricultural use, so non-agricultural routes of pesticide exposure have been poorly quantified. The exposure of people resident in or visiting rural areas could also have been grossly under-estimated. Material links between ED pesticide use and specific illnesses or deformities are complicated by the multifactorial nature of disease, which can be affected by factors such as diet. Despite these difficulties, a large body of evidence has accumulated linking specific conditions to ED pesticides in wildlife and humans. A more precautionary approach to the use of ED pesticides, especially for non-essential purposes is proposed.     

Prenatal exposure to environmental contaminants and behavioural problems at age 7–8 years

Animal studies showed that the developing brain is particularly sensitive to chemical exposure. Human studies carried out in areas with high exposures have proven neurodevelopmental disorders in relation to e.g. lead and PCBs. Whether these chemicals are associated with behavioural problems in childhood at current environmental levels is not well known. Therefore, we assessed the association between prenatal exposure to lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p′-DDE and behavioural problems in 7–8 year old children. Prenatal exposure data were obtained from the Flemish mother–new-born cohort. Lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p′-DDE were analysed in cord blood. When the child reached 7–8 years, 270 mothers completed the Strengths and Difficulties Questionnaire assessing their children's behavioural health. We found that doubling the prenatal lead exposure (cord blood lead levels) was associated with a 3.43 times higher risk for hyperactivity in both boys and girls. In addition, total difficulties were 5.08 times more likely in the highest tertile for prenatal lead exposure compared to the lowest tertile. In girls, total difficulties were 4.92 more likely when doubling cord blood p,p′-DDE, whereas no significant association was found in boys. Further, we noted in boys a 1.53 times higher risk for emotional problems when doubling cord blood cadmium, whereas no significant association was found in girls. These results indicate that the presence of environmental contaminants influences the mental health of the next generation.     

Environmental occurrence,analysis and human exposure to the flame retardant tetrabromobisphenol-A (TBBP-A)-A review

TBBP-A is a high production volume chemical applied widely as a flame retardant in printed circuit boards. Recent studies have raised concern over potential harmful implications of TBBP-A exposure in human and wildlife, leading to its classification under group 2A “Probably carcinogenic to humans” by the International Agency for Research on Cancer. This article provides a comprehensive review of the available literature on TBBP-A analysis, environmental levels and human exposure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been identified as the method of choice for robust, accurate and sensitive analysis of TBBP-A in different matrices. TBBP-A has been detected in almost all environmental compartments all over the world, rendering it a ubiquitous contaminant. Human exposure studies revealed dust ingestion and diet as the major pathways of TBBP-A exposure in the general population. Toddlers are likely to be more exposed than adults via accidental indoor dust ingestion. Moreover, exposure to TBBP-A may occur prenatally and via breast milk. There are no current restrictions on the production of TBBP-A in the EU or worldwide. However, more research is required to characterise human exposure to TBBP-A in and around production facilities, as well as in e-waste recycling regions.     

Neurotoxic and genotoxic effects of methylmercury

The toxic form of methylmercury is of concern in terms of its neurotoxicity, genotoxicity and reproductive toxicity. Extensive research has been carried out on the effects of exposure to high levels of this toxic compound, but this is not true for research on exposure to lower levels. The harmful effects of methylmercury are a cause for concern irrespective of the exposure levels. The problem becomes more serious because of biomagnifications of methylmercury. Disorders may develop during neonatal stage and then develop further during the lifetime. The common effects which can be seen are retarded brain development and permanent disorders like cerebral palsy. This can also cause neurogenerative disorders like Alzheimer’s and Parkinson’s. Research on animals has also shown toxicity. Inorganic Hg was found to be present in brains of neonatal rats, in monkeys prenatal exposure to MeHg resulted in a reduced number of births, and birds laid a lesser number of eggs and the infant mortality rate was higher.     

An approach to comparative assessments of potential health risks from exposure to radionuclides and hazardous chemicals

The need to compare potential health risks to the public associated with different activities that can result in releases of hazardous substances to the environment is becoming increasingly important in decision-making. In making such comparisons, it is desirable to use equivalent indicators of potential health risks for radionuclides, chemical carcinogens, and noncarcinogenic hazardous chemicals. Current approaches to risk assessment that were developed for purposes of protecting human health do not provide equivalent indicators of potential risks from exposure to radionuclides and hazardous chemicals. Comparisons of environmental concentrations or calculated exposures or risks with standards for protection of public health also do not provide equivalent indicators of potential risks. We propose a simple approach to comparative risk assessments in which calculated exposures to any hazardous substances are expressed relative to no-observed-effect levels (NOELs) or, preferably, lower confidence limits of benchmark doses (BMDLs) in humans. This approach provides an equivalent, science-based indicator of the relative risks posed by different exposures to any hazardous substances.     

Chlorinated paraffins in indoor air and dust: concentrations, congener patterns, and human exposure

Chlorinated paraffins (CPs) are large production volume chemicals used in a wide variety of commercial applications. They are ubiquitous in the environment and humans. Human exposure via the indoor environment has, however, been barely investigated. In the present study 44 indoor air and six dust samples from apartments in Stockholm, Sweden, were analyzed for CPs, and indoor air concentrations are reported for the first time. The sumCP concentration (short chain CPs (SCCPs) and medium chain CPs (MCCPs)) in air ranged from <5-210 ng m(-3) as quantified by gas chromatography coupled to electron ionization tandem mass spectrometry (GC/EI-MS/MS). Congener group patterns were studied using GC with electron capture negative ionization MS (GC/ECNI-MS). The air samples were dominated by the more volatile SCCPs compared to MCCPs. SumCPs were quantified by GC/EI-MS/MS in the dust samples at low μg g(-1) levels, with a chromatographic pattern suggesting the prevalence of longer chain CPs compared to air. The median exposure to sumCPs via the indoor environment was estimated to be ~1 μg day(-1) for both adults and toddlers. Adult exposure was dominated by inhalation, while dust ingestion was suggested to be more important for toddlers. Comparing these results to literature data on dietary intake indicates that human exposure to CPs from the indoor environment is not negligible.     

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: A review

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted.     

Perfluoroalkyl substances in human milk: A first survey in Italy

Due to their widespread diffusion, perfluoroalkyl substances (PFASs) have been frequently found in the environment and in several animal species. It has been demonstrated that they can easily reach also humans, mainly through diet. Being lactation a major route of elimination of these contaminants, their occurrence in human milk is of particular interest, especially considering that it generally represents the unique food source for newborns. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), the two most important compounds of this family, have been frequently found in human milk at variable concentrations, but still limited data are available. The present study, the first conducted in Italy capable to detect these pollutants at ultra-trace levels by UPLC-MS/MS, confirmed the role of lactation as a relevant source of exposure for breastfed children. The measured concentrations ranged between 15 and 288 ng/L for PFOS and between 24 and 241 ng/L for PFOA. Moreover, mean concentrations and frequencies of both analytes resulted higher in milk samples provided by primiparous women, suggesting that the risk of intake might be higher for first-borns. Finally, comparing these results with previous data, PFOS gradual decrease over time since year 2000 was confirmed.