The role of phthalate esters in autism development: A systematic review.

BACKGROUND: Available evidence implicates environmental factors in the pathogenesis of autism spectrum disorders (ASD). However, the role of specific environmental chemicals such as phthalate esters that influence ASD risk remains elusive. This paper systematically reviews published evidences on association between prenatal and/or childhood exposure to phthalate and ASD. METHODS: Studies pertaining to systematic literature search from Scopus, PubMed, PsycInfo and Web of Science prior to December 2015 were identified. The authors included studies which assessed the effect of exposure to phthalates on occurrence of ASD. This comprehensive bibliographic search identified five independent studies. Each eligible paper was summarized with respect to its methods and results with particular attention to study design and exposure assessment. Because of the heterogeneity in the type of included studies, different methods of assessing exposure to phthalates and the use of different statistics for summarizing the results, meta-analysis could not be used to combine the results of included studies. RESULTS: The results of this systematic review have revealed the limited number of studies conducted and assessed phthalate exposure. Seven studies were regarded as relevant to the objectives of this review. Two of them did not measure phthalate exposure directly and did not result in quantitative results. Out of the five studies in which phthalate exposure was mainly measured by the examining biomarkers in biological samples, two were cohort studies (one with positive results and another one with not clear association). Among the three case control studies, two of them showed a significant relation between exposure to phthalate and ASD and the last case control study had negative results. Indeed, this case control studies showed a compromised phthalate metabolite glucuronidation pathway, as a probable explanation of mechanism of the relation between phthalate exposure and ASD. CONCLUSIONS: This review reveals evidence showing a connection between exposure to phthalates and ASD. Nevertheless, further research is needed with appropriate attention to exposure assessment and relevant pre and post-natal cofounders.

Endocrine disruptor phthalates in bottled water: daily exposure and health risk assessment in pregnant and lactating women.

Over the last decade, the consumption of water bottled in polyethylene terephthalate (PET) has considerably increased, raising concerns over water quality and packaged materials. This study aims to investigate the levels of the anti-androgenic phthalates including bis-(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBP), in bottled water and its corresponding health risks in pregnant and lactating women. The phthalate levels were measured in six different brands of bottled water exposed to temperatures ranging between -18 and 40 °C and sunlight for 45 days. The phthalate was quantified using the gas chromatography-mass spectrometry (GC-MS). In addition, the non-carcinogenic effects were assessed using hazard quotient (HQ) approach, and cumulative health risk assessment was performed on the basis of hazard index (HI) calculation. In order to assess the carcinogenic risk due to the possible carcinogen DEHP (group 2B), the excess lifetime cancer risk (ELCR) was used. DEHP and DBP contaminants were detected at different storage conditions in all of the bottled water samples during the storage time. BBP was only detected at high temperature (≥25 °C) and outdoor conditions. The maximum concentrations of all phthalates were observed when water samples were kept at 40 °C. In contrast, storage at freezing conditions had no significant effect on the concentration level of all phthalates. The estimated intake by women was between 0.0021 µg/kg/day for BBP and 0.07 µg/kg/day for DEHP. The highest HQ for phthalate intake via bottled water consumption was much lower than 1 (HQ < 0.004), which implies that adverse effects are very unlikely to occur. The execution of a cumulative risk assessment for combined phthalate exposure demonstrated that the HIs for anti-androgenic effect were lower than 1 in all of the conditions. Furthermore, ELCR for DEHP based on the highest detected level was found to be less than 10(-6), which is considered acceptable. Our results prove that the levels of phthalates in bottled water are not a health concern for pregnant and lactating women. Consequently, PET-bottled water is not a major contributor to phthalate intake for most individuals.

Microbial evaluation of fresh, minimally-processed vegetables and bagged sprouts from chain supermarkets.

The aim of this study was to evaluate the bacterial and fungal quality of minimally-processed vegetables (MPV) and sprouts. A total of 116 samples of fresh-cut vegetables, ready-to-eat salads, and mung bean and wheat sprouts were randomly collected and analyzed. The load of aerobic mesophilic bacteria was minimum and maximum in the fresh-cut vegetables and fresh mung bean sprouts respectively, corresponding to populations of 5.3 and 8.5 log CFU/g. E. coli O157:H7 was found to be absent in all samples; however,  other E. coli strains were detected in 21 samples (18.1%), and Salmonella spp. were found in one mung bean (3.1%) and one ready-to-eat salad sample (5%). Yeasts were the predominant organisms and were found in 100% of the samples. Geotrichum, Fusarium, and Penicillium spp. were the most prevalent molds in mung sprouts while Cladosporium and Penicillium spp. were most frequently found in ready-to-eat salad samples. According to results from the present study, effective control measures should be implemented to minimize the microbiological contamination of fresh produce sold in Tehran, Iran.

Interpreting biomonitoring data: Introducing the international human biomonitoring (i-HBM) working group's health-based guidance value (HB2GV) dashboard.

Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.

Prenatal blood levels of some toxic metals and the risk of spontaneous abortion.

High-level toxic metal exposure has become rare in the recent years. Although, it has not known whether relatively lower exposure may adversely affect human reproductive system. Spontaneous abortion (SA) is a serious reproductive problem, which, in many cases, the cause(s) is not clearly understood. To assess the relationship between prenatal blood level of metals and SA risk, we compared blood concentration of some heavy metals in samples taken from mothers recruited in Tehran Environment and Neurodevelopmental Defects (TEND) study conducted on apparently healthy pregnant women in Tehran, Iran who subsequently experienced spontaneous abortion with mothers who their pregnancy ended to live births. During early gestation, 206 women were enrolled to the survey and followed up till fetal abortion or baby deliveries occur. Blood metal concentrations were measured using an inductively coupled plasma mass spectrometer. The mean blood levels of lead, antimony, and nickel were higher in SA than ongoing pregnancy; however, this difference was not statistically significant. When adjusted for covariates, the logistic regression analysis showed significant association between maternal age and the risk of SA in all models. Among toxic metals only antimony had a noticeable positive relation with the risk of SA (OR: 1.65, 95% CI:1.08-2.52, P value: 0.02). Pearson's correlation coefficient showed significant (P < 0.05) positive correlations among prenatal blood metals levels, except for nickel. Although the present study failed to provide strong evidence for the effects of toxic metals on the occurrence of SA at the relatively low-levels, these metals should be avoided in women who plan pregnancy and/or during the early stages of gestation to prevent the chance of adverse effects.

Building a European exposure science strategy.

Exposure information is a critical element in various regulatory and non-regulatory frameworks in Europe and elsewhere. Exposure science supports to ensure safe environments, reduce human health risks, and foster a sustainable future. However, increasing diversity in regulations and the lack of a professional identity as exposure scientists currently hamper developing the field and uptake into European policy. In response, we discuss trends, and identify three key needs for advancing and harmonizing exposure science and its application in Europe. We provide overarching building blocks and define six long-term activities to address the identified key needs, and to iteratively improve guidelines, tools, data, and education. More specifically, we propose creating European networks to maximize synergies with adjacent fields and identify funding opportunities, building common exposure assessment approaches across regulations, providing tiered education and training programmes, developing an aligned and integrated exposure assessment framework, offering best practices guidance, and launching an exposure information exchange platform. Dedicated working groups will further specify these activities in a consistent action plan. Together, these elements form the foundation for establishing goals and an action roadmap for successfully developing and implementing a 'European Exposure Science Strategy' 2020-2030, which is aligned with advances in science and technology.

Tehran environmental and neurodevelopmental disorders (TEND) cohort study: Phase I, feasibility assessment.

PURPOSE: To advance knowledge about childhood neurodevelopmental disorders and study their environmental determinants, we conducted a study in Tehran, Iran to assess the feasibility of prospective birth cohort study. METHODS: We evaluated participation of pregnant women, feasibility of sampling biological material, and health care services availability in Tehran in four steps: (1) first trimester of pregnancy; (2) third trimester of pregnancy; (3) at delivery; and (4) two to three months after delivery. We collected related data through questionnaires, also various biological samples were obtained from mothers (blood, urine, milk and nails-hands and feet) and newborns (umbilical cord blood, meconium, and urine samples) from February 2016 to October 2017. RESULTS: overall 838 eligible pregnant women were approached. The participation rate was 206(25%) in our study and about 185(90%) of subjects were recruited in hospitals. Out of 206 participants in the first trimester, blood, urine, hand nail, and foot nail samples were collected from 206(100%),193(93%), 205(99%), and 205(99%), respectively. These values dropped to 65(54%), 83(69%), 84(70%), and 84(70%) for the remaining participants 120(58%) in the third trimester, respectively. Also, we gathered milk samples from 125(60%) of mothers at two to three months after delivery. CONCLUSION: Our findings suggest that hospitals were better places for recruitment of subjects in a birth cohort in Tehran. We further concluded that birth cohort study recruitment can be improved by choosing appropriate gestational ages. Obtaining the newborn's urine, meconium, and umbilical cord blood were challenging procedures and require good collaboration between hospital staff and researchers.

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals.

This Guidance document describes harmonised risk assessment methodologies for combined exposure to multiple chemicals for all relevant areas within EFSA's remit, i.e. human health, animal health and ecological areas. First, a short review of the key terms, scientific basis for combined exposure risk assessment and approaches to assessing (eco)toxicology is given, including existing frameworks for these risk assessments. This background was evaluated, resulting in a harmonised framework for risk assessment of combined exposure to multiple chemicals. The framework is based on the risk assessment steps (problem formulation, exposure assessment, hazard identification and characterisation, and risk characterisation including uncertainty analysis), with tiered and stepwise approaches for both whole mixture approaches and component-based approaches. Specific considerations are given to component-based approaches including the grouping of chemicals into common assessment groups, the use of dose addition as a default assumption, approaches to integrate evidence of interactions and the refinement of assessment groups. Case studies are annexed in this guidance document to explore the feasibility and spectrum of applications of the proposed methods and approaches for human and animal health and ecological risk assessment. The Scientific Committee considers that this Guidance is fit for purpose for risk assessments of combined exposure to multiple chemicals and should be applied in all relevant areas of EFSA's work. Future work and research are recommended.

Effect of sunlight exposure on phthalates migration from plastic containers to packaged juices.

BACKGROUND: Acidic juices such as lemon juice, vinegar and Verjuice are popular beverages regularly consumed by both children and adults. Various brands of different acidic juices in Iran markets are packaged in disposable plastic bottles. Some evidence suggests that phthalates may immigrate from plastic bottles. METHODS: In this research the influence of sunlight, type of container and storage time on the leaching of phthalates from packaging materials into selected juices was investigated, by analyzing the samples kept in different conditions, before and throughout 2, 4 and 6 months storage time. RESULTS: The mean phthalate concentrations of the examined samples were determined to be between

Association of urinary bisphenol a concentration with type-2 diabetes mellitus.

BACKGROUND: Bisphenol A as an endocrine-disrupting chemical is widely used chemical in the manufacture of polycarbonate plastics and epoxy resin and has become ubiquitous environmental contaminants. Human exposure to Bisphenol A is widespread and recent studies have been shown to be associated with a higher risk for self-reported adverse health outcomes that may lead to insulin resistance and the development of type-2 diabetes mellitus. In this context, we sought to confirm the association between Bisphenol A and diabetes in a community-based analysis of Bisphenol A urinary concentrations investigation in adult population of Iran. METHODS: Regression models were adjusted for age, sex, Body Mass Index, serum triglyceride level and serum cholesterol level and serum creatinine concentration. Main outcomes were reported diagnoses of diabetes that defined according the latest American Diabetes Association guidelines. RESULTS: The median age of the 239 participants was 51.65 years and 119 people had type-2 diabetes mellitus. Urinary Bisphenol A was categorized into two groups based on the median for Bisphenol A (≤0. 85 to >0.85 µg/L). The results of statistical analysis revealed a clear association between hypertension, and type 2 diabetes (P < 0.05). The multi variable-adjusted odds ratio for type-2 diabetes mellitus associated with the group 1 (referent), of urinary Bisphenol A was 57.6 (95% confidence interval: 21.10-157.05; P-value < 0.001). A positive correlation between HbA1c and urinary BPA concentration was observed (r = 0.63, P = 0.001). CONCLUSIONS: Urinary Bisphenol A levels are found to be associated with diabetes independent of traditional diabetes risk factors. Higher Bisphenol A exposure, reflected in higher urinary concentrations of Bisphenol A, is consistently associated with diabetes in the general adult population of the Iran. Studies to clarify the mechanisms of these associations are urgently needed.