Phthalate acid esters (PAEs) are environmental endocrine disruptors that can interfere with endocrine processes and cause adverse reproductive outcomes. The link between PAE exposure and unexplained recurrent spontaneous abortion (URSA) remains unknown. In this study, nine urinary metabolites of PAEs (mPAEs) were measured in 594 URSA cases and 569 healthy controls. The measured mPAEs were ubiquitously detected and present at higher levels (median: 203 ng/mL) in the URSA cases than in the controls (median: 161 ng/mL). Multiple logistic regression analysis showed that URSA was associated with higher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mono (2-ethylhexyl) phthalate (mEHP), and mono-ethyl phthalate (mEP) and lower concentrations of mono-isobutyl phthalate (miBP). Moreover, a quantile-based g-computation (QGC) model revealed a positive association between mPAEs mixture and URSA. The URSA cases showed significantly higher concentrations of di-(2-ethylhexyl) phthalate (DEHP) than the controls. This was consistent with the health risk assessment, which suggested that DEHP is the main contributors to potential non-carcinogenic risk. DEHP accounted for over 80% of total risk. The large case-control study results suggest that PAE exposure may increase the risk of URSA, and that policy-makers and public health experts should pay more attention to DEHP exposure.

Technological advancements make lives safer and more convenient. Unfortunately, many of these advances come with costs to susceptible individuals and public health, the environment, and other species and ecosystems. Synthetic chemicals in consumer products represent a quintessential example of the complexity of both the benefits and burdens of modern living. How we navigate this complexity is a matter of a society\'s values and corresponding principles.
We aimed to develop a series of ethical principles to guide decision-making within the landscape of environmental health, and then apply these principles to a specific environmental chemical, oxybenzone. Oxybenzone is a widely used ultraviolet (UV) filter added to personal care products and other consumer goods to prevent UV damage, but potentially poses harm to humans, wildlife, and ecosystems. It provides an excellent example of a chemical that is widely used for the alleged purpose of protecting human health and product safety, but with costs to human health and the environment that are often ignored by stakeholders.
We propose six ethical principles to guide environmental health decision-making: principles of sustainability, beneficence, non-maleficence, justice, community, and precautionary substitution. We apply these principles to the case of oxybenzone to demonstrate the complex but imperative decision-making required if we are to address the limits of the biosphere\'s regenerative rates. We conclude that both ethical and practical considerations should be included in decisions about the commercial, pervasive application of synthetic compounds and that the current flawed practice of cost-benefit analysis be recognized for what it is: a technocratic approach to support corporate interests.

OBJECTIVE: Our study aimed to explore the effect of parental occupational exposure to endocrine disrupting chemicals (EDCs) on the development of congenital heart diseases (CHDs) in the offspring, and to compare job-exposure matrix (JEM)-assessed and self-reported occupational exposures with each other.
METHODS: Live-born infants born in 2007-2008 were selected from the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities Study. 577 cases with any CHDs were compared to 1731 matched controls. Parental periconceptional occupational exposure to EDCs was assessed by a JEM and by questionnaire-based self-reporting of parents. Multivariate conditional logistic regression analyses were conducted to explore associations between parental occupational exposure to EDCs and the entire spectrum of CHDs and by CHD subtypes in the offspring. Kappa statistics were also performed to determine the consistency among JEM-assessed and self-reported occupational exposure of parents.
RESULTS: JEM-assessed paternal exposure to polychlorinated organic substances, phthalates, biphenolic compounds, and solvents were significantly associated with the entire spectrum of CHDs. Ventricular septal defects were significantly associated with paternal self-reported exposure to pesticides, while atrial septal defects were significantly associated to paternal JEM-assessed phthalate exposure. Paternal solvent exposure was significantly associated with atrial septal defects and right ventricle outflow tract obstructions. JEM-assessed and self-reported exposures to pesticides, heavy metals, and solvents exhibited poor agreement for mothers and slight agreement for fathers.
CONCLUSIONS: Even though parental occupational exposure to EDCs seems to have a minor impact on the occurrence of CHDs, the results of biological and environmental monitoring should be taken into consideration as well.

Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence.
The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence.
Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm.
DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.

BACKGROUND: Growing evidence demonstrates that exposure to organophosphate flame retardants (PFRs) is widespread and that these chemicals can alter thyroid hormone regulation and function. We investigated the relationship between PFR exposure and thyroid cancer and whether individual or temporal factors predict PFR exposure.
METHODS: We analyzed interview data and spot urine samples collected in 2010-2013 from 100 incident female, papillary thyroid cancer cases and 100 female controls of a Connecticut-based thyroid cancer case-control study. We measured urinary concentrations of six PFR metabolites with mass spectrometry. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) for continuous and categories (low, medium, high) of concentrations of individual and summed metabolites, adjusting for potential confounders. We examined relationships between concentrations of PFR metabolites and individual characteristics (age, smoking status, alcohol consumption, body mass index [BMI], income, education) and temporal factors (season, year) using multiple linear regression analysis.
RESULTS: No PFRs were significantly associated with papillary thyroid cancer risk. Results remained null when stratified by microcarcinomas (tumor diameter ≤ 1 cm) and larger tumor sizes (> 1 cm). We observed higher urinary PFR concentrations with increasing BMI and in the summer season.
CONCLUSIONS: Urinary PFR concentrations, measured at time of diagnosis, are not linked to increased risk of thyroid cancer. Investigations in a larger population or with repeated pre-diagnosis urinary biomarker measurements would provide additional insights into the relationship between PFR exposure and thyroid cancer risk.

A number of pesticides are suspected or proved to act as endocrine disruptor compounds (EDCs). In the present survey of the literature, we try to define the main issues to be considered to classify individual pesticides as EDC or not.

Socioeconomic analysis is currently used in the Europe Union as part of the regulatory process in Regulation Registration, Evaluation and Authorisation of Chemicals (REACH), with the aim of assessing and managing risks from dangerous chemicals. The political impact of the socio-economic analysis is potentially high in the authorisation and restriction procedures, however, current socio-economic analysis dossiers submitted under REACH are very heterogeneous in terms of methodology used and quality. Furthermore, the economic literature is not very helpful for regulatory purposes, as most published calculations of health costs associated with chemical exposures use epidemiological studies as input data, but such studies are rarely available for most substances. The quasi-totality of the data used in the REACH dossiers comes from toxicological studies.
This paper assesses the use of the integrated probabilistic risk assessment, based on toxicological data, for the calculation of health costs associated with endocrine disrupting effects of triclosan. The results are compared with those obtained using the population attributable fraction, based on epidemiological data.
The results based on the integrated probabilistic risk assessment indicated that 4894 men could have reproductive deficits based on the decreased vas deferens weights observed in rats, 0 cases of changed T3 levels, and 0 cases of girls with early pubertal development. The results obtained with the Population Attributable Fraction method showed 7,199,228 cases of obesity per year, 281,923 girls per year with early pubertal development and 88,957 to 303,759 cases per year with increased total T3 hormone levels. The economic costs associated with increased BMI due to TCS exposure could be calculated. Direct health costs were estimated at €5.8 billion per year.
The two methods give very different results for the same effects. The choice of a toxicological-based or an epidemiological-based method in the socio-economic analysis will therefore significantly impact the estimated health costs and consequently the political risk management decision. Additional work should be done for understanding the reasons of these significant differences.

BACKGROUND: The U.S. Environmental Protection Agency\'s (EPA\'s) Toxicity Forecaster (ToxCast) is a potential tool for chemical prioritization, hazard identification, and risk assessment. We conducted a case study to compare ToxCast data with endpoints from other in vitro and in vivo studies for two data-rich pesticides: endosulfan and methidathion.
METHODS: ToxCast assays for endocrine disruption, development (zebrafish), and neurotoxicity were qualitatively compared to traditional neurotoxicity, developmental and reproductive toxicity findings. We also used in vitro-in vivo extrapolation to convert half-maximal activity concentrations in active ToxCast assays to rat oral equivalent doses, and quantitatively compared these to the lowest observable effect level (LOEL) from in vivo studies.
RESULTS: Endosulfan was inactive for GABAA R, unlike in vivo; but active with dopamine transporter assays and was neurotoxic in zebrafish as expected. Methidathion was not active for these endpoints in vivo or in vitro. Acetylcholinesterase inhibition was ToxCast-inactive, although both pesticides are inhibitors in vivo. ToxCast results were generally inactive for endosulfan estrogen receptor agonism and androgen receptor antagonism unlike in vivo. Calculated oral equivalent doses for estrogen receptor and androgen receptor pathways and for zebrafish assays for both compounds were generally consistent with in vivo LOELs. Endosulfan showed neurotoxicity and both pesticides showed developmental effects in the zebrafish assays, although methidathion is not developmentally toxic in vivo.
CONCLUSIONS: ToxCast\'s predictions showed concordance on some endpoints and nonconcordance, consisting mainly of false inactives, in several critical endpoints, likely due to a lack of metabolic activation and limitations in assay design. Zebrafish assays were good predictors of developmental toxicity and neurotoxicity for endosulfan.