Diet has long been known to modify physiology during development and adulthood. However, due to a growing number of manufactured contaminants and additives over the last few decades, diet has increasingly become a source of exposure to chemicals that has been associated with adverse health risks. Sources of food contaminants include the environment, crops treated with agrochemicals, inappropriate storage (e.g., mycotoxins) and migration of xenobiotics from food packaging and food production equipment. Hence, consumers are exposed to a mixture of xenobiotics, some of which are endocrine disruptors (EDs). The complex interactions between immune function and brain development and their orchestration by steroid hormones are insufficiently understood in human populations, and little is known about the impact on immune-brain interactions by transplacental fetal exposure to EDs via maternal diet. To help to identify the key data gaps, this paper aims to present (a) how transplacental EDs modify immune system and brain development, and (b) how these mechanisms may correlate with diseases such as autism and disturbances of lateral brain development. Attention is given to disturbances of the subplate, a transient structure of crucial significance in brain development. Additionally, we describe cutting edge approaches to investigate the developmental neurotoxicity of EDs, such as the application of artificial intelligence and comprehensive modelling. In the future, highly complex investigations will be performed using virtual brain models constructed using sophisticated multi-physics/multi-scale modelling strategies based on patient and synthetic data, which will enable a greater understanding of healthy or disturbed brain development.

[This corrects the article DOI: 10.1093/eep/dvy028.][This corrects the article DOI: 10.1093/eep/dvy028.].

Assessment of changes in DNA methylation (DNA-m) has the potential to identify adverse environmental exposures. To examine DNA-m among a subset of participants (n = 369) in the Isle of Wight birth cohort who reported variable near resident traffic frequencies. We used self-reported frequencies of heavy vehicles passing by the homes of study subjects as a proxy measure for TRAP, which were: never, seldom, 10 per day, 1-9 per hour and > 10 per hour. Methylation of cytosine-phosphate-guanine (CpG) dinucleotide sequences in the DNA was assessed from blood samples collected at age 18 years (n = 369) in the F1 generation. We conducted an epigenome wide association study to examine CpGs related to the frequency of heavy vehicles passing by subjects' homes, and employed multiple linear regression models to assess potential associations. We repeated some of these analysis in the F2 generation (n = 140). Thirty-five CpG sites were associated with heavy vehicular traffic. After adjusting for confounders, we found 23 CpGs that were more methylated, and 11 CpGs that were less methylated with increasing heavy vehicular traffic frequency among all subjects. In the F2 generation, 2 of 31 CpGs were associated with traffic frequencies and the direction of the effect was the same as in the F1 subset while differential methylation of 7 of 31 CpG sites correlated with gene expression. Our findings reveal differences in DNA-m in participants who reported higher heavy vehicular traffic frequencies when compared to participants who reported lower frequencies.

BACKGROUNDThe authors conducted a retrospective cohort mortality study on police officers from 1950-2005.METHODSStandardized Mortality Ratio (SMR) analyses were conducted separately for white male (n=2761), black (n=286), and female (n=259) officers.RESULTSMortality from all causes of death combined for white male officers was significantly higher than expected (SMR=1.20; 95% confidence interval (CI) =1.14-1.26). Increased mortality was also seen for all malignant neoplasms combined (SMR=1.32; 1.19-1.46), all benign neoplasms combined (SMR=2.50; 1.08-4.93), and all diseases of the circulatory system combined (SMR=1.11; 1.02-1.19). The elevated mortality for all malignant neoplasms was primarily due to statistically significant excesses in cancers of the esophagus, colon, respiratory system, Hodgkin's disease and leukemia. Black officers had lower than expected mortality from all causes (SMR=0.45; 0.18-0.92) while female officers had elevated all-cause mortality (SMR=2.17; 1.12-3.79).CONCLUSIONSFindings of increased risk for malignant neoplasms should be replicated and studied in relation to measured risk factors.

Perfluorinated compounds have been manufactured in large quantities and used in myriad industrial processes and commercial applications. The aim of this preliminary study was to generate hypotheses with regard to differences in body burdens of perfluoroalkyl acids, among a sub-sample of participants from the New York State Angler Cohort Study, over a time interval during which no known substantial changes occurred in US manufacturing practices or commercial use. Paired serum specimens, collected from 15 subjects in 1993–1994 (time 1), and in 1995–1997 (time 2), with a minimum interval of 2.5 years, were assayed for PFDA, PFHpA, PFHxS, PFNA, PFOA, PFOS, PFOSA and PFUnDA using HPLC with ES-MS/MS. By subject, differences in concentrations between time 1 and time 2 were estimated, employing paired t-tests, correlations, and multivariable linear regression to accommodate heterogeneity in duration between specimens, and in time 1 concentrations. A statistically significant (P < 0.05) adjusted mean decrease of 0.16 ng mL−1 (18.8%) between time 1 and 2 was detected for PFNA, and an adjusted mean increase of 0.54 ng mL−1 (56.8%) was detected for PFOA. The results of this study may be indicative of short-term changes in human body burdens of PFNA and PFOA in association with local exposure sources.

BACKGROUNDConsumption of fish contaminated with polychlorinated biphenyls (PCBs) and prenatal PCB serum concentrations have been associated with a longer time-to-pregnancy (TTP). However, the relationship between preconception serum PCBs concentrations and TTP has not been previously studied.METHODSEighty-three women (contributing 442 menstrual cycles) planning pregnancies completed daily diaries regarding menstruation, intercourse, home pregnancy test results, and reported use of alcohol and cigarettes. TTP denoted the number of observed menstrual cycles required for pregnancy. Preconception blood specimens underwent toxicologic analysis for 76 PCB congeners via gas chromatography with electron capture; serum lipids were quantified with enzymatic methods. A priori, PCB congeners were summed into a total and three groupings-estrogenic, anti-estrogenic and other-and entered into discrete analogs of Cox models with time-varying covariates to estimate fecundability odds ratios (FOR) and corresponding 95% confidence intervals (CIs).RESULTSEstrogenic and anti-estrogenic PCB concentrations (ng/g serum) conferred reduced FORs in fully adjusted models (0.32; 95% CI 0.03, 3.90 and 0.01: 95% CI < 0.00, 1.99, respectively). Reduced FORs (0.96) were observed for alcohol consumption standardized to a 28-day menstrual cycle in the same adjusted model (FOR = 0.96; 95% CI 0.93, 1.00).CONCLUSIONSThese data suggest that environmental exposures including those amenable to change, such as alcohol consumption, may impact female fecundity. The findings are sensitive to model specification and PCB groupings, underscoring the need to further assess the impact of chemical mixtures on sensitive reproductive outcomes, such as TTP, especially in the context of lifestyle factors which are amenable to change, thereby improving reproductive health.