Biomonitoring of bisphenol A (BPA) and bisphenol analogues in human milk from South Africa and Canada using a modified QuEChERS extraction method.

A sensitive modified QuEChERS extraction method was developed to assess the levels of free and conjugated bisphenols (BPs) in human milk collected between 2018 and 2019 from two regions of South Africa (the Limpopo Province Vhembe district, n = 194; Pretoria, n = 193) and Canada (Montreal, n = 207). Total BPA (free and conjugated) and BPS were the predominant bisphenols detected in samples from Vhembe and Pretoria, whereas total BPS was the predominant bisphenol detected in Montreal samples. The levels of total BPA in samples from Vhembe and Pretoria ranged between < MDL-18.61 and

Association between prenatal exposure to indoor residual spraying insecticides and infection rates among South African children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE).

In 2021, 53 countries conducted indoor residual spraying (IRS), the application of insecticides such as dichlorodiphenyl trichloroethane (DDT) or pyrethroids to the walls of homes to control malaria. Animal studies show that these insecticides can increase susceptibility to infections but only one human study was conducted in a population from an area where IRS is applied. The aim of the present study was thus to investigate whether maternal exposure to DDT, its breakdown product dichlorodiphenyl dichloroethylene (DDE) or pyrethroid insecticides is associated with symptoms of infection among children living in a region of South Africa were IRS is conducted annually. As part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) we measured maternal serum concentrations of DDT and DDE, and urinary concentrations of four pyrethroid metabolites in peripartum samples. Poisson regression models with robust variance estimates were used to investigate associations with the rates of infection symptoms between ages 3.5-5 years among 629 children as assessed based on caregiver interviews. Multiple pyrethroid metabolites were associated with infection symptoms. For instance, cis-DBCA was associated with increased rates of ear infection (Incidence Rate Ratio for a 10-fold increase (IRR10) = 1.4; 95 % Confidence Interval (CI) = 1.0, 2.1) and persistent diarrhea (IRR10 = 2.1; 95 % CI = 1.2, 3.9), trans-DCCA was associated with increased rates of colds in children (IRR10 = 1.3; 95 % CI = 1.0, 1.6) and persistent fever (IRS10 = 1.4; 95 % CI = 1.0, 2.0), and 3-PBA was associated with increased rates of persistent fever (IRR10 = 1.8; 95 % CI = 1.0, 3.0). We found limited evidence of association between maternal DDE and DDT serum concentrations and infection symptoms. Results suggest that prenatal exposure to pyrethroid insecticides may be associated with infections among children from an area where IRS is conducted.

The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome-a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men.

BACKGROUND: The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) accumulates in marine mammals and fish. DDT and p,p'-DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome. OBJECTIVES: The objective of this study was to assess the sperm epigenome in relation to p,p'-DDE serum levels between geographically diverse populations. METHODS: In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of p,p'-DDE serum levels (mean=870.734±134.030 ng/mL). We assessed the sperm epigenome in relation to serum p,p'-DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm. RESULTS: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression. DISCUSSION: These findings suggest that DDT and p,p'-DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.

Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE).

BACKGROUND: Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area. METHODS: We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. At 3.5-year and 5-year follow-up visits, caregivers of 647 and 620 children, respectively, were queried about children's respiratory allergy symptoms based on validated instruments. We applied marginal structural models for repeated outcomes to estimate associations between biomarker concentrations and asthma diagnosis as well as respiratory allergy symptoms at ages 3.5 and 5 years. RESULTS: We found that a10-fold increase in maternal urinary cis-DCCA, trans-DCCA and 3-PBA concentrations were associated with more than a doubling in the risk of doctor-diagnosed asthma (cis-DCCA: RR = 2.1, 95% CI = 1.3, 3.3; trans-DCCA: RR = 2.1, 95% CI = 1.1, 3.9; 3-PBA: RR = 2.4, 95% CI = 1.0, 5.8) and an about 80% increase in the risk of wheezing or whistling in the chest (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.0; trans-DCCA: RR = 1.7, 95% CI = 1.1, 2.6; 3-PBA: RR = 1.8, 95% CI = 1.0, 3.3) and suspected asthma (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.1; trans-DCCA: RR = 1.8, 95% CI = 1.1, 2.8). We also observed that higher concentrations of cis-DBCA and 3-PBA were related to increases in the risks of dry cough at night (RR = 3.5, 95% CI = 1.3, 9.5) and seasonal rhinoconjunctivitis (RR = 2.0, 95% CI = 1.1, 3.9), respectively. CONCLUSION: Maternal exposure to pyrethroids may increase the risk of asthma and other respiratory allergy symptoms among preschool children from an IRS area.

Geo-epidemiology of malaria incidence in the Vhembe District to guide targeted elimination strategies, South-Africa, 2015-2018: a local resurgence.

In South Africa, the population at risk of malaria is 10% (around six million inhabitants) and concern only three provinces of which Limpopo Province is the most affected, particularly in Vhembe District. As the elimination approaches, a finer scale analysis is needed to accelerate the results. Therefore, in the process of refining local malaria control and elimination strategies, the aim of this study was to identify and describe malaria incidence patterns at the locality scale in the Vhembe District, Limpopo Province, South Africa. The study area comprised 474 localities in Vhembe District for which smoothed malaria incidence curve were fitted with functional data method based on their weekly observed malaria incidence from July 2015 to June 2018. Then, hierarchical clustering algorithm was carried out considering different distances to classify the 474 smoothed malaria incidence curves. Thereafter, validity indices were used to determine the number of malaria incidence patterns. The cumulative malaria incidence of the study area was 4.1 cases/1000 person-years. Four distinct patterns of malaria incidence were identified: high, intermediate, low and very low with varying characteristics. Malaria incidence increased across transmission seasons and patterns. The localities in the two highest incidence patterns were mainly located around farms, and along the rivers. Some unusual malaria phenomena in Vhembe District were also highlighted as resurgence. Four distinct malaria incidence patterns were found in Vhembe District with varying characteristics. Findings show also unusual malaria phenomena in Vhembe District that hinder malaria elimination in South Africa. Assessing the factors associated with these unusual malaria phenome would be helpful on building innovative strategies that lead South Africa on malaria elimination.

Household living conditions and individual behaviours associated with malaria risk: a community-based survey in the Limpopo River Valley, 2020, South Africa.

BACKGROUND: Over the past decade, implementation of multiple malaria control strategies in most countries has largely contributed to advance the global malaria elimination agenda. Nevertheless, in some regions, seasonal epidemics may adversely affect the health of local populations. In South Africa, Plasmodium falciparum malaria is still present, with the Vhembe District experiencing an incidence rate of 3.79 cases/1000 person-years in 2018, particularly in the Limpopo River Valley, bordering Zimbabwe. To elucidate the complexity of the mechanisms involved in local regular malaria outbreaks, a community-based survey was implemented in 2020 that focused on the relationship between housing conditions and malaria risky behaviours. METHODS: The community-based cross-sectional survey was conducted among the population of three study sites in the Vhembe District, which were selected based on malaria incidence rate, social and health characteristics of inhabitants. The household survey used a random sampling strategy, where data were collected through face-to-face questionnaires and field notes; to described the housing conditions (housing questionnaire), and focus on individual behaviours of household members. Statistical analyses were performed combining hierarchical classifications and logistic regressions. RESULTS: In this study, 398 households were described, covering a population of 1681 inhabitants of all ages, and 439 adults who participated in community-based survey. The analysis of situations at risk of malaria showed that the influence of contextual factors, particularly those defined by the type of habitat, was significant. Housing conditions and poor living environments were factors of malaria exposure and history, regardless of site of investigation, individual preventive behaviours and personal characteristics of inhabitants. Multivariate models showed that, considering all personal characteristics or behaviours of inhabitants, housing conditions such as overcrowding pressures were significantly associated with individual malaria risk. CONCLUSIONS: The results showed the overwhelming weight of social and contextual factors on risk situations. Considering the Fundamental Causes Theory, malaria control policies based on health behaviour prevention, should reinforce access to care or promoting health education actions. Overarching economic development interventions in targeted geographical areas and populations have to be implemented, so that malaria control and elimination strategies can be efficiently and effectively managed.

A review and comparative study of cancer detection using machine learning: SBERT and SimCSE application.

BACKGROUND: Using visual, biological, and electronic health records data as the sole input source, pretrained convolutional neural networks and conventional machine learning methods have been heavily employed for the identification of various malignancies. Initially, a series of preprocessing steps and image segmentation steps are performed to extract region of interest features from noisy features. Then, the extracted features are applied to several machine learning and deep learning methods for the detection of cancer. METHODS: In this work, a review of all the methods that have been applied to develop machine learning algorithms that detect cancer is provided. With more than 100 types of cancer, this study only examines research on the four most common and prevalent cancers worldwide: lung, breast, prostate, and colorectal cancer. Next, by using state-of-the-art sentence transformers namely: SBERT (2019) and the unsupervised SimCSE (2021), this study proposes a new methodology for detecting cancer. This method requires raw DNA sequences of matched tumor/normal pair as the only input. The learnt DNA representations retrieved from SBERT and SimCSE will then be sent to machine learning algorithms (XGBoost, Random Forest, LightGBM, and CNNs) for classification. As far as we are aware, SBERT and SimCSE transformers have not been applied to represent DNA sequences in cancer detection settings. RESULTS: The XGBoost model, which had the highest overall accuracy of 73 ± 0.13 % using SBERT embeddings and 75 ± 0.12 % using SimCSE embeddings, was the best performing classifier. In light of these findings, it can be concluded that incorporating sentence representations from SimCSE's sentence transformer only marginally improved the performance of machine learning models.

COVID-19 and the malaria elimination agenda in Africa: Re-shifting the focus.

The global Coronavirus disease 2019 (COVID-19) pandemic has resulted in public health, political, scientific and private sector response at an unprecedented scale. However, this shift in focus has caused widespread disruption to global health services and has the potential to reverse gains made in efforts to control malaria. If health systems are not able to maintain malaria control interventions while managing the response to the COVID-19 pandemic, malaria cases will increase, thereby placing even more strain on already overtaxed systems. Using a Narrative Review Approach, this commentary explores the impact of COVID-19 on progress made with malaria control and prevention strategies in Africa; and discusses possible mitigation steps to aid community resilience building, through proactive planning and implementation of integrated, inclusive and sustainable strategies to re-shift the focus to attain the malaria elimination goals. We propose strengthening community partnerships, where academia and communities should collaborate and these knowledge-sharing strategies be implemented in order for awareness and interventions to become more networked, inclusive, resilient and effective. Communities should be viewed as 'thought partners', who challenge conventional strategies and aid in developing innovative approaches to community resilience building.

Personal air pollutant exposure monitoring in South African children in the VHEMBE birth cohort.

The burden of disease associated with environmental exposures disproportionately impacts residents of low- and middle-income countries. Children living in rural regions of these countries may experience higher exposure to insecticides from indoor residual spraying used for malaria control and household air pollution. This study evaluated environmental exposures of children living in a rural region of South Africa. Quantifying exposure levels and identifying characteristics that are associated with exposure in this geographic region has been challenging due to limitations with available monitoring techniques. Wearable passive samplers have recently been shown to be a convenient and reliable tool for assessing personal exposures. In this study, a passive sampler wristband, known as Fresh Air wristband, was worn by 49 children (five-years of age) residing in the Limpopo province of South Africa. The study leveraged ongoing research within the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE) birth cohort. A wide range of chemicals (35 in total) were detected using the wristbands, including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, phthalates, and organophosphate esters (OPEs) flame retardants. Higher concentrations of PAHs were observed among children from households that fell below the food poverty threshold, did not have access to electric cookstoves/burners, or reported longer times of cooking or burning materials during the sampling period. Concentrations of p,p'-DDD and p,p'-DDT were also found to be elevated for children from households falling below the food poverty threshold as well as for children whose households were sprayed for malaria control within the previous 1.5 years. This study demonstrates the feasibility of using passive sampler wristbands as a non-invasive method for personal exposure assessment of children in rural regions of South Africa to complex mixtures environmental contaminants derived from a combination of sources. Future studies are needed to further identify and understand the effects of airborne environmental contaminants on childhood development and strategies to mitigate exposures.

Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology.

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers.

BACKGROUND: African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation. METHODS: Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (African versus European), with a focus on African men from southern Africa. RESULTS: Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion partners were identified, including LINC01525, FBXO7, GTF3C2, NTNG1 and YPEL5. Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, with CADM2, LSAMP, PTPRD, PDE4D and PACRG having therapeutic implications for African patients. CONCLUSIONS: In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry.

Maternal exposure to DDT, DDE, and pyrethroid insecticides for malaria vector control and hypospadias in the VHEMBE birth cohort study, Limpopo, South Africa.

Hypospadias is the ectopic opening of the urethra on the penis or scrotum. Exposure to estrogenic and/or anti-androgenic chemicals in utero may play an etiologic role. DDT and the pyrethroids cypermethrin and deltamethrin, are used to control malaria. DDT is estrogenic and its breakdown product DDE is anti-androgenic; cypermethrin and deltamethrin can also disrupt androgen pathways. We examined the relationship between maternal exposure to these insecticides during pregnancy and hypospadias among boys participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) in Limpopo Province, South Africa. We measured peripartum levels of p,p'-DDT and p,p'-DDE in maternal serum and urinary pyrethroid metabolites. We conducted urogenital examination on 359 one-year-old boys. A total of 291 (81.0 %) had phimosis, which prevented full urogenital examination, leaving a final sample of 68 boys for determination of the presence of hypospadias. Diagnosis was based on concordance of two independent physicians. We identified hypospadias in 23 of the 68 boys (34 %). Maternal urinary concentrations of cis-DCCA and trans-DCCA metabolites of cypermethrin and other pyrethroids, were associated with an increased risk for hypospadias, but the other metabolite 3-PBA was not (adjusted relative risk per 10-fold increase = 1.58, 95 % CI 1.07-2.34; 1.61, 95 % CI 1.09-2.36; and 1.48, 95 % CI 0.78-2.78, respectively). No associations were found between p,p'-DDT, p,p'-DDE, 3-PBA or cis-DBCA and hypospadias. We observed a high prevalence of hypospadias among boys without phymosis. Boys with higher prenatal exposure to pyrethroid insecticides were at higher risk of hypospadias. Our findings may have global implications given that pyrethroid insecticides are widely used for malaria control, in agriculture and for home use.

In-utero exposure to DDT and pyrethroids and child behavioral and emotional problems at 2 years of age in the VHEMBE cohort, South Africa.

BACKGROUND: Half the world's population is at risk for malaria. Indoor residual spraying (IRS) with insecticides has been effective in controlling malaria, yet the potential neurotoxicity of these insecticides is of concern, particularly for infants exposed in utero. OBJECTIVES: To determine the association of prenatal exposure to DDT/DDE and pyrethroid insecticides and behavioral/emotional problems in two-year-old children. METHODS: The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort in South Africa, measured concentrations of p,p'-DDT and p,p'-DDE in maternal serum and pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, and 3-PBA) in maternal urine collected during pregnancy. At 2 years, 683 mothers were interviewed about their children's behavior and emotional development, using the Child Behavior Checklist (CBCL). We examined associations between behavioral or emotional problems and biomarkers of prenatal insecticide exposure. RESULTS: Maternal serum p,p'-DDT concentrations were associated with heightened withdrawn behavior in 2-year olds, with a 0.24 increase in raw scores (95%CI = 0.00, 0.49) and a 12% increase (95%CI = 1.01, 1.23) in risk of being at or above the borderline-clinical level, per 10-fold increase in concentrations. Ten-fold increases in p,p'-DDT and p,p'-DDE were related to 30% (RR = 1.30; 95%CI = 1.01, 1.67) and 39% (RR = 1.39; 95%CI =1.01, 1.91) higher risks, respectively, for increased oppositional-defiant behavior. p,p'-DDE concentrations were also related to increased risk of ADHD-related problems (RR = 1.30; 95%CI = 0.98, 1.72). Maternal urinary concentrations of cis-DBCA and 3-PBA were associated with increased risk of externalizing behaviors (RR = 1.30; 95%CI = 1.05, 1.62; RR = 1.35, 95%CI = 1.03, 1.78 per 10-fold increase, respectively), with some evidence of an association between cis-DBCA and affective disorders (RR = 1.25; 95%CI = 0.99, 1.56). Some associations with maternal pyrethroid concentrations were stronger in girls than boys. CONCLUSIONS: Prenatal exposure to DDT and pyrethroid insecticides may be associated with maternally-reported behavioral problems in two-year-old children. Given their long history and continued use, further investigation is warranted.

Discriminatory Gleason grade group signatures of prostate cancer: An application of machine learning methods.

One of the most precise methods to detect prostate cancer is by evaluation of a stained biopsy by a pathologist under a microscope. Regions of the tissue are assessed and graded according to the observed histological pattern. However, this is not only laborious, but also relies on the experience of the pathologist and tends to suffer from the lack of reproducibility of biopsy outcomes across pathologists. As a result, computational approaches are being sought and machine learning has been gaining momentum in the prediction of the Gleason grade group. To date, machine learning literature has addressed this problem by using features from magnetic resonance imaging images, whole slide images, tissue microarrays, gene expression data, and clinical features. However, there is a gap with regards to predicting the Gleason grade group using DNA sequences as the only input source to the machine learning models. In this work, using whole genome sequence data from South African prostate cancer patients, an application of machine learning and biological experiments were combined to understand the challenges that are associated with the prediction of the Gleason grade group. A series of machine learning binary classifiers (XGBoost, LSTM, GRU, LR, RF) were created only relying on DNA sequences input features. All the models were not able to adequately discriminate between the DNA sequences of the studied Gleason grade groups (Gleason grade group 1 and 5). However, the models were further evaluated in the prediction of tumor DNA sequences from matched-normal DNA sequences, given DNA sequences as the only input source. In this new problem, the models performed acceptably better than before with the XGBoost model achieving the highest accuracy of 74 ± 01, F1 score of 79 ± 01, recall of 99 ± 0.0, and precision of 66 ± 0.1.

Occurrence of legacy and replacement plasticizers, bisphenols, and flame retardants in potable water in Montreal and South Africa.

The occurrence of thirty-nine contaminants including plasticizers, bisphenols, and flame retardants in potable water from Montreal and South Africa was analyzed to determine their presence and concentrations in different water sources. In Montreal, five bottled water (BW) brands and three drinking water treatment plants (DWTP) were included. In South Africa, water was sampled from one urban DWTP located in Pretoria, Gauteng, and one rural DWTP located in Vhembe, along with water from the same rural DWTP which had been stored in small and large plastic containers. A combination of legacy compounds, typically with proven toxic effects, and replacement compounds was investigated. Bisphenols, Dechlorane-602, Dechlorane-603, and s-dechlorane plus (s-DP) were not detected in any water samples, and a-dechlorane plus (a-DP) was only detected in one sample from Pretoria at a concentration of 1.09 ng/L. Lower brominated polybrominated diphenyl ethers (PBDE)s were detected more frequently than higher brominated PBDEs, always at low concentrations of <2 ng/L, and total PBDE levels were statistically higher in South Africa than in Montreal. Replacement flame retardants, organophosphate esters (OPEs), were detected at statistically higher concentrations in Montreal's BW (68.56 ng/L), drinking water (DW) (421.45 ng/L) and Vhembe (198.33 ng/L) than legacy PBDEs. Total OPE concentrations did not demonstrate any geographical trend; however, levels were statistically higher in Montreal's DW than Montreal's BW. Plasticizers were frequently detected in all samples, with legacy compounds DEHP, DBP, and replacement DINCH being detected in 100 % of samples with average concentrations ranging from 6.89 ng/L for DEHP in Pretoria to 175.04 ng/L for DINCH in Montreal's DW. Total plasticizer concentrations were higher in Montreal than in South Africa. The replacement plasticizers (DINCH, DINP, DIDA, and DEHA) were detected at similar frequencies and concentrations as legacy plasticizers (DEHP, DEP, DBP, MEHP). For the compounds reported in earlier studies, the concentrations detected in the present study were similar to other locations. These compounds are not currently regulated in drinking water but their frequent detection, especially OPEs and plasticizers, and the presence of replacement compounds at similar or higher levels than their legacy compounds demonstrate the importance of further investigating the prevalence and the ecological or human health effects of these compounds.

Prenatal exposure to insecticides and child cardiometabolic risk factors in the VHEMBE birth cohort.

As part of malaria control programs, many countries spray dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides inside dwellings in a practice called indoor residual spraying that results in high levels of exposure to local populations. Gestational exposure to these endocrine- and metabolism-disrupting chemicals may influence child cardiometabolic health. Methods: We measured the serum concentration of DDT and dichlorodiphenyldichloroethylene (DDE) and urinary concentration of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in peripartum samples collected between August 2012 and December 2013 from 637 women participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. We applied marginal structural models to estimate the relationship between biomarker concentrations and child-size (height and weight), adiposity (body mass index [BMI], body fat percentage, waist circumference) and blood pressure at 5 years of age. Results: Maternal concentrations of all four pyrethroid metabolites were associated with lower adiposity including reduced BMI z-scores, smaller waist circumferences, and decreased body fat percentages. Reductions in BMI z-score were observed only among children of mothers with sufficient energy intake during pregnancy (ßcis-DCCA, trans -DCCA=-0.4, 95% confidence interval (CI) = -0.7,-0.1; pinteraction=0.03 and 0.04, respectively) but there was no evidence of effect modification for the other measures of adiposity. Maternal p,p'-DDT concentrations were associated with a reduction in body fat percentage (ß = -0.4%, 95% CI = -0.8,-0.0). Conclusions: Gestational exposure to pyrethroids may reduce adiposity in children at 5 years of age.

Prenatal Exposure to Insecticides and Weight Trajectories Among South African Children in the VHEMBE Birth Cohort.

BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides are sprayed inside dwellings for malaria vector control, resulting in high exposure to millions of people, including pregnant women. These chemicals disrupt endocrine function and may affect child growth. To our knowledge, few studies have investigated the potential impact of prenatal exposure to DDT or pyrethroids on growth trajectories. METHODS: We investigated associations between gestational insecticide exposure and child growth trajectories in the Venda Health Examination of Mothers, Babies and their Environment, a birth cohort of 751 children born between 2012 and 2013 in South Africa. Based on child weight measured at follow-up and abstracted from medical records, we modeled weight trajectories from birth to 5 years using SuperImposition, Translation and Rotation, which estimated two child-specific parameters: size (average weight) and tempo (age at peak weight velocity). We estimated associations between peripartum maternal concentrations of serum DDT, dichlorodiphenyldichloroethylene, or urinary pyrethroid metabolites and SuperImposition, Translation and Rotation parameters using marginal structural models. RESULTS: We observed that a 10-fold increase in maternal concentrations of the pyrethroid metabolite trans-3-(2,2,-dicholorvinyl)-2,2-dimethyl-cyclopropane carboxylic acid was associated with a 21g (95% confidence interval = -40, -1.6) smaller size among boys but found no association among girls (Pinteraction = 0.07). Estimates suggested that pyrethroids may be associated with earlier tempo but were imprecise. We observed no association with serum DDT or dichlorodiphenyldichloroethylene. CONCLUSIONS: Inverse associations between pyrethroids and weight trajectory parameters among boys are consistent with hypothesized disruption of androgen pathways and with our previous research in this population, and support the endocrine-disrupting potential of pyrethroids in humans.

Targeted screening of 11 bisphenols and 7 plasticizers in food composites from Canada and South Africa.

A sensitive method based on ultrasound-assisted liquid extraction coupled with liquid chromatography was applied to screen 18 plastic-related contaminants in 168 food composites (namely fish fillets, chicken breast, canned tuna, leafy vegetables, bread and butter) collected in Montreal (Canada), Pretoria and Vhembe (South Africa). Bisphenol A (BPA), bisphenol S (BPS) and seven plasticizers (di-n-butyl phthalate (DBP), diethyl phthalate (DEP), (2-ethylhexyl) phthalate (DEHP), di-(2-ethylhexyl) adipate (DEHA), di-isononyl phthalate (DINP), di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH)) were detected in different foods from both countries. DBP and DEP were the most frequently detected contaminants in food collected in Montreal (75% for both) and DINP was the most frequently detected contaminant in food from South Africa (67%). DEHA concentration in packaged fish were significantly higher than the values for non-packaged fish (p < 0.01) suggesting that the packaging film can be one source of DEHA in fish.

Assessing the External Exposome Using Wearable Passive Samplers and High-Resolution Mass Spectrometry among South African Children Participating in the VHEMBE Study.

Children in low- and middle-income countries are often exposed to higher levels of chemicals and are more vulnerable to the health effects of air pollution. Little is known about the diversity, toxicity, and dynamics of airborne chemical exposures at the molecular level. We developed a workflow employing state-of-the-art wearable passive sampling technology coupled with high-resolution mass spectrometry to comprehensively measure 147 children's personal exposures to airborne chemicals in Limpopo, South Africa, as part of the Venda Health Examination of Mothers, Babies, and Their Environment (VHEMBE). 637 environmental exposures were detected, many of which have never been measured in this population; of these 50 airborne chemical exposures of concern were detected, including pesticides, plasticizers, organophosphates, dyes, combustion products, and perfumes. Biocides detected in wristbands included p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), propoxur, piperonyl butoxide, and triclosan. Exposures differed across the assessment period with 27% of detected chemicals observed to be either higher or lower in the wet or dry seasons.