There are extensive data on the toxicity of glyphosate (GLY) based herbicides (GBH), however the interpretation of some data (e.g. carcinogenic effect) are subject to controversy. For the appropriate ...health risk assessment more data on exposure levels in the general population, especially in susceptible groups such as pregnant women, the elderly and children are needed.
The aims of the present study were to estimate the exposure to GLY and its major metabolite aminomethylphosphonic acid (AMPA) in children and adolescents living in agricultural areas, to identify possible determinants of the exposure, and to assess co-exposure with elements. In total, 149 children (aged 7–10 years, 55% girls) and 97 adolescents (aged 12–15 years; 44% girls) were recruited in 2018 from rural areas of Northeastern Slovenia. The effect of seasonal GLY application on the exposure was estimated using GLY and AMPA levels determined by GC–MS/MS in first morning urine in winter (n = 246) and in late-spring/early-summer seasons (n = 225). Levels of elements were determined by ICP-MS in urine in both samplings and in blood or plasma in the first sampling. Questionnaire data on basic characteristics, dietary habits, living environments and use of pesticides were obtained for all participants.
GLY and AMPA were detected in 27% and 50% of urine samples from the first sampling period, respectively; and in 22% and 56% from the second sampling period, respectively. Geometric means and medians of both AMPA and GLY were below or at the limit of quantification (≤LOQ; 0.1 µg/L). Children rather than adolescents tended to have higher exposure, as did, boys rather than girls among adolescents. The exposure did not significantly differ between both sampling periods. Except for one individual, exposure was not higher among participants who reported use of GLY or herbicides in the vicinity of child’s home or live in close vicinity of agriculture, orchards, vineyards, gardens, sport courts or cemeteries. The extensive food consumption frequency data revealed higher exposure to GLY and AMPA only among individuals with higher consumption of nuts and wholegrain rice. Levels of AMPA and GLY were significantly positively correlated, with considerably stronger correlation in urine of the second than the first sampling (Spearman’s rank coefficient: 0.49 vs 0.22, respectively). Urine levels of As, Pb, Co, Zn and Cu were significantly higher in participants with GLY and/or AMPA levels ≥LOQ than with levels <LOQ.
In conclusion, this first estimation of GLY and AMPA exposure in a Slovenian study population showed much lower levels when compared to levels reported in similar studies worldwide. Some results might be explained by more intensive use of GBH in spring, but in general we were unable to distinguish between exposure from the diet or use of GBH in residential environments.
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•Children and adolescents from Slovenia are exposed to a variety of endocrine disruptors.•Exposure to bisphenol A and triclosan is lower than the human biomonitoring (HBM) reference ...values.•Urinary bisphenol A levels are associated with consumption of high fat foods.•Urinary levels of methyl paraben are associated with use of cosmetic products.•UGT2B15 associated with susceptibility to adverse effects of methyl and ethyl paraben.
Chemicals such as bisphenols, parabens and triclosan are endocrine disrupting chemicals. They are used in a wide variety of consumer products, making human exposure to those chemicals widespread.
In the present study, levels of three bisphenols (bisphenol A, F and S), 7 parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl-, butyl-, benzyl paraben) and triclosan were measured in first morning void from 246 Slovenian children and adolescents, aged 6–9 and 11–15 years and living in a rural region of Slovenia. Median levels of specific-gravity corrected levels for bisphenol A, bisphenol F, methyl paraben and ethyl paraben were 1.9, 0.085, 5.4 and 2.5 µg/L for children and 1.6, 0.11, 7.2 and 6.0 µg/L for adolescents, respectively. Median levels for all other endocrine disrupting chemicals were < LOQ. The levels are comparable with the levels reported in studies across the world. Exposure was age, sex, and location specific. Higher levels of bisphenol F and ethyl paraben were found in the samples of adolescents, while higher levels of methyl paraben were found in samples from girls. Furthermore, individuals living in one of the sampling locations, Goričko, were exposed to higher levels of bisphenol F and ethyl paraben than those in the remaining two sampling locations. Information about participants’ dietary habits, use of food packaging and personal care products was obtained through questionnaires, and used to investigate associations between urinary levels of the biomarkers and potential exposure sources. High fat foods were associated with bisphenol A exposure, and cosmetics items such as lipstick and perfume with methyl paraben exposure. Significant correlation between methyl- and propyl paraben was observed in children’s samples, suggesting similar exposure sources, while other compounds were not largely correlated, indicating independent sources. Furthermore, association between a single nucleotide polymorphism (SNP) in UGT2B15 gene and urinary levels of methyl and ethyl paraben was observed, showing the role of UGT2B15 isoform in methyl and ethyl paraben metabolism as well as indicating the SNP rs1902023 as a potential biomarker of susceptibility to adverse effects caused by the exposure.
The present study reports exposure of children and adolescents in Slovenia to a wide range of different endocrine disrupting chemicals for the first time, connecting it to exposure patterns and exposure sources. The study is to the authors’ knowledge the first that investigates direct connection between levels of urinary endocrine disrupting chemical biomarkers and genetic polymorphism in UGT2B15.
Phthalates and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), bisphenols (BPs), parabens (PBs), and triclosan (TCS) are high-production-volume chemicals of pseudo-persistence that are ...concerning for the environment and human health. This study aims to assess the exposure to 10 phthalates, DINCH, and environmental phenols (3 BPs, 7 PBs, and TCS) of Slovenian men (n = 548) and lactating primiparous women (n = 536). We observed urinary concentrations comparable to studies from other countries and significant differences among the sub-populations. In our study, men had significantly higher levels of phthalates, DINCH, and BPs, whereas the concentrations of PBs in urine were significantly higher in women. The most significant determinant of exposure was the area of residence and the year of sampling (2008–2014) that mirrors trends in the market. Participants from urban or industrialized sampling locations had higher levels of almost all monitored analytes compared to rural locations. In an attempt to assess the risk of the population, hazard quotient (HQ) values were calculated for individual compounds and the chemical mixture. Individual analytes do not seem to pose a risk to the studied population at current exposure levels, whereas the HQ value of the chemical mixture is near the threshold of 1 which would indicate a higher risk. We conclude that greater emphasis on the risk resulting from cumulative exposure to chemical mixtures and additional studies are needed to estimate the exposure of susceptible populations, such as children.
•Endocrine disrupting chemicals were detected at high frequencies.•Concentrations were low compared to the literature.•The combined hazard quotient is near 1.•Concentrations of phthalates and phenols are decreasing between 2008 and 2014.•Concentrations of DINCH are increasing between 2008 and 2014.
•Pesticides were analysed in the urine of Slovenian mothers and their 7 year-old children.•The concentrations of most OPs and PYRs were higher in children than in their mothers.•The concentrations of ...most OPs and PYRs in mothers and children were correlated.•The parathion metabolite was the one in highest concentration in mothers and children.•The estimated daily intakes of OPs and PYRs did not show adverse health effect risks.
The present study reports one of the few cases in which organophosphate (OP) and pyrethroid (PYR) pesticide human exposure is evaluated in family contexts by the analysis of mother/child pair samples. Urinary concentrations of 6 organic metabolites of organophosphates and 2 pyrethroids were measured in mothers and their 7-to 8-year-old children (n = 168) in a general population from the central area of Slovenia. The results were adjusted for specific gravity and creatinine.
The most abundant OP metabolite in children was 4-nitrophenol (PNP) (median 0.7 ng/ml) and in mothers (0.45 ng/ml), representing parathion exposure. 3-Phenoxibenzoic acid (3-PBA) (0.26 ng/ml), the general metabolite of pyrethroids, and 3,5,6-trichloro-2-pyridinol (TCPY) (0.16 ng/ml; chlorpyriphos) were the second most abundant compounds in children and mothers, respectively. The geometric mean specific gravity adjusted concentrations of OPs and PYRs were statistically significantly higher in children than in their mothers (between 3% and 24% higher), with the exception of TCPY (26% lower). All OP and PYR metabolites found in higher concentration in children showed significant positive correlations with the metabolite concentrations found in the mothers (p < 0.05 and 0.01), involving the fact that higher maternal concentrations were associated with higher children levels.
These differential mother-children distributions and significant correlations were observed for the 2 types of pesticides studied, OPs and PYRs, which have different chemical properties. This agreement is consistent with the incorporation of the pesticides because of the general activities developed in the family context, instead of pesticide-dependent specific inputs.
Comparison of the estimated daily intakes with the acceptable daily intakes of all detected metabolites revealed no significant risk of adverse health effects from exposure to these pesticides.
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Single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYPs) and UDP-glucuronosyltransferase (UGTs) genes have been proposed to influence phthalates and ...1,2-cyclo-hexanedicarboxylic acid diisononyl ester (DINCH) biotransformation but have not been investigated on a populational level.
We investigated the role of SNPs in CYP2C9, CYP2C19, CYP2D6, UGT2B15, and UGT1A7 genes in the biotransformation of phthalates (DEHP, DEP, DiBP, DnBP, BBzP, DiNP, DidP) and DINCH by determining their urine metabolites.
From the Slovenian study population of 274 men and 289 lactating primiparous women we obtained data on phthalate and DINCH urine metabolite levels (MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, MEP, MiBP, MnBP, MBzP, cx-MINP, OH-MiDP, MCHP, MnPeP, MnOP, 5OH-MINCH, 5oxo-MINCH), SNP genotypes (rs1057910 = CYP2C9*3, rs1799853 = CYP2C9*2, rs4244285 = CYP2C19*2, rs12248560 = CYP2C19*17, rs3892097 = CYP2D6*4, rs1902023 = UGT2B15*2, and rs11692021 = UGT1A7*3) and questionnaires. Associations of SNPs with levels of metabolites and their ratios were assessed by multiple linear regression and ordinary logistic regression analyses.
Significant associations were observed for CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs. The most pronounced was the influence of CYP2C9*2 and *3 on the reduced DEHP biotransformation, with lower levels of metabolites and their ratios in men and women. In contrast, carriers of CYP2C19*17 showed higher urine levels of DEHP metabolites in both genders, and in women also in higher DiNP, DiDP, and DINCH metabolite levels. The presence of UGT1A7*3 was associated with increased metabolite levels of DINCH in men and of DiBP and DBzP in women. Statistical models explained up to 27% of variability in metabolite levels or their ratios.
Our observations confirm the effect of CYP2C9*2 and *3 SNPs towards reduced DEHP biotransformation. We show that CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs might represent biomarkers of susceptibility or resilience in phthalates and DINCH exposure that have been so far unrecognised.
The European Union's 7th Framework Programme (EU's FP7) project HEALS – Health and Environment-wide Associations based on Large Population Surveys – aims a refinement of the methodology to elucidate ...the human exposome. Human biomonitoring (HBM) provides a valuable tool for understanding the magnitude of human exposure from all pathways and sources. However, availability of specific biomarkers of exposure (BoE) is limited.
The objective was to summarize the availability of BoEs for a broad range of environmental stressors and exposure determinants and corresponding reference and exposure limit values and biomonitoring equivalents useful for unraveling the exposome using the framework of environment-wide association studies (EWAS).
In a face-to-face group discussion, scope, content, and structure of the HEALS deliverable “Guidelines for appropriate BoE selection for EWAS studies” were determined. An expert-driven, distributed, narrative review process involving around 30 individuals of the HEALS consortium made it possible to include extensive information targeted towards the specific characteristics of various environmental stressors and exposure determinants. From the resulting 265 page report, targeted information about BoE, corresponding reference values (e.g., 95th percentile or measures of central tendency), exposure limit values (e.g., the German HBM I and II values) and biomonitoring equivalents (BEs) were summarized and updated.
64 individual biological, chemical, physical, psychological and social environmental stressors or exposure determinants were included to fulfil the requirements of EWAS. The list of available BoEs is extensive with a number of 135; however, 12 of the stressors and exposure determinants considered do not leave any measurable specific substance in accessible body specimens. Opportunities to estimate the internal exposure stressors not (yet) detectable in human specimens were discussed.
Data about internal exposures are useful to decode the exposome. The paper provides extensive information for EWAS. Information included serves as a guideline – snapshot in time without any claim to comprehensiveness – to interpret HBM data and offers opportunities to collect information about the internal exposure of stressors if no specific BoE is available.
Mercury is a neurotoxin, and limited prenatal exposure to it can affect long-term child neurodevelopment. However, results of epidemiologic studies of such exposure have been inconsistent. We ...examined the association of prenatal mercury exposure from maternal fish consumption with child neurodevelopment in northern Italy.
A population-based cohort of 606 children and their mothers was studied from pregnancy to age 18 months. Mercury levels were measured in maternal hair and blood during pregnancy and in umbilical cord blood and breast milk. Levels of polyunsaturated fatty acids (PUFAs) were measured in maternal serum. Maternal and child intakes of fish were assessed by using a food frequency questionnaire. The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was used to evaluate child neurodevelopment. Multivariate linear regression was used to examine the association of mercury exposure with BSID-III scores, after controlling for maternal fish intake, PUFAs during pregnancy, and several other confounders.
Mean weekly fish intake during pregnancy was less than 2 servings. Mercury concentrations in biological samples were low (mean, 1061 ng/g in hair) and moderately correlated with fish intake, particularly of carnivorous species. Maternal ω-3 PUFA concentrations were poorly correlated with fish intake. Maternal intelligence quotient (IQ) and child intake of fish were significantly associated with neurodevelopment scores. In multivariate models, the level of Hg exposure was not associated with neurodevelopmental performance at 18 months.
In this Italian population, neurodevelopment at 18 months was associated with child intake of fresh fish and maternal IQ rather than with mercury exposure. The expected beneficial effect of maternal fish intake (from maternal ω-3 PUFAs) was not found.
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•17% and 20% APOE ε4 carriers were identified among mothers and new-borns.•Mothers carrying APOE ε4 had higher Hg, As in venous and cord blood.•Mothers carrying APOE ε4 allele had ...higher Se in venous blood and plasma.•Statistical models confirmed maternal APOE ε4 and venous plasma Se association.•Seafood, ever-smoking, and parity had strong influence on studied associations.
We investigated the relationship between lipid binding glycoprotein apolipoprotein E (apoE; gene APOE) polymorphisms (ε4 allele carriers versus no carriers = ε4+/ε4−) and trace elements (TEs) (e.g., (methyl)mercury, arsenic, lead, cadmium, selenium, manganese, copper, and zinc) in mothers (N = 223) and their new-borns (N = 213) exposed to potentially toxic metal(loid)s from seafood consumption. The apoE isoform encoded by the ε4 allele is believed to have beneficial effects in early life but represents a risk factor for age-associated diseases. Under certain conditions ε4 carriers are more susceptible to oxidative stress and metal(loid) toxicity. DNA from Croatian pregnant women (N = 223, third trimester) and their new-borns (N = 176), was genotyped for APOE by TaqMan® SNP assay – rs429358 and rs7412. Seafood intake data and TE levels in maternal urine, milk, hair, peripheral venous blood, mixed cord blood, and new-borns’ urine were available from previous studies. We compared TEs between ε4+ and ε4− carriers using Mann-Whitney U tests and applied multiple linear regression models to analyse the TE’s dependence on the presence of allele ε4 (genotypes ε3/ε4, ε4/ε4) in combination with other explanatory variables. We identified 17% (n = 37) and 20% (n = 35) ε4 allele carriers in mothers and new-borns, respectively. The Mann-Whitney U test showed that mothers with the ε4 allele had significantly higher mean levels of (methyl)mercury in peripheral venous blood, cord blood, and hair; arsenic in urine and cord blood; and selenium in peripheral venous blood and plasma. However, taking confounders into account, only the maternal plasma selenium remained statistically significant in the linear regression models (ε4 carriers vs non-carriers: 62.6 vs 54.9 ng/mL, p < 0.001). Literature suggestions of possible ε4 allele impact on Hg levels were not observed, while superior selenium status observed in healthy pregnant women carrying allele ε4 could be linked to the proposed APOE ε4 beneficial effects early in life.
For reason beyond the control of the authors or the editors, the article titled “Colloidal Organic Matter and Metal(loid)s in Coastal Waters (Gulf of Trieste, Northern Adriatic Sea)” by Katja Klun1 · ...Ingrid Falnoga2 · Darja Mazej2 · Primož Šket3 · Jadran Faganeli1 (
https://doi.org/10.1007/s10498-019-09359-6
) was published in the regular issue Vol. 25 issue 5-6 instead of this special section, where it was originally scheduled to appear. Therefore, the full article is reprinted here.
Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question ...about “safety” of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue.
The Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores, obtaining adjusted β coefficients and odds ratios (ORs). These values were used to conduct a meta-analysis, to explore possible heterogeneity among countries and to obtain combined estimates of the association between THg exposure and BSID-III scores.
Median THg (ng/g) was: 704 in maternal hair, 2.4 in maternal blood, 3.6 in cord blood, and 0.6 in breast milk. THg concentrations were highest in Greece and lowest in Slovenia. BSID-III neurodevelopmental scores were higher in Croatia and Slovenia. The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair (n = 1086; β = 0.55; 95%CI: 0.05–1.05 and n = 1075; β = 0.12; 95%CI: 0.02–0.22, respectively). The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant (n = 882; OR = 1.03; 95%CI: 1.00–1.07). Heterogeneity was found across the four sub-cohorts for language composite score in maternal blood, and for fine motor scaled score in cord blood and breast milk. Language composite score and THg concentrations in maternal venous blood were positively related (n = 58; β = 4.29; CI95% (−0.02, 8.60)) in Croatia and an increase of 1 ng/g of THg in maternal venous blood was associated with a reduced risk for children to fall in the lowest quintile of language score by 31% (n = 58; OR = 0.69; CI 95%: 0.37, 1.01). The comparison of β coefficients obtained by multiple linear regression model showed an inverse association between fine motor score and THg concentrations in cord blood for Croatia (n = 54; β = −0.53; CI 95%: −1.10, 0.04) and Slovenia (n = 225; β = −0.25; CI 95%: −0.49, −0.01). In Slovenia THg level in breast milk was associated with suboptimal fine motor performance (n = 195; OR = 5.25; CI 95%: 1.36, 21.10).
This study showed an inverse relation between THg levels and developmental motor scores at 18 months, although the evidence was weak and partially internally and externally inconsistent. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age.
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