Toxicokinetics of dioxins and other organochlorine compounds in Japanese people: Association with hepatic CYP1A2 expression levels

Concentrations of persistent organochlorine compounds (OCs) including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in the liver and adipose tissue of Japanese cadavers were measured, and their toxicokinetics were examined in association with hepatic cytochrome P450 (CYP) 1A protein expression levels. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were 66 ± 74 and 65 ± 57 pg/g lipid weight (mean ± S.D.) in the liver and adipose tissue, respectively. Total PCBs (sum of 62 congeners targeted), p,p′-dichlorodiphenyl-dichloroethylene (p,p′-DDE) and β-hexachlorocyclohexane (β-HCH) were detected at concentrations over 1 μg/g lipid in both tissues of some specimens. For most of the dioxin-like congeners, total PCBs, p,p′-DDE, oxychlordane, α- and β-HCH, hexachlorobenzene (HCB), and tris(4-chlorophenyl)methane (TCPMe), age-dependent increases in concentrations were found in the adipose tissue of males. No such age-dependent trend was observed in the liver, suggesting that there are different mechanisms underlying the hepatic concentrations of OCs. Immunoblot analyses indicated detectable expression of hepatic CYP1A2 protein, whereas no CYP1A1 protein was detected. The CYP1A2 expression levels were positively correlated with concentrations (on wet weight basis) of 2,3,4,7,8-P₅CDF, the dominant TEQ-contributed congeners in the liver, indicating the induction of this CYP. Hepatic CYP1A2 protein levels were strongly correlated with the liver to adipose concentration (L/A) ratios of PCDD/F congeners with more than 5 chlorine atoms. Together with higher concentrations of the congeners in the liver than in the adipose tissue, the observation on L/A ratios of highly chlorinated PCDD/Fs suggests that induced hepatic CYP1A2 protein is involved in their sequestration in this human population, as observed in model animals (rodents). Nonetheless, the magnitude of hepatic sequestration (L/A ratio) of PCDD/Fs in this human population was lower than in other mammals and birds, reported previously. This study emphasizes the fact that toxicokinetics of some OCs can be affected at least partly by CYP1A2 protein levels in humans. For the extrapolation of their toxicokinetics from model animals to humans, knowledge on the induction and sequestration potencies of CYP1A is necessary.     

Particulate matter and early childhood body weight

Concerns over adverse effects of air pollution on children's health have been rapidly rising. However, the effects of air pollution on childhood growth remain to be poorly studied. We investigated the association between prenatal and postnatal exposure to PM10 and children's weight from birth to 60 months of age. This birth cohort study evaluated 1129 mother-child pairs in South Korea. Children's weight was measured at birth and at six, 12, 24, 36, and 60 months. The average levels of children's exposure to particulate matter up to 10 μm in diameter (PM10) were estimated during pregnancy and during the period between each visit until 60 months of age. Exposure to PM10 during pregnancy lowered children's weight at 12 months. PM10 exposure from seven to 12 months negatively affected weight at 12, 36, and 60 months. Repeated measures of PM10 and weight from 12 to 60 months revealed a negative association between postnatal exposure to PM10 and children's weight. Children continuously exposed to a high level of PM10 (> 50 μg/m³) from pregnancy to 24 months of age had weight z-scores of 60 that were 0.44 times lower than in children constantly exposed to a lower level of PM10 (≤ 50 μg/m³) for the same period. Furthermore, growth was more vulnerable to PM10 exposure in children with birth weight < 3.3 kg than in children with birth weight > 3.3 kg. Air pollution may delay growth in early childhood and exposure to air pollution may be more harmful to children when their birth weight is low.     

Biomarkers of pesticide exposure and diabetes in the 1999–2004 National Health and Nutrition Examination Survey

The associations of 8 pesticides and pesticide metabolites with total diabetes (diagnosed and undiagnosed) and pre-diabetes (glycohemoglobin 5.7–6.4%) were evaluated using the National Health and Nutrition Examination Survey (NHANES), 1999–2004. Six of the pesticides were found to be associated with total diabetes in separate adjusted logistic regressions. These pesticides and pesticide metabolites were beta-hexachlorocyclohexane, p,p′-DDE, p,p′-DDT, oxychlordane, trans-nonachlor, and heptachlor epoxide. When the number of compounds elevated was tested, 4 or more, of the 6, elevated had an odds ratio of 4.99 (95% CI 1.97–12.61) compared to none elevated. When the 6 compounds were tested together in a single combined adjusted logistic regression only oxychlordane, a metabolite of chlordane, and heptachlor epoxide, a metabolite of heptachlor, were significantly associated with total diabetes. In the combined adjusted logistic regression, oxychlordane ≥ 14.5 ng/g lipid adjusted had an odds ratios of 1.90 (95% CI 1.09–3.32) compared to oxychlordane < 14.5 ng/g lipid adjusted, and heptachlor epoxide ≥ 14.6 ng/g lipid adjusted had an odds ratio of 1.70 (95% CI 1.16–2.49) compared to heptachlor epoxide < 14.6 ng/g lipid adjusted. Heptachlor epoxide and p,p′-DDT were significantly associated with pre-diabetes in separate adjusted logistic regressions. When these 2 compounds were tested together only heptachlor epoxide remained significantly associated with pre-diabetes. The evidence supporting the relationship between pesticides and pesticide metabolites, with diabetes, was strongest for heptachlor epoxide and oxychlordane, intermediate for p,p′-DDT, and least for beta-hexachlorocyclohexane, p,p′-DDE, and trans-nonachlor. Mirex and dieldrin were not associated with total diabetes or pre-diabetes.     

Association between maternal exposure to perfluorooctanoic acid (PFOA) from electronic waste recycling and neonatal health outcomes

ObjectivePerfluorooctanoic acid (PFOA) has applications in numerous industrial and consumer products. The widespread prevalence of PFOA in humans demonstrated in recent studies has drawn considerable interest from the public. We aimed to evaluate the exposure of mothers to PFOA and the potential hazards to neonates in a primitive electronic waste recycling area, Guiyu, China, and a control area, Chaonan, China.MethodsOur investigation included analyses of maternal serum samples, health effect examinations, and other relevant factors. Questionnaires were administered and maternal serum samples were collected for 167 pregnant women. Solid phase extraction method was used for all analytical sample preparation, and analyses were completed using high performance liquid chromatography tandem mass spectrometry method.ResultsThe PFOA concentration was higher in maternal serum samples from Guiyu than in samples from Chaonan (median 16.95, range 5.5–58.5 ng mL^− 1; vs. 8.7, range 4.4–30.0 ng mL^− 1; P < 0.001). Residence in Guiyu, involvement in e-waste recycling, husband's involvement in e-waste and use of the family residence as workshop were significant factors contributing to PFOA exposure. Maternal PFOA concentrations were significantly different between normal births and adverse birth outcomes including premature delivery, term low birth weight, and stillbirths. After adjusting for potential confounders, PFOA was negatively associated with gestational age [per lg-unit: β = − 15.99 days, 95% confidence interval (CI), − 27.72 to − 4.25], birth weight (per lg-unit: β = − 267.3 g, 95% CI, − 573.27 to − 37.18), birth length (per lg-unit: β = − 1.91 cm, 95% CI, − 3.31 to − 0.52), and Apgar scores (per lg-unit: β = − 1.37, 95% CI, − 2.42 to − 0.32), but not associated with ponderal index.ConclusionsMothers from Guiyu were exposed to higher levels of PFOA than those from control areas. Prenatal exposure to PFOA was associated with decreased neonatal physical development and adverse birth outcomes.     

Boron exposure through drinking water during pregnancy and birth size

BackgroundBoron is a metalloid found at highly varying concentrations in soil and water. Experimental data indicate that boron is a developmental toxicant, but the few human toxicity data available concern mostly male reproduction.ObjectivesTo evaluate potential effects of boron exposure through drinking water on pregnancy outcomes.MethodsIn a mother-child cohort in northern Argentina (n = 194), 1–3 samples of serum, whole blood and urine were collected per woman during pregnancy and analyzed for boron and other elements to which exposure occurred, using inductively coupled plasma mass spectrometry. Infant weight, length and head circumference were measured at birth.ResultsDrinking water boron ranged 377–10,929 μg/L. The serum boron concentrations during pregnancy ranged 0.73–605 μg/L (median 133 μg/L) and correlated strongly with whole-blood and urinary boron, and, to a lesser extent, with water boron. In multivariable-adjusted linear spline regression analysis (non-linear association), we found that serum boron concentrations above 80 μg/L were inversely associated with birth length (B − 0.69 cm, 95% CI − 1.4; − 0.024, p = 0.043, per 100 μg/L increase in serum boron). The impact of boron appeared stronger when we restricted the exposure to the third trimester, when the serum boron concentrations were the highest (0.73–447 μg/L). An increase in serum boron of 100 μg/L in the third trimester corresponded to 0.9 cm shorter and 120 g lighter newborns (p = 0.001 and 0.021, respectively).ConclusionsConsidering that elevated boron concentrations in drinking water are common in many areas of the world, although more screening is warranted, our novel findings warrant additional research on early-life exposure in other populations.     

Distribution of persistent organic pollutants in serum,omental, and parietal adipose tissue of French women with deep infiltrating endometriosis and circulating versus stored ratio as new marker of exposure

Several studies have assessed the potential role of environmental chemicals in the onset, growth, and/or physiopathology of endometriosis. However, their contour in terms of considered exposure markers remains limited. The present study aimed to characterize the internal exposure levels of 78 persistent organic pollutants (POPs, including dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides) in a set of 113 adult French women (45 controls, 68 cases), and to characterize the distribution of these POPs within three biological compartments (omental adipose tissue, parietal adipose tissue, and serum). For all targeted substances, the correlation between the concentrations measured in omental versus parietal adipose tissue was found strongly significant (p < 0.0001). An equivalence of the measures performed in parietal and omental adipose tissue was moreover observed with median levels of 6.4 vs. 7.4 pg/g l.w. for WHO-TEQ₂₀₀₅ PCDD/F, 4.5 vs. 4.7 pg/g l.w. for WHO-TEQ₂₀₀₅ dl-PCB, 137.1 vs. 147.9 ng/g l.w. for sum of 6 ndl-PCB, and 2.1 vs. 2.0 ng/g l.w. for sum of 7 i-PBDE, respectively. The same observation was made for individual targeted OCs compounds. Significant correlations were also observed between these concentrations determined in adipose tissue and those measured in serum for dioxins (WHO-TEQ₂₀₀₅ PCDD/F = 6.1 pg/g l.w), PCBs (WHO-TEQ₂₀₀₅ dl-PCB = 3.6 pg/g l.w., sum of 6 ndl-PCB = 81.1 ng/g l.w.), and brominated flame-retardants (sum of 7 i-PBDE = 0.9 ng/g l.w.). The circulating versus stored ratio of some exposure markers (Sum PCDDs, 1,2,3,6,7,8-HxCDF, slightly versus highly chlorinated PCBs ratio, PBDE 99 and PBB 153) was found statistically different for control and case individuals. These extended exposure data from deep infiltrating endometriosis patients are the first ones available for France and give a new insight about the equilibrium of chemicals between storage and circulating compartments that should be further considered as new marker of exposure in the context of exposure-health relationship studies.     

Comparing human exposure to emerging and legacy flame retardants from the indoor environment and diet with concentrations measured in serum

This study investigates associations between serum concentrations of emerging and legacy halogenated flame retardants (HFRs) in 46 Norwegian women and measured indoor air and dust concentrations of the HFRs as well as detailed information on diet and household factors. Hexabromobenzene (median 0.03 ng/g lipid) and Dechlorane 602 (median 0.18 ng/g lipid) were detected in about 50% of the samples and Dechlorane Plus syn (median 0.45 ng/g lipid) and anti (median 0.85 ng/g lipid) in more than 78%. The most abundant polybrominated diphenyl ethers were 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE-153; median 0.82 ng/g lipid) and 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47; median 0.49 ng/g lipid) detected in more than 70% of the samples. In the bivariate analysis, no consistent associations were observed between the biomonitoring data and measured concentrations in indoor air and dust. On the other hand, consumption of specific food items (mainly lamb/mutton and margarine) correlated significantly with more than two HFR serum concentrations, while this was not the case for household factors (electronic appliances). Only the significant bivariate associations with diet were confirmed by multivariate linear regression analyses, which might indicate a higher contribution from food compared to the indoor environment to the variation of the body burden of these HFRs.     

Tobacco smoke increases the risk of otitis media among Greenlandic Inuit children while exposure to organochlorines remain insignificant

BackgroundPrenatal exposure to environmental levels of organochlorines (OCs) has been demonstrated to have immunotoxic effects in humans. We investigated the relationship between prenatal exposure to OCs and the occurrence of otitis media (OM) among Inuit children in Greenland.MethodsWe estimated the concentration of 14 PCB congeners and 11 pesticides in maternal and cord blood samples and in breast milk in a population-based cohort of 400 mother–child pairs. At follow-up, we examined the children's ears and used their medical records to assess the OM occurrence and severity. Multivariate regression analyses were used with adjustments for passive smoking, crowding, dietary habits, parent's educational level, breast feeding and the use of child-care.ResultsThe children were 4–10 years of age at follow-up and 223 (85%) participated. We found no association between prenatal OC exposure and the development of OM. Factors associated with the child's hazard of OM during the first 4 years of life were: mother's history of OM (HR 1.70, 95% CI 1.11–2.59, p = 0.01); mother's smoking habits: current (HR 2.47, 95% CI 1.45–4.21, p < 0.01) and previous (HR 2.00, 95% CI 1.19–3.36, p < 0.01); number of smokers in the home (HR 1.17, 95% CI 1.05–1.31, p < 0.01). After adjustment mothers' smoking habits remained significant.ConclusionWe found no relationship between high levels of prenatal exposure of OCs and occurrence of OM. Passive smoking was found as the strongest environmental risk factor for the development of OM.Interventions to reduce passive smoke in children's environment are needed.     

Baseline blood trihalomethanes,semen parameters and serum total testosterone: A cross-sectional study in China

Toxicological studies showed that trihalomethanes (THMs), the most abundant classes of disinfection by-products (DBPs) in drinking water, impaired male reproductive health, but epidemiological evidence is limited and inconsistent. This study aimed to examine the associations of baseline blood THMs with semen parameters and serum total testosterone in a Chinese population. We recruited 401 men seeking semen examination from the Reproductive Center of Tongji Hospital in Wuhan, China between April 2011 and May 2012. Baseline blood concentrations of THMs, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were measured using SPME-GC/ECD method. Semen quality and serum total testosterone were analyzed. Multivariable linear regressions were used to assess the associations of baseline blood THM concentrations with semen parameters and serum total testosterone levels. We found that baseline blood THM concentrations were not associated with decrements in sperm motility, sperm straight-line and curvilinear velocity. However, moderate levels of BDCM (β = − 0.13 million; 95% CI: − 0.22, − 0.03) and DBCM (β = − 4.74%; 95% CI: − 8.07, − 1.42) were associated with decreased sperm count and declined sperm linearity compared with low levels, respectively. Suggestive dose–response relationships were also observed between elevated blood TCM or ∑ THMs (sum of TCM, BDCM, DBCM and TBM) concentration and decreased sperm concentration (both p for trend = 0.07), and between elevated blood DBCM concentration and decreased serum total testosterone (p for trend = 0.07). Our results indicate that elevated THM exposure may lead to decreased sperm concentration and serum total testosterone. However, the effects of THM exposure on male reproductive health still warrant further studies in humans.     

Correcting serum concentrations of organochlorine compounds by lipids: Alternatives to the organochlorine/total lipids ratio

IntroductionWhen studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction.MethodsIncident cases of PDA were interviewed and had blood drawn soon around hospital admission (n = 144). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection.ResultsMost patients with high TL had moderate or low concentrations of OCs. By contrast, the variability of OC values among patients with normal TL was large. Correlations were of a similar magnitude between OC and TL and between OC and total cholesterol; while these correlations were weak (all Spearman's ρ < 0.3 and R² < 0.11), no OC were significantly correlated with triglycerides. Although all alternatives to the OC/TL linear ratio were statistically significant for at least one OC, their R² was always below 10%.ConclusionsIn patients with severe diseases as PDA, linear correction of OC by TL as commonly performed in epidemiologic studies may be inappropriate. Results contribute to the scant literature on the rationale to correct serum concentrations of OC by lipids. They suggest that it is unwarranted to routinely correct OC by TL, offer ways to assess such need, and present alternatives as no TL correction, correction by total cholesterol only or use of different statistical models.     

Dietary benzo(a)pyrene intake during pregnancy and birth weight: Associations modified by vitamin C intakes in the Norwegian Mother and Child Cohort Study (MoBa)

BackgroundMaternal exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancy has been associated with reduced fetal growth. However, the role of diet, the main source of PAH exposure among non-smokers, remains uncertain.ObjectiveTo assess associations between maternal exposure to dietary intake of the genotoxic PAH benzo(a)pyrene [B(a)P] during pregnancy and birth weight, exploring potential effect modification by dietary intakes of vitamins C, E and A, hypothesized to influence PAH metabolism.MethodsThis study included 50,651 women in the Norwegian Mother and Child Cohort Study (MoBa). Dietary B(a)P and nutrient intakes were estimated based on total consumption obtained from a food frequency questionnaire (FFQ) and estimated based on food composition data. Data on infant birth weight were obtained from the Medical Birth Registry of Norway (MBRN). Multivariate regression was used to assess associations between dietary B(a)P and birth weight, evaluating potential interactions with candidate nutrients.ResultsThe multivariate-adjusted coefficient (95%CI) for birth weight associated with maternal energy-adjusted B(a)P intake was − 20.5 g (− 31.1, − 10.0) in women in the third compared with the first tertile of B(a)P intake. Results were similar after excluding smokers. Significant interactions were found between elevated intakes of vitamin C (> 85 mg/day) and dietary B(a)P during pregnancy for birth weight (P < 0.05), but no interactions were found with other vitamins. The multivariate-adjusted coefficients (95%CI) for birth weight in women in the third compared with the first tertile of B(a)P intake were − 44.4 g (− 76.5, − 12.3) in the group with low vitamin C intakes vs. − 17.6 g (− 29.0, − 6.1) in the high vitamin C intake group.ConclusionThe results suggest that higher prenatal exposure to dietary B(a)P may reduce birth weight. Lowering maternal intake of B(a)P and increasing dietary vitamin C intake during pregnancy may help to reduce any adverse effects of B(a)P on birth weight.     

Health burdens of surface ozone in the UK for a range of future scenarios

Exposure to surface ozone (O₃), which is influenced by emissions of precursor chemical species, meteorology and population distribution, is associated with excess mortality and respiratory morbidity. In this study, the EMEP-WRF atmospheric chemistry transport model was used to simulate surface O₃ concentrations at 5 km horizontal resolution over the British Isles for a baseline year of 2003, for three anthropogenic emissions scenarios for 2030, and for a + 5 °C increase in air temperature on the 2003 baseline. Deaths brought forward and hospitalisation burdens for 12 UK regions were calculated from population-weighted daily maximum 8-hour O₃. The magnitude of changes in annual mean surface O₃ over the UK for + 5 °C temperature (+ 1.0 to + 1.5 ppbv, depending on region) was comparable to those due to inter-annual meteorological variability (− 1.5 to + 1.5 ppbv) but considerably less than changes due to precursor emissions changes by 2030 (− 3.0 to + 3.5 ppbv, depending on scenario and region). Including population changes in 2030, both the ‘current legislation’ and ‘maximum feasible reduction’ scenarios yield greater O₃-attributable health burdens than the ‘high’ emission scenario: + 28%, + 22%, and + 16%, respectively, above 2003 baseline deaths brought forward (11,500) and respiratory hospital admissions (30,700), using O₃ exposure over the full year and no threshold for health effects. The health burdens are greatest under the ‘current legislation’ scenario because O₃ concentrations increase as a result of both increases in background O₃ concentration and decreases in UK NO_x emissions. For the + 5 °C scenario, and no threshold (and not including population increases), total UK health burden increases by 500 premature deaths (4%) relative to the 2003 baseline. If a 35 ppbv threshold for O₃ effects is assumed, health burdens are more sensitive to the current legislation and + 5 °C scenarios, although total health burdens are roughly an order of magnitude lower. In all scenarios, the assumption of a threshold increases the proportion of health burden in the south and east of the UK compared with the no threshold assumption. The study highlights that the total, and geographically-apportioned, O₃-attributable health burdens in the UK are highly sensitive to the future trends of hemispheric, regional and local emissions of O₃ precursors, and to the assumption of a threshold for O₃ effect.     

Dietary benzo(a)pyrene and fetal growth: Effect modification by vitamin C intake and glutathione S-transferase P1 polymorphism

BackgroundPrevious studies have reported maternal exposure to airborne polycyclic aromatic hydrocarbons (PAH), as well as DNA adducts reflecting total PAH exposure, to be associated with reduced fetal growth. The role of diet, the main source of PAH exposure among non-smokers, remains uncertain.ObjectiveTo assess associations between birth weight, length and small size for gestational age (SGA) with maternal intakes of the genotoxic PAH benzo(a)pyrene [B(a)P] during pregnancy, exploring potential effect modification by dietary intakes of vitamin C, vitamin E, alpha- and beta-carotene, as well as glutathione S-transferase P1 (GSTP1) polymorphisms, hypothesized to influence PAH metabolism.Methods657 women in the INMA (Environment and Childhood) Project from Sabadell (Barcelona) were recruited during the first trimester of pregnancy. Dietary B(a)P and nutrient intakes were estimated from food consumption data. Genotyping was conducted for the Ile105Val variant of GSTP1. Multivariable models were used to assess associations between size at birth and dietary B(a)P, evaluating potential interactions with candidate nutrients and GSTP1 variants.ResultsThere were significant interactions between elevated intakes of vitamin C (above the mean of 189.41 mg/day) and dietary B(a)P during the first trimester of pregnancy in models for birth weight and length (P < 0.05), but no interactions were found with other nutrients. B(a)P intakes were associated with significant reductions in birth weight and length (coefficient ± SE for a 1-SD increase in B(a)P: − 101.63 ± 34.62 g and − 0.38 ± 0.16 cm, respectively) among women with low, but not high, vitamin C intakes. Elevated dietary B(a)P was also associated with increased risk of SGA births among women with low dietary vitamin C. Among these women, associations were strongest in those carrying the GSTP1 Val allele, associated with lower contaminant detoxification activity.ConclusionResults suggest that dietary B(a)P exposure may impair fetal growth, particularly in genetically susceptible populations, and that increasing maternal intakes of vitamin C may help to reduce any adverse effects.     

Emerging and historical brominated flame retardants in peregrine falcon (Falco peregrinus) eggs from Canada and Spain

Comparisons of brominated flame retardants (BFRs) in the eggs of peregrine falcons (Falco peregrinus) recently collected (2003–2007), are made between Canada (N = 12) and Spain (N = 13). Overall, concentrations of sum (Σ) polybrominated diphenyl ethers (PBDEs; 16 di-deca-BDE congeners) exceeded Σhexabromocyclododecane (HBCD) and were an order of magnitude higher than 2,2′4,4′,5,5′-hexabromobiphenyl (BB-153) > hexachlorocyclopentenyl-dibromocyclooctane (HCBDCO) > 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) > decabromodiphenylethane (DBDPE) > octabromotrimethylphenyllindane (OBIND) > hexabromobenzene (HBB) > bis(2-ethyl-1hexyl)tetrabromophthalate (BEHTBP). This is the first report of detectable HBCDCO and BEHTBP concentrations in biota, and the highest in ovo concentration of ∑ HBCD (14,617 ng/g lw; Montreal, Canada) to date. There were significantly greater egg concentrations of BB-153, ΣHBCD, and ΣPBDE including BDE-153, -99, -100 and -183, in Canadian than Spanish peregrines with a terrestrial diet. HBB, BTBPE, and OBIND were detected in eggs from both countries, but only Canadian peregrine eggs had detectable levels of HCDBCO (25%) and DBDPE (N = 1). The in ovo PBDE congener profile was dominated by BDE-153 > BDE-99 > BDE-47 > BDE-183 > BDE-100 > BDE-209, with the isomeric HBCD pattern being α-HBCD > γ-HBCD (β-HBCD undetected). The Canadian peregrine eggs had lower enantiomeric HBCD values consistent with their higher fractions of (−) α-HBCD, suggesting selective enantiomeric enrichment or that the (+) α-isomer is more readily metabolized and so deposited in the egg through maternal transfer. Continental differences in egg burdens of peregrines are discussed relative to BFR usage patterns and exposure of peregrines on their breeding grounds.     

Substantial decline of polychlorinated biphenyls serum levels 10 years after public health interventions in a population living near a contaminated site in Northern Italy

IntroductionPolychlorinated biphenyls (PCBs) are persistent pollutants classified among endocrine disruptors and human carcinogens. In an urban area in Northern Italy (Brescia), a chemical factory producing PCBs from 1938 to 1984 caused soil and food pollution. Since the discovering of the environmental pollution in the area in 2001, various public health interventions have been implemented to avoid human contamination.MethodsTwo independent surveys were carried out in 2003 and 2013 using the same study design and methods. A random sample of the adult general population living in four areas of the town with different soil contamination level was enrolled in both surveys. Investigation included serum levels of 24 PCB congeners and of other common clinical-chemical parameters and questions about residential and occupational history as well as current and past diet and consumption of locally produced food. 537 subjects were tested in the 2003 and 488 in the 2013 survey.ResultsTotal PCB serum levels showed a strong correlation with age (Spearman r = 0.71 in 2003 and r = 0.80 in 2013), but not with gender. Consumers of food produced in the most polluted area had higher total PCB serum levels (median 15.6 and 4.7 ng/ml in 2003 and 2013, respectively) than non-consumers (4.1 and 2.3 ng/ml) and consumers of food produced in non-polluted areas (6.5 and 1.9 ng/ml), with increasing trend of PCB serum levels with cumulative local food intake. PCB serum levels from 2003 to 2013 survey declined by around half in all age groups, especially among the youngest people. The total PCB reduction was found to be due to a combination of a birth cohort effect (− 41% every 10 years) and survey period effect (− 18% in 2013 versus 2003), with medium chlorinated CB congeners showing the most relevant reduction (− 30%) between the two surveys. High chlorinated CBs were more strongly associated with birth cohort (− 46% every 10 years): in the 2013 survey they represented 58% of total PCBs in 60–79 years old while they were 37% among the under 40s with a median value 20 times higher in the oldest than in the youngest (3.1 versus 0.16 ng/ml).ConclusionsPCBs serum levels declined from the 2003 to 2013 survey though they are still high in the elderly mainly because of past intake of locally produced contaminated food. Present findings suggest that PCBs food chain contamination and human absorption have been interrupted successfully in the area since discovery of the pollution in 2001.     

Predictors of exposure to organophosphate pesticides in schoolchildren in the Province of Talca,Chile

BackgroundFew data exist in Latin America concerning the association between organophosphate (OP) urinary metabolites and the consumption of fruits and vegetables and other exposure risk variables in schoolchildren.MethodsWe collected samples of urine from 190 Chilean children aged 6–12 years, fruits and vegetables, water and soil from schools and homes, and sociodemographic data through a questionnaire. We measured urinary dialkylphosphate (DAP) OP metabolites and OP pesticide residues in food consumed by these 190 children during two seasons: December 2010 (summer) and May 2011 (fall). We analyzed the relationship between urinary DAP concentrations and pesticide residues in food, home pesticide use, and residential location.ResultsDiethylalkylphosphates (DEAP) and dimethylalkylphosphates (DMAP) were detected in urine in 76% and 27% of the samples, respectively. Factors associated with urinary DEAP included chlorpyrifos in consumed fruits (p < 0.0001), urinary creatinine (p < 0.0001), rural residence (p = 0.02) and age less than 9 years (p = 0.004). Factors associated with urinary DMAP included the presence of phosmet residues in fruits (p < 0.0001), close proximity to a farm (p = 0.002), home fenitrothion use (p = 0.009), and season (p < 0.0001).ConclusionsUrinary DAP levels in Chilean school children were high compared to previously reported studies. The presence of chlorpyrifos and phosmet residues in fruits was the major factor predicting urinary DAP metabolite concentrations in children.     

Assessment of human hair as an indicator of exposure to organophosphate flame retardants. Case study on a Norwegian mother–child cohort

A major challenge of non-invasive human biomonitoring using hair is to assess whether it can be used as an indicator of exposure to Flame Retardants, such as Organophosphate Flame Retardants (PFRs), since the contribution of atmospheric deposition (air and/or dust) cannot be neglected. Therefore, the aim of this study was to evaluate the suitability of using human hair more thoroughly by comparison of (i) levels of PFRs in human hair (from 48 mothers and 54 children), with levels measured in dust and air in their respective households; and (ii) levels of selected PFRs in hair with the levels of corresponding PFR metabolites in matching urine samples collected simultaneously. Most PFRs (tri-n-butyl phosphate (TNBP), 2-ethyl-hexyldiphenyl phosphate (EHDPHP), tri-phenyl phosphate (TPHP), tri-iso-butyl phosphate (TIBP), and tris(2-butoxyethyl) phosphate (TBOEP)) were detected in all human hair samples, tris(2-ethylhexyl) phosphate (TEHP) and tris(1,3-dichloro-iso-propyl) phosphate (TDCIPP) in 93%, tri-cresyl-phosphate (TCP) in 69% and tris(2-chloroethyl) phosphate (TCEP) in 21% of the samples. Levels of individual PFRs ranged between < 1 and 3744 ng/g hair and were lower than in indoor dust from the participants' homes. Several statistically significant associations between PFR levels in human hair and PFR levels in house dust and/or air were found, e.g. Spearman correlation (r_S = 0.561, p < 0.05) between TBOEP in children's hair and in indoor air. Also, associations were found between TDCIPP in hair and its metabolite bis(1,3-dichloro-iso-propyl) phosphate (BDCIPP) in urine; they were stronger for children (e.g. Pearson correlation r_P = 0.475; p = 0.001) than for mothers (r_P = 0.395, p = 0.01). Levels of diphenyl phosphate (DPHP) in mothers' and children's urine were slightly correlated (r_S = 0.409, p = 0.008), suggesting similar sources of exposure. To the best of our knowledge, this is the first study with such design and our findings might help to understand human exposure to and body burdens of PFRs.     

Perinatal exposure to dioxins and dioxin-like compounds and infant growth and body mass index at seven years: A pooled analysis of three European birth cohorts

BackgroundDioxins and dioxin-like compounds are endocrine disrupting chemicals (EDCs). Experimental studies suggest perinatal exposure to EDCs results in later obesity. However, the few epidemiological investigations on dioxins are inconclusive. We investigated perinatal exposure to dioxins and dioxin-like compounds, infant growth and body mass index (BMI) in childhood.MethodsWe pooled data from 3 European birth cohorts (Belgian, Norwegian, Slovak) with exposure assessment in cord blood or breast milk. Two cohorts had dioxin-like toxicity assessed using dioxin-responsive chemical-activated luciferase expression (DR-CALUX) bioassay and one cohort had measured concentrations of dioxins, furans and dioxin-like polychlorinated biphenols with CALUX relative potency values applied. Growth was cohort- and sex-specific change in weight-for-age z-score between birth and 24 months (N = 367). BMI was calculated at around 7 years (median 7.17, interquartile range [IQR] 7.00–7.37 years, N = 251), and overweight defined according to international standards for children equivalent to adult BMI > 25 kg/m² (Cole and Lobstein, 2012). We fitted multivariate models using generalized estimating equations, and tested effect modification by sex, breastfeeding and cohort. Results per 10 pg CALUX TEQ/g lipid increase in exposure.ResultsDioxin exposure was highest in the Belgian and lowest in the Norwegian cohort; median (IQR) of the pooled sample 13 (12.0) pg CALUX TEQ/g lipid. Perinatal exposure to dioxins and dioxin-like compounds appeared associated with increased growth between 0 and 24 months (adjusted estimate for change in z-score: β = 0.07, 95% CI: − 0.01, 0.14). At 7 years, dioxins exposure was associated with a statistically significant increase in BMI in girls (adjusted estimate for BMI units β = 0.49, 95% CI: 0.07, 0.91) but not in boys (β = − 0.03, 95% CI: − 0.55, 0.49) (p-interaction = 0.044). Furthermore, girls had a 54% (− 6%, 151%) increased risk of overweight at 7 years (p-interaction = 0.023).ConclusionPerinatal exposure to dioxin and dioxin-like compounds was associated with increased early infant growth, and increased BMI in school age girls. Studies in larger sample sizes are required to confirm these sex-specific effects.     

Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort

Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT) continues to be used for vector control in some malaria endemic areas. Previous findings from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study found increased prenatal levels of DDT and its breakdown product dichlorodiphenyl-dichloroethylene (DDE) to be associated with altered neurodevelopment in children at 1 and 2 years of age. In this study, we combined the measured maternal DDT/E concentrations during pregnancy obtained for the prospective birth cohort with predicted prenatal DDT and DDE levels estimated for a retrospective birth cohort. Using generalized estimating equation (GEE) and linear regression models, we evaluated the relationship of prenatal maternal DDT and DDE serum concentrations with children's cognition at ages 7 and 10.5 years as assessed using the Full Scale Intelligence Quotient (IQ) and 4 subtest scores (Working Memory, Perceptual Reasoning, Verbal Comprehension, and Processing Speed) of the Wechsler Intelligence Scale for Children (WISC). In GEE analyses incorporating both age 7 and 10.5 scores (n = 619), we found prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales (p-value > 0.05). In linear regression analyses assessing each time point separately, prenatal DDT levels were inversely associated with Processing Speed at age 7 years (n = 316), but prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales at age 10.5 years (n = 595). We found evidence for effect modification by sex. In girls, but not boys, prenatal DDE levels were inversely associated with Full Scale IQ and Processing Speed at age 7 years. We conclude that prenatal DDT levels may be associated with delayed Processing Speed in children at age 7 years and the relationship between prenatal DDE levels and children's cognitive development may be modified by sex, with girls being more adversely affected.     

Human exposure pathways to organophosphate triesters — A biomonitoring study of mother–child pairs

The worldwide ban of several formulations of brominated flame retardants has caused an increase in the production of organophosphorus flame retardants (PFRs) to meet the existing fire regulations for a wide range of household products. This biomonitoring study surveys the occurrence of the metabolites from PFRs and related plasticizers (dialkyl and diaryl phosphates; DAPs) in urine from a Norwegian mother–child cohort (48 mothers and 54 children). Concentrations of DAPs were higher in the children than in their mothers (Wilcoxon signed-rank test p = 0.001). Median urinary concentrations of diphenyl phosphate (DPHP) were 1.1 and 0.51 ng/mL in children and mothers, respectively, followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) with medians of 0.23 and 0.12 ng/mL, respectively. Detection frequencies for bis(2-butoxyethyl) phosphate (BBOEP) in urine from children and mothers were 32 and 1%, respectively (median < 0.18 ng/mL), and for di-n-butyl phosphate (DNBP) 15 and 8%, respectively (median < 0.12 ng/mL). The concentrations of DPHP and BDCIPP in urine from children were significantly correlated with those found for their parent compounds in air and dust from the households (Spearman's rank correlations 0.30 < R_s < 0.36; p < 0.05). For mothers, only the urinary concentration of BDCIPP was correlated to its precursor in dust from the households (R_s = 0.40; p < 0.01), which might indicate higher impact of the household environment on children than mothers. A diurnal variability study of the mothers' urinary concentrations of DPHP and BDCIPP showed lower concentrations at time periods when women were likely to be outside the household. In contrast, no relevant associations between organophosphate metabolites in urine and food consumption data obtained through a 24 hour recall were seen. This suggests that the residential environment is a more important exposure pathway to PFRs than the diet.