95th Percentile Concentrations Research Articles

Trend analyses of persistent organic pollutants in human milk from first-time mothers in Norway between 2002 and 2021

IntroductionPersistent organic pollutants (POPs) are stable compounds characterized by their resistance to degradation. From the 1960–70's organochlorine pesticides (OCPs), such as DDTs and polychlorinated biphenyls (PCBs) raised concerns regarding health and environmental impacts. This has led to the banning of POPs in the USA and Europe including Norway in 1980 and worldwide under the 2004 Stockholm Convention. The exposure of nursing infants to POPs has been a significant focus, prompting extensive research into the presence of these substances in human breast milk. In this study, we explored the temporal trends of POPs concentrations in breast milk sampled between 2002 and 2021 by comparing the concentration across the mother's year of birth. MethodTwo Norwegian cohorts of lactating women were utilized (the HUMIS study and the “Iodine in Early Life”-Study). Concentrations of 15 different POPs, including PCBs, OCPs, and brominated diphenyl ethers (BDEs) were measured in 513 breast milk samples that had been collected over two decades in a subset of first-time mothers. ResultsTime trend analysis indicated a steady decrease in concentration levels when adjusted for maternal age. The largest reduction was observed in β-HCH, age-adjusted (−17.1%, 95% CI -18.7, −15.4), followed by ∑6BDE (−9.1%, 95% CI -10.5, −7.7), ∑6PCBs (−7.1%, 95% CI -7.7, −6.5), and ∑2DDTs (−7.0%, 95% CI -8.0, −6.0). In contrast, an increasing trend was noted in the median concentrations of β-HCH, ∑2DDTs, and ∑6BDE in the mothers born in 1990–1994 to 1995–2002. ConclusionOur study demonstrates a decline of most POPs in breast milk, likely attributed to international regulatory efforts like the Stockholm Convention. Notably, an increase in the 95th percentile concentrations of β-HCH, ∑2DDTs, and ∑6BDEs was noted in mothers born in 1990–1994 compared to those born in 1995–2002 suggests demographic shifts that may influence exposure levels. Further research is needed to explore and understand the underlying factors for the rise in median concentrations of ∑6BDEs.

Airborne concentrations of bacteria and mold in Korean public-use facilities: measurement, systematic review, meta-analysis, and probabilistic human inhalation risk assessment.

Bioaerosols adversely affect human health posing risk to users of public facilities in Korea. Between October 2021 and May 2022, airborne bacteria and mold were measured in 1,243 public-use facilities across 23 categories. A systematic review and meta-analysis were performed on these and other studies from June 2004 to May 2021, and the non-carcinogenic risks to humans were assessed using Monte Carlo simulations. For bacteria, the maximum 95th percentile concentration was 584.4cfu/m3 and 1384.8cfu/m3 for mold. The heterogeneity statistic I2 was over 50% in all facilities, and for subway station bacteria, there was a significant difference according to the measurement method. The 95th percentile of hazard by population group was 8.83 × 10-2 to 3.42 × 10-1 for bacteria, and 1.31 × 10-1 to 3.55 × 10-1 for mold. The probability of a hazard quotient exceeding 1 for some population groups was derived from exposure to bacteria and mold in the air resulting from the use of all public facilities. The most powerful explanatory factor for risk was exposure time to the facility, both within (up to 0.922 for bacteria and up to 0.960 for mold) and between populations (up to 0.543 for bacteria and 0.483 for mold). This study identified populations at risk of bioaerosol exposure in Korean public-use facilities and estimated the influencing factors, highlighting the need for comprehensive improvement in bioaerosol control in public-use facilities.

Fluorinated liquid-crystal monomers in infant formulas and implication for health risk

Fluorinated liquid-crystal monomers (FLCMs), a new class of potential persistent, bioaccumulative and toxic (PBT) emerging pollutants, are extensively utilized in the display panel of various electronic devices. These compounds have been found in various environmental matrixes and dietary. Our previous studies have documented their ubiquitous occurrence in high fat foodstuffs. Infants, a vulnerable group, are more susceptible to the impacts of these pollutants compared to adults. Herein, we provided an assessment of the health risks posed by FLCMs to infants, focusing on their exposure through infant formula. The presence of FLCMs was detected in all infant formulas, with median concentration of 16.5 ng/g dry weight (dw) and the 95th percentile concentration of 65.7 ng/g dw. The most prevalent pollutant in these formulas was 2-fluoro-4-[4′-propyl-1,1′-bi(cyclohexyl)-4-yl] phenyl trifluoromethyl ether (FPrBP), with median and a 95th percentile concentration of 12.2 ng/g dw and 23.8 ng/g dw, accounting for 55.2% to the total FLCMs. Infants aged 0–6 months had the highest estimated daily intakes (EDIs) of FLCMs, with the EDImedian of 267 ng/kg bw/day. FPrBP and 4-[trans-4-(trans-4-Propylcyclohexyl) cyclohexyl]-1-trifluoromethoxybenzene (PCTB) together made up 83.3% of the total EDIs in median exposure scenario of 0–6 months infant. The highest EDI value was 1.30 × 103 ng/kg bw/day, 77.1% of which was attributed to a combination of FPrBP, 4″-ethyl-2′-fluoro-4-propyl-1,1':4′,1″-terphenyl (EFPT), 2-[4'-[difluoro(3,4,5-trifluoro-2-methyl-phenoxy)methyl]-3′,5′-difluoro-[1,1′-biphenyl]-4-yl]-5-ethyl-tetrahydro-pyran (DTMPMDP), 4-[Difluoro-(3,4,5-trifluoro-2-methyl-phenoxy)-methyl]-3,5-difluoro-4′-propyl-1,1-biphenyl (DTMPMDB), 2,3-difluoro-1-methyl-4-[(trans, trans)-4′-pentyl[1,1′-bicyclohexyl]-4-yl]benzene (DMPBB) and PCTB. It's worth noting that FLCMs have higher exposure risk. Based on the threshold of toxicological concern (TTC) method, the EDImedian of FPrBP (183 ng/kg bw/day) and FPCB (3.27 ng/kg bw/day) were beyond their TTC values (2.5 ng/kg bw/day) in 0–6 months infant, implying their prospective health risk.

Air pollutants, seasonal influenza, and acute otitis media in children: a population-based analysis using 22-year hospitalization data

BackgroundAcute otitis media (AOM) is a prevalent childhood acute illness, with 13.6 million pediatric office visits annually, often stemming from upper respiratory tract infections (URI) and affected by environmental factors like air pollution and cold seasons.MethodsHerein, we made use of territory-wide hospitalization data to investigate the relationships between meteorological factors, air pollutants, influenza infection, and AOM for children observed from 1998 to 2019 in Hong Kong. Quasi-Poisson generalized additive model, combined with a distributed-lag non-linear model, was employed to examine the relationship between weekly AOM admissions in children and weekly influenza-like illness-positive (ILI +) rates, as well as air pollutants (i.e., oxidant gases, sulfur dioxide, and fine particulate matter), while accounting for meteorological variations.ResultsThere were 21,224 hospital admissions due to AOM for children aged ≤ 15 years throughout a 22-year period. The cumulative adjusted relative risks (ARR) of AOM were 1.15 (95% CI, 1.04–1.28) and 1.07 (95% CI, 0.97–1.18) at the 95th percentile concentration of oxidant gases (65.9 ppm) and fine particulate matter (62.2 μg/m3) respectively, with reference set to their medians of concentration. The ARRs exhibited a monotone increasing trend for all-type and type-specific ILI + rates. Setting the reference to zero, the cumulative ARRs of AOM rose to 1.42 (95% CI, 1.29–1.56) at the 95th percentile of ILI + Total rate, and to 1.07 (95% CI, 1.01–1.14), 1.19 (95% CI, 1.11–1.27), and 1.22 (95% CI, 1.13–1.32) for ILI + A/H1N1, A/H3N2, and B, respectively.ConclusionsOur findings suggested that policy on air pollution control and influenza vaccination for children need to be implemented, which might have significant implications for preventing AOM in children.

Analysis of chemical exposures in racial populations in Canada: An investigation based on the Canadian health measures survey

Despite demonstrated disparities in environmental chemical exposures by racial identity, no Canadian study has systematically assessed the feasibility of using a nationally representative dataset to examine differences in chemical concentrations by race. We assessed the feasibility and constraints of analysing chemical exposures in racial populations, including visible minorities and populations of Indigenous identity, using biomonitoring data collected through the Canadian Health Measures Survey (CHMS). Our primary objectives were to assess the ability to 1) generate geometric means and percentiles of chemical concentrations for racial populations by age or sex, 2) statistically compare concentrations among racial populations, and 3) calculate time trends of concentrations by race. We conducted these analyses for several priority chemicals: lead, cadmium, benzene, bisphenol A (BPA), and di(2-ethylhexyl) phthalate (DEHP). Survey participants self-identified as one of the following: White, Black, East and Southeast Asian, South Asian, Middle Eastern, Latin American, First Nations, Metis, and Inuit. Analyses were conducted for individual and combined cycles of the CHMS. Using data from the latest CHMS cycle in which each chemical was measured, we observed that sample sizes were sufficient to report geometric mean concentrations for all races except Inuit. Due to privacy considerations associated with small sample sizes, the 5th and 95th percentile concentrations could not be consistently reported for all racial populations in this analysis. While we were able to statistically compare concentrations among racial populations, the analysis was constrained by the limited number of statistical degrees of freedom available in a single CHMS cycle. Both of these constraints were alleviated by combining multiple cycles of data. The analysis of time trends was less subject to privacy and statistical limitations; we were able to calculate time trends of chemical concentrations for all racial populations. Our findings provide an important baseline for follow-up investigations of descriptive and etiological analyses of environmental chemical exposures and race in the CHMS.

Carcinogenic metal(loid)s in house dust compared to soil: Concentrations and gastric bioaccessibility

As a sink and a source of chemicals, house dust represents a relevant medium to assess indoor exposure to metal(loid)s via incidental ingestion or inhalation. However, nationally representative indoor data are scarce. Results from the Canadian House Dust Study (CHDS, 2007–2010; n = 1025) provide nationally representative mean, median and 95th percentile concentrations for 38 elements in typical urban house dust, along with their gastric bioaccessibility. Total concentrations (median/95th percentile) of carcinogenic metal(loid)s in Canadian house dust (μg g−1) are as follows: As (9.0/40), Be (0.4/0.9), Cd (3.5/17), Co (5.6/19), Cr (99/214), Ni (62/322) and Pb (100/760). Total As and Pb concentrations in house dust exceed residential soil guidelines for the protection of human health in about one-third of Canadian homes. Percent bioaccessibilities (median) are: Cd (65%) > Pb (63%) > Be ∼ Ni (36%) > Co (35%) > As (20%) > Cr (15%). Lead, Cd and Co concentrations are significantly greater in older houses (< 1976). Data from two pilot studies (n = 66 + 51) further demonstrate the distinct geochemistry of house dust compared to soils, notably enrichment of carcinogenic metal(loid)s and their increased bioaccessibility. These results provide essential baseline values to refine risk assessment and inform on health risk at contaminated sites.

Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats

This study explored the effect of a toxic metal(oid) mixture (cadmium, lead, arsenic, mercury, chromium, and nickel) on thyroid function in Wistar rats exposed for 28 or 90 days. Dose levels were determined based on prior human-biomonitoring investigation. The experiment included control (male/female rats, 28 and 90 days) and treated groups, reflecting the lower confidence limit of the Benchmark Dose (BMDL) for hormone levels (M1/F1, 28 and 90 days), median concentrations (M2/F2, 28 and 90 days), 95th percentile concentrations (M3/F3, 28 and 90 days) measured in a human study, and reference values for individual metals extracted from the literature (M4/F4, 28 days only). Blood and thyroid gland samples were collected at the experimental termination. Serum TSH, fT3, fT4, T3, and T4 levels were measured, and SPINA-GT and SPINA-GD parameters were calculated. In silico analysis, employing the Comparative Toxicogenomic Database and ToppGene Suite portal, aimed to reveal molecular mechanisms underlying the observed effects. Results showed greater sensitivity in the female rats, with significant effects observed at lower doses. Subacute exposure increased TSH, fT3, and T3 levels in females, while subchronic exposure in males decreased TSH and fT3 levels and increased fT4. Subacute exposure induced changes even at allegedly safe doses, emphasizing potential health risks. Histological abnormalities were observed in all the treated groups. In silico findings suggested that toxic metal exposure contributes to thyroid disorders via oxidative stress, disruption of micronutrients, interference with hormone synthesis, and gene expression dysregulation. These results indicate that seemingly safe doses in single-substance research can adversely affect thyroid structure and function when administered as a mixture. These findings highlight the complex impact of toxic metal exposure on thyroid health, emphasizing that adhering to accepted safety limits for single-substance research fails to account for adverse effects on thyroid structure and function upon exposures to metal mixtures.

Occurrence and exposure evaluation of 2- and 3-monochloropropanediol (MCPD) esters and glycidyl esters in refined vegetable oils marketed in Tianjin of China

2-and 3-monochloropropanediol esters (2-/3-MCPDE) and glycidyl esters (GE) with high toxicity have drawn global concerns due to their widespread occurrence in refined vegetable oils and oil-based foods. In this study, we investigated the contamination level and human health risks of 2-MCPDE, 3-MCPDE and GE in refined vegetable oils marketed in Tianjin of China. Results showed that the concentrations of 2-MCPDE, 3-MCPDE and GE in the 137 vegetable oil samples were in the range of not detected (ND) −6.95 mg/kg, ND-8.39 mg/kg and ND-5.46 mg/kg, respectively. The mean, 50th percentile and 95th percentile concentrations of 3-MCPDE were higher than the corresponding concentration of 2-MCPDE and GE in different types of oils samples. Among the samples analyzed, 29 samples (21.2%) exceeded the maximum levels (2.5 mg/kg) for 3-MCPDE, while 25 samples (18.2%) exceeded the maximum levels (1.0 mg/kg) for GE. The estimated intakes of 3-MCPDE of high consumers of children (7–10 years), adolescents (11–13 years) exceeded the tolerated daily intake (TDI) value of 2 µg/kg bw per day established by EFSA, suggesting a potential concern. The Margin of Exposure (MoE) values for glycidol exposure via vegetable oils consumption in all age groups indicated there is a human health concern.

Assessment of transfer factor of potential toxic elements (PTEs) in aloe vera plant

ABSTRACT Aloe Vera plants are widely used for cosmetic, health and Medicinal purposes. Various studies have highlighted the nutritional and health benefits of Aloe Vera plants, but few studies have investigated their bioconcentration of pollutants. The main aim of our study was to estimate transfer factor (TF) of potential toxic elements (PTEs) in aloe vera gel. We estimated of PTEs including arsenic (As), cadmium (Cd), iron (Fe), nickel (Ni), lead (Pb), and zinc (Zn), in 5 groups of aloe vera plants. After 6 weeks we sampled the aloe vera gel and soil and detected the concentration of PTEs using inductively coupled plasma optical emission spectrometry (ICP-OES). We then estimated the concentration of PTEs in aloe vera gel in Iran using the results of a meta-analysis of PTEs in agricultural soil in Iran and a Monte Carlo Simulation (MCS) model. The mean (± SD) TF for Fe, Pb, As, Cd, Zn, and Ni were equal to 0.558 ± 2.487%, 0.555 ± 1.225%, 0.163 ± 0.372%, 0.122 ± 1.123%, 0.069 ± 0.415% and 0.032 ± 0.748%, respectively. The rank order of PTEs, based on their TF, was Fe > Pb > As > Cd > Zn > Ni. Moreover, the rank order of PTEs, based on the 95th percentile of concentrations in Aloe vera gel in Iran, was Pb (0.7828 mg/kg) > As (0.2800 mg/kg) > Zn (0.1601 mg/kg) > Cd (0.0444 mg/kg). TF of PTEs in Aloe vera gel were less than 1, which shows natural levels of metals in plant tissues. On the other hand, the 95th percentile concentration of PTEs in aloe vera gel was lower than the standard limits. Hence, aloe vera gel cannot threaten the health of consumers due to PTEs.

Combustion of high-calorific industrial waste in conventional brick kilns: An emerging source of PFAS emissions to agricultural soils

The brick kilns in the South Asian region are widely documented to partially combust high-calorific waste components of synthetic-industrial origin, which contain hazardous constituents, including per- and polyfluoroalkyl substances (PFAS). Correspondingly, these establishments are necessarily built on agricultural land to easily acquire clay by excavating soil horizons, thus making cultivation soils vulnerable to PFAS contaminations. In this pioneering study, the occurrence, distribution profile, traceability and human health risk exposure to forty-four legacy and novel PFAS homologues, including two ultrashort-chain (C2-C3) PFAS, were investigated in agricultural soils around thirty-two conventional brick kilns across three districts of Pakistan. ⅀44PFAS concentrations ranged from 14.3 to 465 ng/g (median: 28.2 ng/g), which were 2 to 70 folds higher than those in background soils, and slightly higher than those reported in agricultural soils in the global literature. The highest occurrence was observed for PFAS alternatives, i.e., 6:2 fluorotelomer sulfonate (6:2 FTSA) (40 %) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) (4.5 %). A significant positive correlation (p < 0.01) was observed among the concentrations of short-chain perfluoroalkyl acids (C4-C7) and novel PFOS substitutes, implying their origin from common sources. Furthermore, ultrashort-chain and short-chain perfluorocarboxylic acids (PFCA) (89 %) and perfluorosulfonic acids (PFSA) (63 %) dominated over long-chain's PFCA (11 %) and PFSA (37 %), respectively. The estimated daily intake to children exposed in surrounding inhabited communities, at 95th percentile concentrations was found to be approaching the European tolerable daily intake limit of 0.63 ng/kg bw/day. Therefore, the brick manufacturing industry is identified as a novel source of PFAS in the adjacent environment and for residents. This suggests the need for further investigations to elucidate the origin of emerging contaminants in the waste streams of the region to safeguard ecological integrity.

Dimethylsiloxanes in dust from nine indoor microenvironments of Henan Province: Occurrence and human exposure assessment

Dimethylsiloxanes (MSs) are widely used in daily life and industry, with indoors being the main release site. Detecting the levels of MSs in indoor dust is essential for assessing the risks of human exposure. In this study, the content of MSs (D3–D8 and L3–L16) was quantified in indoor dust samples from nine microenvironments of Henan Province. The detection frequency of the targets ranged from 5.00 % to 100 %. The sum concentration of dimethylsiloxanes (TSi) was in a range of 463–3.32 × 104 ng·g−1 (median: 1.92 × 103 ng·g−1). The sum concentration of linear dimethylsiloxanes (TLSi) from all microenvironments was higher than the sum concentration of cyclic dimethylsiloxanes (TCSi), which was consistent with previously reported results. D7 and D8 were the main cyclic dimethylsiloxane, which had similar sources based on Spearman correlation analysis (p < 0.001). Moreover, D8 was detected with high levels in indoor dust for the first time, which warrants further exploration. L8–L16 were the main linear dimethylsiloxanes, which may have been due to their widespread use in electronic equipment and office equipment. The Spearman analysis found that total organic carbon (TOC) in indoor dust had weak effect on MSs. Additionally, relatively high MS levels were recorded in high people-flow working microenvironments. Accordingly, the exposure doses of MSs via indoor dust intake were estimated for different age groups using the model of worst-case exposure and median concentration. Toddlers had the highest EDIs (95th percentile concentration, 90.7 ng·kg−1-bw·d−1) to MSs.

Cleaner air for vulnerable people – Finding better locations for essential building premises

Long-term exposure to ambient air pollution even at relatively low concentrations is associated with adverse health effects especially for children, the elderly and people with pre-existing chronic disease. Due to a variety of urban planning decisions, essential building premises attended by these vulnerable groups may be sited in locations exposed to higher levels of air pollution. Using high spatial resolution air pollution concentrations estimated by satellite-based Land Use Regression (LUR) models in Australia, we mapped and approximated the annual average concentrations of particulate matter (PM2.5) and nitrogen dioxide (NO2) at schools, child care centres, aged care facilities and hospitals across Sydney. We found that 137 (3.1 %) and 287 (6.4 %) of the total number of essential buildings assessed were exposed to annual average PM2.5 and NO2 concentrations, respectively, where: the air pollutant concentrations were greater than the median concentration of other locations in the surrounding Local Government Area (LGA), and; air pollutant levels were greater than the 90th percentile concentrations for Sydney, and; air pollution at the essential building location was at least 1 µg/m3 for PM2.5 or 2 ppb for NO2 greater than the 25th percentile concentration of other locations in the LGA. Based on these criteria, we found that many essential building premises in Sydney were in high air pollution locations and there were other meaningfully lower air pollution locations within the surrounding area. Air quality is becoming an increasingly important issue for local jurisdictions to consider as more essential amenities are required to serve denser populations in busier places exposed to more air pollution. Our study showed that high resolution maps can be used as a health-based planning tool to encourage the siting of buildings at locations better protective of health.

Effects of the real-life metal(oid)s mixture on female reproductive function: Less is different

The current study aimed to examine the effect of toxic metal(oid) mixtures (lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), and nickel (Ni)) on female reproductive function in Wistar rats after the 28- and 90-day exposure to dose levels calculated on the basis of the previously conducted human study. Experimental groups included: 2 controls (28- and 90-day), treated groups - doses based on: median– F2 (28) and F2(90) and 95th percentile concentrations in the general human population – F3(28) and F3(90); calculated lower Benchmark dose confidence limit (BMDL) for effects on hormone levels – F1(28) and F1(90) and a group given the doses calculated on the basis of the reference values from the literature (F4(28)). Blood and ovarian samples were collected for sex hormones and ovary redox status analysis. After 28-day exposure, changes were present both in prooxidants and antioxidants. However, after the 90-day exposure redox status imbalance was majorly caused by the disturbance of antioxidants. Changes in some parameters were observed even after exposure to the lowest doses. After 28-day exposure, the strongest dose-response relationship was found between hormones: LH and FSH and toxic metal(oid)s and, after 90-day exposure, between investigated redox status parameters: sulfhydryl groups, ischemia-modified albumin and nuclear factor erythroid 2–related factor 2 (Nrf2) and toxic metal(oid)s. Low obtained BMDLs and narrow Benchmark intervals for toxic metal(oid)s and some of the parameters might confirm the “no-threshold” paradigm. This study indicates possible detrimental effects of prolonged exposure to real-life mixtures of toxic metal(oid) on female reproductive function.

Human dietary exposure to bisphenol-diglycidyl ethers in China: Comprehensive assessment through a total diet study

Despite the widespread use of bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE) in various consumer products as protective plasticizer, studies on human dietary exposure to these compounds are scare. In this study, nine bisphenol diglycidyl ethers (BDGEs) including BADGE, BFDGE, and seven of their derivatives were determined in the Chinese adult population based on composite dietary samples collected from the sixth (2016–2019) China total diet study (TDS). Contamination level of nine BDGEs was determined in 288 composite dietary samples from 24 provinces in China. BADGE·2H2O and BADGE are the most frequently detected and BADGE·2H2O presented the highest mean concentration (2.402 μg/kg). The most contaminated food composite is meats, with a mean ∑9BDGEs of 8.203 μg/kg, followed by aquatic products (4.255 μg/kg), eggs (4.045 μg/kg), and dairy products (3.256 μg/kg). The estimated daily intake (EDI) of ∑9BDGEs based on the mean and 95th percentile concentrations are 121.27 ng/kg bw/day and 249.71 ng/kg bw/day. Meats, eggs, and aquatic products are the main source of dietary exposure. Notably, beverages and water, alcohols were the main contributors of dietary exposure to BADGE and BADGE·2H2O, followed by animal-derived foods. Dietary exposure assessment demonstrated that human dietary BDGEs do not pose risks to general population based on the mean and 95th percentile hazard index with < 1. This is the first comprehensive national dietary exposure assessment of BDGEs in Chinese general population.

Fatal concentrations of antidepressants and antipsychotics in post-mortem blood

The objective was to compare the summary statistics for fatal antidepressant and antipsychotic drug concentrations mined by different approaches from post-mortem (PM) toxicological data. Reference concentrations of drugs play a major part in the interpretation of PM toxicology results. However, PM drug concentrations are not necessarily the same as those at the time of death, and consequently standard tables of clinical plasma concentration data are of limited value. Compilations of PM concentrations collected from literature sources are often heterogeneous in terms of the sampling site, the analytical methods used, and the number of cases involved. However, there are also published summary statistics for drug concentrations in PM femoral venous blood, based on extensive databases from centralized laboratories with well-established and high-quality working practices. The present study establishes concentration distributions for a number of antidepressant and antipsychotic drugs, specified as a principal finding in fatal poisoning (principal finding approach). These levels are then compared with those obtained using two previous approaches: according to the all-causes-of-death (Ketola RA, Drug Test Anal, 2019, 11, 1326–1337) or according to the grouped causes of death, aka “the Druid approach”, where the reference information is subdivided into poisonings by one specific substance only, multi-substance poisonings and non-poisoning controls (Reis M, J Anal Toxicol, 2007, 31, 254-264; Söderberg C, Forensic Sci Int, 2016, 266, 91-101). Summary statistics for fatal antidepressant and antipsychotic drug concentrations in PM femoral venous blood were generated according to the principal drug finding. In most cases, also other drugs were implicated in the cause of death. The data were mined between 2000–2020 from the national PM toxicology database, maintained by the Finnish Institute for Health and Welfare, in which all results of the toxicological analyses in medico-legal investigations and information from the respective death certificates are collected. From this material, those antidepressant and antipsychotic drugs that had been quantitatively analysed at least 10 times were selected. Concentration percentiles (10th, 50th, 90th, 95th, 97.5th) were calculated for 16 different antidepressant ( N = 1999) and for 7 different antipsychotic drugs ( N = 1134), defined as principal findings of fatal poisoning by forensic pathologists. For instance, for the antidepressant amitriptyline the respective concentrations were 0.66, 2.0, 8.3, 13 and 25 mg/L, and for the antipsychotic levomepromazine (methotrimeprazine) 0.40, 1.5, 5.3, 10 and 16 mg/L. A comparison with other data mining approaches will be presented in visual form. A clear correspondence was found between, for example, the 90th percentile concentration level of the present principal finding approach and the 97.5th percentile concentration level of the all-causes-of-death approach. Similarly, a correspondence was found between, for example, the median concentration level of the present principal finding approach and the median concentration level of the multi-substance poisoning group in the Druid approach. The novel data presented in this study followed by a systematic comparison with data from previous studies helps rationalize the use of reference concentrations from various sources in the interpretation of potential poisoning deaths. Further data mining for additional drugs will be markedly easier in the principal finding approach than in the Druid approach, provided that the principal findings are specified in advance in the database as is in our case. Despite the proven usefulness of reference concentrations, interpretation must always be made on a case-by-case basis, taking into account e.g. background information, autopsy findings, and substance interactions. A forensic toxicologist must have the evidence-based PM concentration information at his or her disposal when assisting a forensic pathologist in determining the cause of death or being called to testify in court.

Occurrence and removal of drugs and endocrine disruptors in water supply systems in the metropolitan region of Belo Horizonte (Minas Gerais State, Brazil)

This study evaluates both the occurrence and removal of 24 compounds, including drugs and endocrine disruptors, in 8 water treatment plants (WTP) located in the metropolitan region of Belo Horizonte (Minas Gerais State, Brazil). The compounds 4-nonylphenol, 4-octylphenol, 17α-ethinylestradiol, 17β-estradiol, acyclovir, bisphenol A, bezafibrate, caffeine, dexamethasone, diclofenac sodium, diltiazem, estrone, estriol, gemfibrozil, ibuprofen, linezolid, loratadine, losartan, metformin, naproxen, paracetamol, promethazine, propranolol and sulfamethoxazole were monitored at 3 sampling points (raw water, filtered water, treated water) over 10 or 12 collection campaigns for each WTP. The results showed that bisphenol A occurred at higher concentrations during the dry period with a maximum concentration of 3257.1ng L-1, while the compounds 4-nonylphenol and losartan exhibited higher concentrations in the rainy period with maximum concentrations of 8577.2ng L-1 and 705.8ng L-1, respectively. Regarding the removal of compounds in the monitored WTPs, the clarification step demonstrated better removals for 4-nonylphenol, bisphenol-A, paracetamol, and sulfamethoxazole, whereas the disinfection step mainly removed the compounds 4-octylphenol and estrone. Margin of exposure (ME) assessment results indicated that only dexamethasone, ethinyl estradiol, diclofenac, estradiol, and estrone were classified as imminent risk or alert considering the 95th percentile concentration found in the samples of treated water.

Urinary tetracycline antibiotics exposure during pregnancy and maternal thyroid hormone parameters: A repeated measures study

BackgroundStudies on potential maternal thyrotoxicity related to tetracycline antibiotics exposure during pregnancy are lacking. Based on a large prospective cohort study, this study aimed to examine the associations between tetracycline antibiotics exposure in maternal urine and maternal thyroid hormone parameters. MethodsBased on the Ma'anshan Birth Cohort study, urine and serum samples of 2969 pregnant women were collected in the first, second and third trimesters. Tetracycline antibiotics, including oxytetracycline, chlorotetracycline, tetracycline and doxycycline in urine samples, as well as free thyroxine (FT4), thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) levels in serum samples, were measured. Linear mixed models and multivariate linear regression models were employed to examine associations between tetracycline antibiotics exposure during pregnancy and maternal thyroid hormone parameters. ResultsThe detection rates of four individual tetracycline antibiotics and all antibiotics (sum of four individual tetracycline antibiotics) in the three trimesters were 5.0%–52.3%, and the 95th percentile concentration ranged from 0.11 to 4.84 ng/mL. After adjusting for potential confounding factors, the repeated measures analyses indicated that pregnant women exposed to doxycycline and all antibiotics during the entire pregnancy were negatively associated with serum FT4 and TT4 levels but positively associated with serum TSH and TT3 levels. Trimester-stratified analyses found that doxycycline and all antibiotics exposure during the first trimester were negatively associated with serum FT4 and TT4 levels, while doxycycline was positively associated with TSH levels. In the third trimester, a significant association was only found between all antibiotics and TSH levels. ConclusionsOur results suggest that exposure of pregnant women to tetracycline antibiotics is associated with maternal thyroid hormone parameters, and the first trimester might be the most critical window. More studies are needed to substantiate our findings and determine the underlying biological mechanisms.

The first detection of quaternary ammonium compounds in breast milk: Implications for early-life exposure.

BackgroundQuaternary ammonium compounds (QACs), commonly used in cleaning, disinfecting, and personal care products, have recently gained worldwide attention due to the massive use of disinfectants during the COVID-19 pandemic. However, despite extensive use of these chemicals, no studies have focused on the analysis of QACs in human milk, a major route of exposure for infants. ObjectiveOur objectives were to identify and measure QACs in breast milk and evaluate early-life exposure to this group of compounds for nursing infants.MethodsEighteen QACs, including 6 benzylalkyldimethyl ammonium compounds (BACs, with alkyl chain lengths of C8-C18), 6 dialkyldimethyl ammonium compounds (DDACs, C8-C18), and 6 alkyltrimethyl ammonium compounds (ATMACs, C8-C18), were measured in breast milk samples collected from U.S. mothers. Daily lactational intake was estimated based on the determined concentrations for 0–12 month old nursing infants.ResultsThirteen of the 18 QACs were detected in breast milk and 7 of them were found in more than half of the samples. The total QAC concentrations (ΣQAC) ranged from 0.33 to 7.4 ng/mL (median 1.5 ng/mL). The most abundant QAC was C14-BAC with a median concentration of 0.45 ng/mL. The highest median ΣQAC estimated daily intake (EDI) was determined for <1-month old infants based on the average (using the median concentration) and high (using the 95th percentile concentration) exposure scenarios (230 and 750 ng/kg body weight/day, respectively).SignificanceOur findings provide the first evidence of the detection of several QACs in breast milk and identify breastfeeding as an exposure pathway to QACs for nursing infants.Impact statementOur findings provide the first evidence of QAC occurrence in breast milk and identify breastfeeding as one of the exposure pathways to QACs for nursing infants.

Sociodemographic inequalities in uranium and other metals in community water systems across the USA, 2006–11: a cross-sectional study

SummaryBackgroundThe US Environmental Protection Agency (EPA) currently sets maximum contaminant levels (MCLs) for ten metals or metalloids in public drinking water systems. Our objective was to estimate metal concentrations in community water systems (CWSs) across the USA, to establish if sociodemographic or regional inequalities in the metal concentrations exist, and to identify patterns of concentrations for these metals as a mixture.MethodsWe evaluated routine compliance monitoring records for antimony, arsenic, barium, beryllium, cadmium, chromium, mercury, selenium, thallium, and uranium, collected from 2006–11 (2000–11 for uranium; timeframe based on compliance monitoring requirements) by the US EPA in support of their second and third Six-Year Reviews for CWSs. Arsenic, barium, chromium, selenium, and uranium (detectable in >10% records) were included in the main analyses (subgroup and metal mixture analyses; arsenic data reported previously). We compared the mean, 75th percentile, and 95th percentile contaminant concentrations and the percentage of CWSs with concentrations exceeding the MCL across subgroups (region, sociodemographic county-cluster, size of population served, source water type, and CWSs exclusively serving correctional facilities). We evaluated patterns in CWS metal concentration estimate profiles via hierarchical cluster analysis. We created an online interactive map and dashboard of estimated CWS metal concentrations for use in future analyses.FindingsAverage metal concentrations were available for a total of 37 915 CWSs across the USA. The total number of monitoring records available was approximately 297 000 for arsenic, 165 000 for barium, 167 000 for chromium, 165 000 for selenium, and 128 000 for uranium. The percentage of analysed CWSs with average concentrations exceeding the MCL was 2·6% for arsenic (MCL=10 μg/L; nationwide mean 1·77 μg/L; n=36 798 CWSs), 2·1% for uranium (MCL=30 μg/L; nationwide mean 4·37 μg/L; n=14 503 CWSs), and less than 0·1% for the other metals. The number of records with detections was highest for uranium (63·1%). 75th and 95th percentile concentrations for uranium, chromium, barium, and selenium were highest for CWSs serving Semi-Urban, Hispanic communities, CWSs reliant on groundwater, and CWSs in the Central Midwest. Hierarchical cluster analysis revealed two distinct clusters: an arsenic–uranium–selenium cluster and a barium–chromium cluster.InterpretationsUranium is an under-recognised contaminant in CWSs. Metal concentrations (including uranium) are elevated in CWSs serving Semi-Urban, Hispanic communities independent of location or region, highlighting environmental justice concerns.FundingUS National Institutes of Health Office of the Director, US National Institutes for Environmental Health Sciences, and US National Institute of Dental and Craniofacial Research.

Exposure of preschool-aged children to highly-concerned bisphenol analogues in Nanjing, East China

Bisphenol analogues (BPs) have already attracted wide concern owing to the environmental and health risks they pose. The exposure pathways and health risk of preschool-aged children to BPs, however, are still poorly understood. In this study, we choose population survey with 184 preschool-age children from a suburb of Nanjing, eastern China, further reveal the internal and external exposures concentrations, distribution profiles, potential sources and eventually assess health risk of preschool-age children to eight kinds of BPs. The results verify that the 95th percentile (P95) concentrations of Ʃ8BPs ranged from 0.27 to 41.6 ng/mL, with a median concentration of 7.83 ng/mL in the urine samples. BPA, and BPF were the predominant BPs in urine, accounting for 67.3%, and 18.0% of Ʃ8BPs. The urine-based estimated daily intake (EDI) of Ʃ8BPs was 187 ng/kg body weight/day. Similarly, BPA, and BPF were the main BPs in the environmental exposure sources, accounting for 80.8%, and 11.7% of the total BPs. Moreover, the total external exposure dose of Ʃ8BPs via the environmental sources was 68.1 ng/kg body weight/day, including BPA (56 ng/kg body weight/day), BPF (7.68 ng/kg body weight/day) and BPB (2.62 ng/kg body weight/day). The oral intake of drinking water and food (vegetables and rice) was the main exposure pathways of BPs in preschool-age children. Furthermore, the hazard quotient (HQ) of BPs have been evaluated and the results show no occurrence of high risk. Additionally, the urine-based EDI was significantly higher than the total external exposure dose, suggesting the existence of other pathways of BP exposure to be further explored. To the best of our knowledge, this is the first study to conduct both an internal and external exposure assessment of BPs.