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.

Fluorinated liquid-crystal monomers in paired breast milk and indoor dust: A pilot prospective study.

Fluorinated liquid-crystal monomers (FLCMs), one class of emerging persistent, bioaccumulative and toxic (PBT) compounds, are widely used in liquid-crystal displays (LCDs). As a result, they have been found in the environment and serum from occupational workers. However, little is known about their occurrence in non-occupational exposing populations. Herein, we provided an evaluation of the health risks of FLCMs for infants based on breastfeeding exposure and dust ingestion. The detection frequencies (DF) of FLCMs in indoor dust and breast milk was 100 %, with median concentrations of 12.00 ng/g dry weight (dw) and 133.40 ng/g lipid weight (lw), respectively. 1-butoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene (BDPrB) was the predominant pollutant in indoor dust and human breast milk. Significant positive correlations were observed between the dust concentrations of seven FLCMs including BDPrB, and their breast milk concentrations (r = 0.275-0.660, P < 0.05). Further, associations were also found in some demographic and behavioral factors and concentrations of some FLCMs (P < 0.05). The highest EDI of ∑FLCMs was observed for infants who were < 1 month of age, with a median breast milk intake of 700.35 ng/kg bw/day, in which 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene (EDPrB), BDPrB, and 4'-[(trans, trans)-4'-butyl[1,1'-bicyclohexyl]-4-yl]-3,4-difluoro-1,1'-biphenyl (BBDB) collectively contributed 94.4 % of the total EDIs. Notably, the lactational intake of FLCMs was higher than that of some environmental pollutants (EPs). Overall, our results suggest higher exposure risks for infants and breastfeeding is the predominant exposure route for daily intake of FLCMs for infants.

Dietary Exposure and Health Risk of the Emerging Contaminant Fluorinated Liquid-Crystal Monomers.

Fluorinated liquid-crystal monomers (FLCMs) widely used in liquid crystal displays are considered to be a new generation of persistent, bioaccumulative, and toxic contaminants. They have been widely detected in the environment. However, little is known about their occurrence in food and human dietary exposure until now. Herein, we provided an evaluation of dietary exposure and health risks of FLCMs in the Chinese adult population based on the fifth and sixth total diet studies (TDSs). The detection frequencies of FLCMs in the two surveys were 90.5 and 99.5%, with concentrations ranging from not detected ∼72.6 µg/kg wet weight (ww) and ND ∼74.7 µg/kg ww, respectively. All TDS samples contained the multiresidue of FLCMs. The mean estimated daily intakes (EDIs) of FLCMs were 172.86 and 163.10 ng/kg bw/day in the fifth and sixth TDS, respectively. Meats, vegetables, and cereals contributed the most to the EDI of FLCMs. According to the threshold of toxicological concern (TTC) method, the EDIs of 1-fluoro-4-[2-(4-propylphenyl)ethynyl]benzene (4.56 and 3.26 ng/kg bw/day) and 2-fluoro-4-[4'-propyl-1,1'-bi(cyclohexyl)-4-yl]phenyl trifluoromethyl ether (3.12 and 3.28 ng/kg bw/day) were above their TTC value (2.5 ng/kg bw/day), suggesting their potential health risk. This is the first comprehensive national dietary exposure assessment of FLCMs.

Metabolic profiling of the fluorinated liquid-crystal monomer 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene.

1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene (EDPrB) is a typical fluorinated liquid-crystal monomer (LCM). LCMs contaminants are becoming increasingly concerning due to their potential persistence, bioaccumulation, toxicity, and broad prevalence in environmental and human samples. However, LCM metabolism is poorly understood. Herein, by introducing selected EDPrB into the appropriate liver microsomes in vitro, we examined the metabolic pathways of LCM in humans, rats, pigs, Cyprinus carpio, crucian carp, and Channa argus. A total of 20 species-dependent metabolites were identified and structurally elucidated by gas and liquid chromatography-high resolution mass spectrometry for the first time. Dealkylation, H-abstraction, and hydroxylation reactions are the primary metabolic pathways. Half of these in vitro metabolites were found in the urine, serum, and fecal samples of Sprague-Dawley rats exposed to EDPrB. Toxicity predictions indicate that 17 metabolites can be classified as toxic. According to the Ecological Structure Activity Relationships (ECOSAR), a number of metabolites exhibit equivalent or greater aquatic toxicity to that of EDPrB. Toxicity Estimation Software Tool (T.E.S.T.) predicts that some metabolites exhibit developmental toxicity and mutagenicity in rats. These findings suggest that biotransformation should be particularly emphasized, and more toxicological and monitoring studies should be performed to assess the ecological and human safety of LCMs.

Metabolic profiling of bisphenol A diglycidyl ether in vitro and in vivo.

Bisphenol A diglycidyl ethers (BADGE) is one class of human-made chemicals, and it is one of the most widely used raw materials for epoxy resins. As an active compound, BADGE undergoes biotransformation in vitro and in vivo. However, there is a limited understanding of the biotransformation of BADGE and toxicity studies on transformation products. We conducted comprehensive research on the metabolic transformation of BADGE in vitro and in vivo. The results showed that 12 metabolites and 7 metabolites were identified in vitro and in vivo, respectively. Four biotransformation products, including M1 (hydrolysis), M3 (dehydroxylation), M10 (carboxylation), and M11 (glucose conjugation), can be found in both in vitro and in vivo samples. The main metabolic pathways were hydroxylation, carboxylation, cysteine (Cys) conjugation, and glucose conjugation. Besides, our results suggested the existence of metabolic differences in BADGE between species and gender. Further, we investigated toxicities of BADGE metabolites in-silico. Importantly, some hydrolysis (M1, M2), hydroxylation (M7), and oxidation (M8) products showed similar or even higher potential toxicity than BADGE depending on the endpoint. These results enrich the biotransformation profiles of BADGE and provide useful information for understanding its biotransformation in humans and a reference for the comprehensive assessment for human health risk.

Bisphenol-diglycidyl ethers in paired urine and serum samples from children and adolescents: Partitioning, clearance and exposure assessment.

Bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and their derivatives are frequently used in food packaging materials. Some toxicological studies have shown that the endocrine-disrupting activities of these compounds are similar to or higher than those of bisphenol A (BPA), which may also adversely affect the growth and development of children and adolescents. Here, we investigated nine bisphenol-diglycidyl ethers (BDGEs) in 181 paired urine and serum samples from children and adolescents from Beijing to determine their partitioning, clearance and exposure levels. The results showed that nine BDGEs were detected in 181 urine and serum samples from children and adolescents from Beijing. Bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H2O) was the primary pollutant. The daily intake of ∑BDGEs was 15.217 ng/kg bw/day among children and adolescents in Beijing. The ranking of BDGEs in terms of renal clearance rate (CLrenal) in this study population was BADGE > BADGE·2H2O > BFDGE > bisphenol F bis(3-chloro-2-hydroxypropyl) glycidyl ether (BFDGE·2HCl) > bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) glycidyl ether (BADGE·HCl·H2O). In addition, the serum and urine ratios (S/U ratios) of BFDGE·2HCl, BADGE·2H2O, BFDGE, BADGE, and BADGE·HCl·H2O were higher than 1, indicating that these contaminants have a higher enrichment capacity in human blood. To our knowledge, this is the first study on the partitioning and renal clearance rate of BDGEs in paired urine and serum samples from children and adolescents.

Emerging Brominated Flame Retardants 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB) and Bis(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP) in Chinese Food and Their Health Implications.

2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP) have been frequently detected in the environment, whereas studies in food are scare. The European Food Safety Authority has requested data for their risk assessment. Herein, dietary exposure and hazard quotient (HQ) were studied based on the 5th (2009-2012) and 6th (2015-2018) Chinese total diet studies (TDSs). EHTBB was found in 61.1 and 75.9% of the two TDS sample sets, respectively. The concentrations of EHTBB in animal-derived food were higher than those in plant-derived food. The estimated daily intakes (EDIs) were 1.33 and 0.97 ng/kg bw/day, and vegetables contributed to 48.5 and 39.2% of the EDIs based on the 5th and 6th TDS, respectively. The dietary exposure to EHTBB was similar to that to hexabromocyclododecane, brominated diphenyl ether-209, and tetrabromobisphenol A (TBBPA). The HQ for EHTBB was similar to that for decabromodiphenyl ethane and surpassed that for TBBPA. Therefore, EHTBB warrants further study in food.

Bisphenol Analogues and Their Chlorinated Derivatives in Breast Milk in China: Occurrence and Exposure Assessment.

Concentrations of bisphenol A (BPA) and its analogues (together with their chlorinated derivatives are referred to as BPs) were measured in 181 breastmilk samples collected from 9 provinces in China in 2014. Twelve BP types were found. The BP concentrations ranged from not detected to 5.912 µg/L. BPA was the predominant BP, followed by bisphenol F (BPF) and bisphenol S (BPS). The mean BPA, BPF, and BPS levels were 0.444, 0.107, and 0.027 µg/L, respectively. Other BPs were sporadically detected in breastmilk samples. There were no differences (p > 0.05) in BPA, BPF, BPS, or total BP levels in the urban and rural regions or the northern and southern regions. BPA accounted for approximately 70% of the BPs and BPF accounted for more than 20% of the BPs in breast milk samples. The high contribution of BPF indicated that BPA analogues, not only BPA, should receive attention. The upper-bound daily intakes of BPs for infants 0-6 months old were 0.044-1.291 µg/kg bw/day. Despite the absence of tolerable daily intake data, attention should be paid not only on BPA but also BPF.

Determination of Nine Bisphenol-Diglycidyl Ethers in Human Breast Milk by Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry.

Because of their widespread use, and the mutagenicity and teratogenicity observed in in vitro studies, bisphenol-diglycidyl ethers (BDGEs) were suspected of posing health risks to humans, especially to infants. Quantifying exposure of BDGEs from breast milk is essential in assessing the potential health risks of these ubiquitous compounds to infants. However, there is no reported analytical method for the determination of BDGEs in breast milk. In this context, we developed a rapid and sensitive method based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to measure nine BDGEs in breast milk. The analytes were extracted with acetonitrile and fat was removed by freezing under -20 °C. The extracts were further purified by PRiME HLB solid-phase extraction (SPE) cartridge. The limits of detection (LODs) and quantification (LOQs) for the analytes were 0.033-0.500 and 0.100-1.500 µg L-1, respectively. The recoveries of BDGEs were ranged from 71.33% to 114.33%. Good method reproducibility regarding intra- and interday precision was observed, yielding relative standard deviations (RSDs) less than 11.81% and 10.83%, respectively. The proposed method was successfully applied to 20 breast milk samples. BADGE·2H2O, BADGE·HCl·H2O, BADGE·H2O, BADGE·HCl, BFDGE·2H2O, and BFDGE·2HCl were detected. BFDGE·2HCl was the dominant BDGE with detection rate of 65.0% and the concentration ranging from 0.4 to 1.0 µg L-1. This is the first report describing the occurrence of BDGEs in breast milk.