Hunting Metabolic Biomarkers for Exposure to Per- and Polyfluoroalkyl Substances: A Review.

Per- and polyfluoroalkyl substances (PFAS) represent a class of persistent synthetic chemicals extensively utilized across industrial and consumer sectors, raising substantial environmental and human health concerns. Epidemiological investigations have robustly linked PFAS exposure to a spectrum of adverse health outcomes. Altered metabolites stand as promising biomarkers, offering insights into the identification of specific environmental pollutants and their deleterious impacts on human health. However, elucidating metabolic alterations attributable to PFAS exposure and their ensuing health effects has remained challenging. In light of this, this review aims to elucidate potential biomarkers of PFAS exposure by presenting a comprehensive overview of recent metabolomics-based studies exploring PFAS toxicity. Details of PFAS types, sources, and human exposure patterns are provided. Furthermore, insights into PFAS-induced liver toxicity, reproductive and developmental toxicity, cardiovascular toxicity, glucose homeostasis disruption, kidney toxicity, and carcinogenesis are synthesized. Additionally, a thorough examination of studies utilizing metabolomics to delineate PFAS exposure and toxicity biomarkers across blood, liver, and urine specimens is presented. This review endeavors to advance our understanding of PFAS biomarkers regarding exposure and associated toxicological effects.

Use of different endpoints to determine the bioavailability of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in Sprague-Dawley rats.

Liver, fat (adipose tissue), blood, and feces are common endpoints used to determine the bioavailability of persistent organic pollutants (POPs). However, it is not known whether the bioavailability of each endpoints is comparable or whether there is a comprehensive endpoint that can be used for all congeners for the measurement of bioavailability. In this study, we observed the accumulation and distribution of 10 polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and 18 polychlorinated biphenyls (PCBs) in different organs of Sprague-Dawley (SD) rats and calculated the bioavailability based on feces, liver, and fat endpoints. Our results indicated that PCB 126, PCB 169, and 50% of PCDD/F congeners were mainly accumulated in the liver, with a bioavailability ranging from 28.9 to 50.6%. On the other hand, higher chlorinated (> 5 Cl) PCB congeners were mainly accumulated in adipose tissues, with a bioavailability ranging from 20.1 to 82.2%, while lower chlorinated (< 5 Cl) pollutants, such as 2,3,7,8-TeCDF, 2,3,7,8-TeCDD, 1,2,3,7,8-PeCDF, and PCB 28, 52, 77, 81, were likely metabolized over 36% in rats during the 8-week experimental period. If we considered metabolization (degradation) as a type of bioavailable process, then the fecal endpoint was a feasible option. However, if we considered the selective accumulation behavior of some congeners in different organs/tissues, then there was no single comprehensive endpoint suitable for all congeners. Lastly, female rats showed significantly higher PCDD bioavailability than male rats at low dose level (0.2 ng/100 g b.w./d); however, the difference in PCB bioavailability between female and male rats was not significant.

Effects of curcumin on the bioavailability of dioxin-like pollutants in rats.

The effects of curcumin on the bioavailability of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were investigated in Sprague-Dawley rats. Tetra- and penta-chlorinated PCDFs had the lowest bioavailability and hexa-chlorinated PCDD/Fs had the highest, while there was no obvious change in that of DL-PCBs. Curcumin markedly reduced the toxic equivalent (TEQ) of PCDD/Fs in rats, illustrating the potential to competitively inhibit absorption of PCDD/Fs by the epithelial cells of the small intestine due to the similar chemical structure (diphenyl) between curcumin and PCDD/Fs. Moreover, curcumin lowered the TEQ of DL-PCBs in the liver of male rats, but not female rats. The significant decrease in the bioavailability of PCDD/Fs and DL-PCBs demonstrates the potential detoxification mechanisms of curcumin.

Simultaneous detection of multiple hydroxylated polychlorinated biphenyls from biological samples using ultra-high-performance liquid chromatography with isotope dilution tandem mass spectrometry.

We established a method for the separation and detection of nine hydroxylated polychlorinated biphenyls in whole blood and urine samples using ultra high performance liquid chromatography coupled with electrospray negative ionization tandem mass spectrometry. Clean-up procedures involved a filtration step, and optimization involved a pretreatment step consisting of a simple liquid-liquid extraction using hydrated silica-gel chromatography (5%). Nine hydroxylated polychlorinated biphenyls were separated on an ultra high performance liquid chromatography HSS T3 column using a gradient elution program of 2 mmol ammonium formate aqueous solution (A) and methanol (B). Recovery ranged from 84.0 to 105.4% for the nine different hydroxylated polychlorinated biphenyls in urine with three spiked levels of 0.1, 1, and 2 ng and from 73.5 to 98.6% for the blood with spiked levels of 0.2, 1, and 2 ng. The relative standard deviations were <8.7% (n = 6), and the limits of detection in urine and whole blood for the nine hydroxylated polychlorinated biphenyls were in the range of 1.5-4 and 20-100 pg/g, respectively. This analytical method may enable the simultaneous detection of various hydroxylated polychlorinated biphenyls from complex tissue matrices.

[Toxicity of intragastrically administered N, N-dimethylformamide in female Wistar rats].

OBJECTIVE: To investigate the toxicity of intragastrically administered N, N-dimethylformamide (DMF) in female Wistar rats, and to provide experimental data for the overall evaluation of DMF toxicity under different ways of exposure. METHODS: Forty female Wistar rats weighing 150∼180 g were randomly divided into four groups: control group (treated with water) and three DMF exposure groups with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. After oral administration of DMF once a day for 14 consecutive days, the rats were weighed and sacrificed. The liver, kidney, brain, and uterus were weighed to calculate organ indices. The pathological changes in the liver were examined by HE staining. The protein expression of HSP70 in the liver, kidney, and brain was determined. Finally, peripheral lymphocytes were collected from the arteria cruralis to determine DNA damage by comet assay. RESULTS: Fourteen days after DMF exposure, the body weight and organ indices of the kidney, brain, and uterus showed no significant changes. However, the liver index showed concentration-dependent increase in all DMF exposed groups (3.52±0.21, 3.55±0.13, and 3.88±0.22 in the low-, medium-, and high-dose groups, respectively), as compared with the control group (3.24±0.28) (P < 0.05 or P < 0.01). The pathological damage in the liver also showed a concentration-dependent manner. Inflammatory cell infiltration and granular degeneration in centrilobular hepatocytes were observed in the high-dose group. No significant change in protein expression of HSP70 was observed in the liver, kidney, or brain of DMF-exposed rats (P > 0.05). DNA damage was induced by DMF, and the DNA percentage of lymphocyte comet tail, average tail length, and tail moment in exposed groups were all significantly increased as compared with the control group (P < 0.05 or P < 0.01). CONCLUSION: Gavaged DMF can induce liver injury and DNA damage in lymphocytes in rats 14 days after administration. There is no significant change in protein expression of HSP70 in the liver, brain, or kidney after DMF exposure.

Health risk assessment of lead for children in tinfoil manufacturing and e-waste recycling areas of Zhejiang Province, China.

Tinfoil manufacturing and electronic waste (e-waste) recycling remain rudimentary processes in Zhejing Province, China, which could account for elevated blood lead levels (BLLs) and health impacts on children. We assessed the potential health risks of lead in tinfoil manufacturing and e-waste recycling areas. 329 children in total aged 11-12 who lived in a tinfoil manufacturing area (Lanxi), an e-waste recycling area (Luqiao) and a reference area (Chun'an) were studied. Lead levels in children's blood were determined by inductively coupled plasma mass spectrometer (ICP-MS). Blood urea nitrogen (BUN), serum creatinine, serum calcium, δ-Aminolaevulinic acid (δ-ALA) and intelligence quotient (IQ) were also measured. Geometric mean of BLLs in Lanxi, Luqiao and Chun'an were 8.11 µg/dL, 6.97 µg/dL, and 2.78 µg/dL respectively, with 35.1%, 38.9% and 0% of children who had BLLs above 10 µg/dL. The BLLs in exposed areas were much higher than those in the control area. Lanxi children had higher creatinine and calcium than Chun'an children, and Luqiao children had higher δ-ALA and lower calcium than Chun'an children. No significant differences of IQ were observed between Lanxi, Luqiao and Chun'an, however a negative relationship between BLLs and IQ was shown for the study children. The results indicated that lead pollution from e-waste recycling and tinfoil processing appears to be a potential serious threat to children's health.

[Oxidative damage and immunotoxicity effect of people who exposed to electronic waste].

OBJECTIVE: To investigate the relationship between risk factors and the effects of antioxidation and immune function in adults who exposed to electronic waste( e-waste). METHODS: The exposed group was chosen from the people who lived in the e-waste disposing areas of Zhejiang province. The control group was chosen from people who lived in unpolluted area. Anticoagulation and coagulation peripheral venous blood samples were collected from 40 exposed persons (22 employees, 18 non-employees) and 36 exposed persons respectively. The oxidative, immune, Cd, Pb, Cr, Hg, and PCB indexes were detected. RESULTS: The contents of Cd, total PCB, MDA statistically increased in exposed group comparing with the control group (P < 0.05). The activity of SOD, GSH-Px, the percentage of helper/inducer T lymphocytes (CD4+) and the content of Cr in exposed group were less than those in the controlgroup (P < 0.05). CONCLUSION: Oxidative damage and immunotoxicity were observed in the group that lived in e-waste disposing areas. These effects were mainly related to the increase of Cd content or Cd and Pb contents in peripheral venous blood.

[Study on contamimation of endocrine disrupting chemicals in aquatic environment of Qiantang River].

OBJECTIVE: To study contamination of endocrine disrupting chemicals (EDCs) in aquatic environment of Qiantang River. METHODS: Carp vitellogenin (VTG) content in serum and ethoxyresorufin-o-deethylase (EROD) activity in liver of wild crucian, pesticide content including organic cholorine, organic phosphorus and pyrethroid in its muscle from 7 monitoring sites including Zhangtan (ZT), Jiekou (JK), Jiangjunyan (JJY), Yandongguan (YDG), Tonglu (TL), Fuyang (FY) and Yuanpu (YP) in Qiantang river were detected. And chemical analysis of water quality was carried on in four sites. RESULTS: EROD activity in crucian from ZT, JJY, FY and YP [(23.51 +/- 4.17), (16.79 +/- 7.39), (18.74 +/- 5.16), (18.65 +/- 8.86) nmol x g(-1) pro x min(-1), respectively] was significantly higher than that of control ((7.84 +/- 2.42) nmol x g(-1) pro x min(-1)), and VTG content in wild crucian from ZT, TL, FY and YP [(1.536 +/- 0.521), (16.404 +/- 13.579), (19.672 +/- 16.354) and (17.079 +/- 18.397)] microg/ml, respectively) was significantly higher than that of control [(0.400 +/- 0.099) (microg/ ml]. No significantly difference in biomarkers was observed between other site and control. From high to low, in total organophosphorus, it was followed as: TL, YDG, YP, FY, QZ, JK, JJY (EPN was up to 2695.64, 611.96 microg/kg in TL and YDG, respectively). In total organochlorine: TL, YP, YDG, FY, QZ, JK and JJY (tetradifon content in muscle of wild crucian from TL was up to 3962.17 microg/kg). For pyrethroid pesticides: TL, YDG, YP, ZT, JK, FY and JJY (alpha-tetramethrin and alpha-phenothrin was comparatively high in TL and YDG, up to 371.54, 239.62 microg/kg in the former, 416.23, 189.15 microg/kg in the latter, respectively). CONCLUSION: Aquatic environment of these sites including ZT, TL, FY and YP in Qiantang river received comparatively high EDCs, whose effects may be mainly due to pesticide pollution. Obvious organic contamination occurred in these sites including ZT, JJY, FY and YP. Changes of chemicals in water and EROD activity in fish test result are consistent with the actual contamination, while agricultural effluent discharges only affect the local River in the downstream. High PAH contamination in these sites such as ZT maybe lead to underestimation of estrogen effects, which was neglected easily, need be paid more attention to.

Distribution of PCDD/Fs, PCBs, PBDEs and organochlorine residues in children's blood from Zhejiang, China.

Concentrations and congener specific profiles of PCDD/Fs, PCBs, PBDEs and organochlorine residues were measured in 22 pooled blood samples representing 66 children from both polluted areas (E-waste recycling region) and case control areas in Zhejiang province, China. To our knowledge, this is the first report on these pollutants in the blood of Chinese children. The mean concentrations of [summation operator]PCDD/Fs, [summation operator]PCBs, [summation operator]PBDEs, HCB and pp'-DDE in pooled blood samples from polluted areas (Luqiao) were 206+/-157 pg g(-1) lipid, 40.6+/-7.01 ng g(-1) lipid, 32.1+/-17.5 ng g(-1) lipid, 14.6+/-20.1 ng g(-1) lipid and 108+/-21.8 ng g(-1) lipid, respectively. WHO-TEQ-2005 for PCBs and PCDD/Fs were 11.9+/-4.62 pg g(-1) lipid and 10.3+/-6.39 pg g(-1) lipid, respectively. The results showed that PCBs, PBDEs and organochlorine residues in the E-waste recycling area were significantly (P<0.001) higher than the case control areas. High levels of PCDD/Fs were detected in the case control area (Longyou), where Na-PCP had been widely sprayed to prevent snailborne schistosomiasis. The contamination levels and profiles were compared with those documented in previous publications.