ABSTRACT
Quaternary ammonium compounds (QACs), a large class of chemicals that includes high production volume substances, have been used for decades as antimicrobials, preservatives, and antistatic agents and for other functions in cleaning, disinfecting, personal care products, and durable consumer goods. QAC use has accelerated in response to the COVID-19 pandemic and the banning of 19 antimicrobials from several personal care products by the US Food and Drug Administration in 2016. Studies conducted before and after the onset of the pandemic indicate increased human exposure to QACs. Environmental releases of these chemicals have also increased. Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal. This work presents a critical review of the literature and scientific perspective developed by a multidisciplinary, multi-institutional team of authors from academia, governmental, and nonprofit organizations. The review evaluates currently available information on the ecological and human health profile of QACs and identifies multiple areas of potential concern. Adverse ecological effects include acute and chronic toxicity to susceptible aquatic organisms, with concentrations of some QACs approaching levels of concern. Suspected or known adverse health outcomes include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs' role in antimicrobial resistance has also been demonstrated. In the US regulatory system, how a QAC is managed depends on how it is used, for example in pesticides or personal care products. This can result in the same QACs receiving different degrees of scrutiny depending on the use and the agency regulating it. Further, the US Environmental Protection Agency's current method of grouping QACs based on structure, first proposed in 1988, is insufficient to address the wide range of QAC chemistries, potential toxicities, and exposure scenarios. Consequently, exposures to common mixtures of QACs and from multiple sources remain largely unassessed. Some restrictions on the use of QACs have been implemented in the US and elsewhere, primarily focused on personal care products. Assessing the risks posed by QACs is hampered by their vast structural diversity and a lack of quantitative data on exposure and toxicity for the majority of these compounds. This review identifies important data gaps and provides research and policy recommendations for preserving the utility of QAC chemistries while also seeking to limit adverse environmental and human health effects.
Subject(s)
COVID-19 , Disinfectants , Humans , Quaternary Ammonium Compounds/chemistry , Pandemics , Anti-Bacterial AgentsABSTRACT
The circular economy plays an important role in the preparation and recycling of polymers. Research groups in different fields, such as materials science, pharmaceutical and engineering, have focused on building sustainable polymers to minimize the release of toxic products. Recent studies focused on the circular economy have suggested developing new polymeric materials based on renewable and sustainable sources, such as using biomass waste to obtain raw materials to prepare new functional bio-additives. This review presents some of the main characteristics of common polymer additives, such as antioxidants, antistatic agents and plasticizers, and recent research in developing bio-alternatives. Examples of these alternatives include the use of polysaccharides from agro-industrial waste streams that can be used as antioxidants, and chitosan which can be used as an antistatic agent.
ABSTRACT
Objective To prepare a novel somatostatin receptor (SSTR) antagonist 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-JR11 (Cpa-c(D-Cys-Aph(Hor)-D-Aph(Cbm)-Lys-Thr-Cys)-D-Tyr-NH2 ) tracer and observe its biodistribution and microPET imaging in mice. Methods One ml HCl (0.05 mol/L) containing 68GaCl3(148 MBq) was added into 65μl NaAc (1 mol/L) and 4μg NOTA-JR11. The mixture reacted at 95 ℃ for 15 min, and then was purified with Sep-Pak? C18 Light column to obtain 68 Ga-NOTA-JR11. 68 Ga-NOTA-JR11 was subjected to quality control analysis including radiochemical purity and in vitro stability by radio-high performance liquid chromatography. Biodistribution of 68Ga-NOTA-JR11 (0.37 MBq) in BALB/c mice (n=9) at 5, 30, 60 min postinjection were observed (n=3 for each time point), and the percentage activity of injection dose per gram of tissue (％ID/g) was calculated. 68Ga-NOTA-JR11 (14.8 MBq) microPET imaging of BALB/c mice (n=1) at 60 min postinjection was observed. Results 68 Ga-NOTA-JR11 was obtained successfully within 15 min, with yielding rate of 90％, radiochemical purity of more than 99％, and specific activity of 6. 10 GBq/μmol. The tracer showed excellent stability ( radio-chemical purity:95％) in different buffers within 150 min. The biodistribution was basically consistent with microPET imaging results. 68 Ga-NOTA-JR11 was metabolized through the kidneys and had low uptake in the liver ((0.75±0.26) ％ID/g) at 60 min postinjection. Conclusions 68 Ga-NOTA-JR11 can be prepared rapidly, with high yielding rate and radiochemical purity. Biodistribution and imaging results provide basic information for the further study of somatostatin receptor imaging in neuroendocrine tumors.
ABSTRACT
Objective To study the reliability of 99Tcm-(hydrazinonicotinamide (HYNIC)-BMS-200261) (tricine) (trisodium triphenylphosphine-3,3',3"-trisulfonate (TPPTS)) as a radiotracer for protease activated receptor-1 (PAR-1) expression in breast cancer.Methods Fifteen nude mice bearing MDA-MB-435,MDA-MB-231 and MCF-7 human breast cancer xenografts (5 mice for each cell line) with different PAR-1 expression were used for 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) γ imaging,and tumor/non-tumor (T/NT) ratios were obtained with region of interest (ROI) technique.Afterwards,the biodistribution of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) was analyzed in tumor-bearing nude mice,and the radioactivity in tumor (percentage activity of injection dose per gram of tissue,％ID/g) was calculated.The immunostaining was performed to examine PAR-1 expression in tumor tissue and semi-quantitative analysis was used.One-way analysis of variance and Pearson correlation analysis were used to analyze data.Results At 2 h postinjection,the T/NT ratios were 3.03±0.32,2.27±0.25 and 1.51±0.13 respectively in nude mice bearing MDA-MB-435,MDA-MB-231 and MCF-7 xenografts;the tumor uptakes of 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS) were (1.03±0.15),(0.56±0.14) and (0.30±0.06) ％ID/g;PAR-1 expression levels were (17.22±2.71) ％,(10.78± 1.95) ％ and (2.80± 1.18) ％,respectively (F values:47.66,46.36,62.35,all P＜0.05).The T/NT ratios and tumor uptake of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) at 2 h post-injection were correlated with PAR-1 expression (r values:0.934 and 0.929,both P＜0.05).Conclusions 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) imaging could be a noninvasive and effective method for monitoring PAR-1 expression in human breast cancer.
ABSTRACT
T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy derived from T precursor cells. Morbidity of children accounted for 15%of ALL. Studies have found that PI3K-Akt-mTOR signaling pathway is associated with the occurrence of T-ALL, cell proliferation, cell apoptosis and drug resistance. The PI3K-Akt-mTOR signaling pathway inhibitors, which can target to inhibit T-ALL cell proliferation in the treatment of T-ALL children, plays an effective cytotoxic role. By shortening the duration of treatment, it can significantly improve the quality of life of children with T-ALL and reducing disease recurrence. It is a more effective way for traditional chemotherapy resistant T-ALL children patients.
ABSTRACT
Objective To synthesize 628F-Py-AMD3465,to investigate its biodistribution in mice and to perform the microPET/CT imaging on mice bearing human lung cancer cell (A549).Methods AMD3465 quaternary ammonium salt precursor was directly labeled with 18F,then 628F-Py-AMD3465 was synthesized through nucleophilic reaction,hydrolysis,neutralization and the product was purified using HPLC.The labeling yield and radiochemical purity were analyzed by HPLC.Fifteen Kunming mice were injected with 5.55 MBq of 628F-Py-AMD3465 and sacrificed at 5,20,40,60 and 120 min postinjection.The selected tissues were harvested and weighed,and the radioactivity in the tissues was measured by an automated γ-spectrometer.The ％ID/g was calculated.MicroPET/CT studies were performed on A549-bearing mice after injecting 6-18F-Py-AMD3465 through vena caudal.Paired t test was used.Results 6-18F-Py-AMD3465 was successfully synthesized with the labeling yield of (9.0±2.0)％,the total synthesis time was about 60 min,and the radiochemical purity was more than 98％.Biodistribution studies showed that the radiouptake was higher in the kidneys and bladder of normal mice,which demonstrated that 6-18 F-Py-AMD3465 was mainly excreted through the kidneys.Biodistribution in A549-bearing mice was similar to that in normal mice.The tumor/muscle ratio at 40 min was 5.0,but the radiouptake of the tumor was still lower than that of the normal lung:(8.05±0.35) ％ID/g vs (9.33±0.66) ％ID/g;t=5.26,P＜0.05.MicroPET/CT imaging showed that the high-uptake location of 6-18F-Py-AMD3465 in tumor-bearing mice was similar to the normal mice,and the tumor uptake reached the maximum level at 45 min post-injection (SUV 0.67).Conclusions 6-18F-Py-AMD3465 can be synthesized by a simple method.A lower uptake could be shown in the tumor compared to that in the lung and the tracer has limited diagnostic value for lung cancer.
