Chronic Toxicity Research Articles

Chronic Toxicity Investigations with Nilavembu Kudineer in Sprague-Dawley Rats

Chronic Toxicity Investigations with Nilavembu Kudineer in Sprague-Dawley Rats

Hypofractionated whole breast IMRT with HDR brachytherapy boost in early-stage breast cancer: Long-term results from a single-center

INTRODUCTION/OBJECTIVESThe addition of a boost to the lumpectomy bed after whole-breast (WB) radiotherapy plays a key role in the treatment of patients with breast cancer (BC). The clinical benefits of a boost with high-dose-rate brachytherapy (HDR-BT) after conventional fractionation is supported by a large body of evidence. However, few studies have described its outcomes after a hypofractionated scheme. MATERIALS AND METHODSWe included all patients treated with adjuvant WB-IMRT in 15 sessions followed by a single-session HDR-BT boost with local anesthesia on an outpatient basis. RESULTSBetween 2009 and 2017, 638 patients with early-stage BC were treated according to the aforementioned protocol after breast-conserving surgery. Median follow-up was 6 years (4–11). Despite the low incidence of side effects and their slightness, we did identify an impact of breast volume on the risk of acute radiodermatitis, fibrosis, pain and edema. However, we did not identify any relationship between the volume in cubic centimeters of the BT-implant with acute or long-term side effects. 2.2% patients had an actual local relapse, 2.4% a 2nd primary in the same breast and 2.39% were diagnosed with contralateral BC. Event-free survival at 11 years was 85.5% with an overall survival of 95.7%. CONCLUSIONAdjuvant hypofractionated whole-breast IMRT followed by a single dose HDR-BT boost has a low incidence of acute and chronic toxicity and excellent oncological outcomes. However, it may be worthwhile to intensify self-care protocols and surveillance in women with large breasts who may be at increased risk of side effects.

Evaluation of the chronic toxicity of bisphenol A and bisphenol AF to sea cucumber Apostichopus japonicus after long-term single and combined exposure at environmental relevant concentration

Bisphenols are emerging endocrine disrupting pollutant, and several studies have reported that they are already ubiquitous in various environmental matrices and intend to deposit in sediment. The primary sources of bisphenols are river and sewage discharge. Sea cucumber (Apostichopus japonicus), a typical deposit feeder, is one of the most important commercial marine species in Aisa. However, the effects of the bisphenol A (BPA) and its analogues bisphenol AF (BPAF) on sea cucumber was unclear. In this study, we carried out field survey in major sea cucumber farming areas in northern China, with the aim of determining which bisphenol analogue is the major bisphenol contamination in this aquaculture area. The results showed that the presence of BPAF was detected in four sampling sites (Dalian, Tangshan, Laizhou, and Longpan). The mean level of BPAF in Laizhou sediment samples was the highest which reached to 9.007 ± 4.702 μ g/kg. Among the seawater samples, the BPAF only have been detected in the samples collected at Longpan. (0.011 ± 0.003 μ g/L). Furthermore, we conducted an experiment to evaluate the single and combined toxicity of BPA and BPAF on sea cucumbers. The concentrations were informed by the findings based on the results of field research. (0.1, 1.0, and 10 μ g/L). After exposure, the body weight gain, and specific growth rate showed no significant changes (P > 0.05). We observed the histological alterations in respiratory tree of treated sea cucumbers including the fusion and detachment of lining epithelial tissue, and increase of lumen space. However, the catalase (CAT), malondialdehyde (MDA), and glutathione (GSH) activity was not significantly changed (P > 0.05). We evaluated the effects of BPA and BPAF through calculating the integrated biomarker response index (IBR), and the results indicated that the toxicity of combined treatment was higher than single treatment. Additionally, BPAF exposure to A. japonicus was more toxic than BPA.

Investigating pharmaceuticals and personal care products in Musi River: A exploratory study in Hyderabad, India

This study investigated the presence of 46 pharmaceuticals and personal care products (PPCPs), including antibiotics, anti-inflammatory, antifungal, surfactant, antidepressants, and anticonvulsants, in wastewater samples collected from 11 sites along the Musi River in Hyderabad, India. These samples were obtained from diverse points along the river, representing urban, industrial, and hospital-related sources. This strategic selection ensures a comprehensive assessment of water quality, covering areas of varying population density and industrial activity. The samples were extracted for PPCPs using solid-phase extraction and quantified using ultra-performance liquid chromatography-tandem mass spectrometry in multiple reaction mode. Of the 46, 16 target analytes were detected at concentrations ranging from 0.01 ± 0.001 μg/L (for fluoxetine) to 19.295 ± 4.16 μg/L (for ciprofloxacin). An ecological risk assessment was conducted in terms of risk quotient (RQ) for acute and chronic effects for three trophic levels of aquatic organisms (algae, fish, and invertebrates) for each detected contaminant at every site. In the case of acute toxicity, high RQ values (>>1) were obtained for the antibiotics, naproxen, diclofenac, caffeine, fluconazole, propyl paraben, fluoxetine, and benzalkonium chloride C-12. In the case of chronic toxicity, high RQ values (>>1) were estimated for some of the commonly used PPCPs. This study aimed to investigate the contamination levels of PPCPs in various wastewater discharge points along the Musi River in Hyderabad, a densely populated urban center with a population density of up to 45,000/sq km. Additionally, the research conducted an ecotoxicological risk assessment to evaluate the risk posed by these pollutants to three trophic levels (algae, fish, and invertebrates) using RQ analysis. Notably, this study represents the first attempt to conduct such an assessment in this region, providing valuable insights into environmental health and pollution management.

Partial-accelerated irradiation with stereotactic radiotherapy at a dose of 30Gy in 5fractions in early breast cancer.

To evaluate feasibility of accelerated partial breast irradiation (APBI) using stereotactic radiotherapy (SBRT) Thirty Gy delivered in 5 fractions for patients with early breast cancer. Between January 1st, 2018, and December 31s, 2022, we conducted 117 treatments for patients with early-stage breast cancer. All patients underwent conservative surgery followed by APBI using stereotactic external beam radiotherapy. We analyzed local, regional, distant control, overall survival, toxicity, and cosmetic outcomes. The average age was 62years. 21.3% ductal and 78.7% invasive carcinomas. Regarding the PTV volume, the median was 198.8 cc (38-794cc). Treatments were completed in all cases. The median follow-up period was of 21months (1-62 months). Regarding acute toxicity, no Grade 3-4 toxicities were recorded. One patient experienced Grade 2 neuropathic pain. One patient developed subacute fibrosis and two patients developed telangiectasia as subacute and chronic toxicity. Cosmetic results were "good" or "very good" in 96.3% of cases. None of the patients relapsed at any level (local, regional, or distant) and overall survival during follow.up was 100%. APBI with SBRT 30Gy in 5 fractions in early-stage breast cancer is a feasible technique, very-well tolerated and has excellent oncologic and cosmetic outcome during our follow-up period.

21 Gy single fraction prostate HDR brachytherapy: 5-year results of a single institution prospective pilot study

PURPOSETo present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. METHODS AND MATERIALSPatients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. Eligible patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients underwent trans-rectal ultrasound-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy to a dose of 21 Gy. The primary endpoint was grade ≥ 2 urinary/GI toxicity rates. RESULTSTwenty-six patients were enrolled with a median follow up of 5.1 years and median age of 64 years. 88.5% of patients had T1 disease, 15.4% had Gleason score 6 (84.6% Gleason 7), and median pre-treatment PSA was 5.0 ng/mL. Acute and chronic grade ≥ 2 urinary toxicity rates were 38.5% and 38.5%, respectively. There were no grade ≥ 2 acute or chronic GI toxicities. Six (23.1%) patients experienced biochemical failure, six (23.1%) patients experienced radiographic local failure, and five (19.2%) patients had biopsy-proven local failure. No patients developed regional lymph node recurrence or distant metastasis. 5-year overall survival and cause-specific survival were 96.2% and 100%, respectively. CONCLUSIONS21 Gy single fraction HDR brachytherapy was associated with modestly higher-than-anticipated chronic urinary toxicity, as well as high biochemical and local failure rates. The results from this prospective pilot study do not support the use of this regimen in standard clinical practice.

Renal toxicity of ifosfamide in children with cancer: an exploratory study integrating aldehyde dehydrogenase enzymatic activity data and a wide-array urinary metabolomics approach

BackgroundIfosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity.MethodsThe IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified.ResultsThe 15 participants received a median total ifosfamide dose of 59 g/m2 (range: 24–102), given over a median of 7 cycles (range: 4–14). All children had acute proximal tubular toxicity during chemotherapy that was reversible post-cycle, seen with both conventional assays and NMR. After a median follow-up of 31 months, 8/13 children presented overall chronic toxicity among which 7 had decreased glomerular filtration rate. ALDH enzymatic activity showed high inter- and intra-individual variations across cycles, though overall activity looked lower in children who subsequently developed chronic nephrotoxicity. Concentrations of ifosfamide and metabolites were similar in all children.ConclusionsAcute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.

Beauvericin and enniatin B mycotoxins alter aquatic ecosystems: Effects on green algae

Myxotoxins can contaminate algal-based products and arrive to the food chain to consumers producing chronic toxicity effects. Here, we studied phytotoxicity of mycotoxins, beauvericin (BEA) and ennaitin B (ENN B) in four phytoplankton strains: Acutodesmus sp., Chlamydomonas reinhardtii, Haematococcus pluvialis, and Monoraphidium griffithii, which are all green algae. It was tested the capacity of clearing the media of BEA and ENN B at different concentrations by comparing nominal and measured quantifications. Results revealed that Acutodesmus sp. and C. reinhardtii tended to flow up and down growth rate without reaching values below 50% or 60%, respectively. On the other hand, for H. pluvialis and M. griffith, IC50 values were reached. Regarding the clearance of media, in individual treatment a decrease of the quantified mycotoxin between nominal and measured values was observed; while in binary treatment, differences among both values were higher and more noted for BEA than for ENN B.

Emerging insights into the impacts of heavy metals exposure on health, reproductive and productive performance of livestock.

Heavy metals, common environmental pollutants with widespread distribution hazards and several health problems linked to them are distinguished from other toxic compounds by their bioaccumulation in living organisms. They pollute the food chain and threaten the health of animals. Biologically, heavy metals exhibit both beneficial and harmful effects. Certain essential heavy metals such as Co, Mn, Se, Zn, and Mg play crucial roles in vital physiological processes in trace amounts, while others like As, Pb, Hg, Cd, and Cu are widely recognized for their toxic properties. Regardless of their physiological functions, an excess intake of all heavy metals beyond the tolerance limit can lead to toxicity. Animals face exposure to heavy metals through contaminated feed and water, primarily as a result of anthropogenic environmental pollution. After ingestion heavy metals persist in the body for an extended duration and the nature of exposure dictates whether they induce acute or chronic, clinical or subclinical, or subtle toxicities. The toxic effects of metals lead to disruption of cellular homeostasis through the generation of free radicals that develop oxidative stress. In cases of acute heavy metal poisoning, characteristic clinical symptoms may arise, potentially culminating in the death of animals with corresponding necropsy findings. Chronic toxicities manifest as a decline in overall body condition scoring and a decrease in the production potential of animals. Elevated heavy metal levels in consumable animal products raise public health concerns. Timely diagnosis, targeted antidotes, and management strategies can significantly mitigate heavy metal impact on livestock health, productivity, and reproductive performance.

Investigation of Potential Protective effects of Betanin on experimental Monosodium Glutamate–induced toxicity in Elderly rats

This study was conducted to investigate the protective effects of Betanin active ingredient in red beetroot plant (Beta vulgaris) in elderly rats exposed to chronic toxicity of monosodium glutamate (MSG). A total of 48 elderly rats were randomly divided into 4 different groups. At the end of the 28–day study, the rats were sacrificed under deep anesthesia. Total antioxidant capacity (TAC), total oxidant capacity (TOC), paraoxonase (PON), thiol, malondialdehyde (MDA), and nitric oxide (NO) levels were investigated in rat blood serum using the spectrophotometric method. Oxidative Stress Index (OSI) was calculated by dividing TOC by TAC. Total bilirubin was measured with the colorimetric method using an ELISA kit. Liver tissues were stained with hematoxylin–eosin (HE) for histopathological examination. The difference in serum levels of TAC, TOC, OSI, PON, MDA, and thiol was statistically significant between the groups (P<0.05). The difference in serum levels of NO and total bilirubin was not statistically significant between the groups (P>0.05). The analysis of histopathological findings revealed uncommon mild hydropic degeneration in the MSG group and almost normal histological appearance in the MSG+Betanin group. This study demonstrated that betanin could increase the antioxidant effect and reduce the histopathological damage caused by MSG.

Dermoscopy of Chronic Radiation-Induced Dermatitis in Patients with Head and Neck Cancers Treated with Radiotherapy.

Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future.

Environmental-related doses of afidopyropen induced toxicity effects in earthworms (Eisenia fetida)

Afidopyropen has high activity against pests. However, it poses potential risks to the soil ecology after entering the environment. The toxicity of afidopyropen to earthworms (Eisenia fetida) was studied for the first time in this study. The results showed that afidopyropen had low level of acute toxicity to E. fetida. Under the stimulation of chronic toxicity, the increase of reactive oxygen species (ROS) level activated the antioxidant and detoxification system, which led to the increase of superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. Lipid peroxidation and DNA damage were characterized by the increase of malondialdehyde (MDA) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) contents. Meanwhile, the functional genes SOD, CAT, GST, heat shock protein 70 (HSP70), transcriptionally controlled tumor protein (TCTP), and annetocin (ANN) played a synergistic role in antioxidant defense. However, the comprehensive toxicity of high concentration still increased on the 28th day. In addition, strong histopathological damage in the body wall and intestine was observed, accompanied by weight loss, which indicated that afidopyropen inhibited the growth of E. fetida. The molecular docking revealed that afidopyrene combined with the surface structure of SOD and GST proteins, which made SOD and GST become sensitive biomarkers reflecting the toxicity of afidopyropen to E. fetida. Summing up, afidopyropen destroys the homeostasis of E. fetida through chronic toxic. These results provide theoretical data for evaluating the environmental risk of afidopyropen to soil ecosystem.

Toward a Mechanism-Driven Integrated Framework to Link Human Exposure to Multiple Toxic Metal(loid) Species with Environmental Diseases.

The ongoing anthropogenic pollution of the biosphere with As, Cd, Hg and Pb will inevitably result in an increased influx of their corresponding toxic metal(loid) species into the bloodstream of human populations, including children and pregnant women. To delineate whether the measurable concentrations of these inorganic pollutants in the bloodstream are tolerable or implicated in the onset of environmental diseases urgently requires new insight into their dynamic bioinorganic chemistry in the bloodstream-organ system. Owing to the human exposure to multiple toxic metal(loid) species, the mechanism of chronic toxicity of each of these needs to be integrated into a framework to better define the underlying exposure-disease relationship. Accordingly, this review highlights some recent advances into the bioinorganic chemistry of the Cd2+, Hg2+ and CH3Hg+ in blood plasma, red blood cells and target organs and provides a first glimpse of their emerging mechanisms of chronic toxicity. Although many important knowledge gaps remain, it is essential to design experiments with the intent of refining these mechanisms to eventually establish a framework that may allow us to causally link the cumulative exposure of human populations to multiple toxic metal(loid) species with environmental diseases of unknown etiology that do not appear to have a genetic origin. Thus, researchers from a variety of scientific disciplines need to contribute to this interdisciplinary effort to rationally address this public health threat which may require the implementation of stronger regulatory requirements to improve planetary and human health, which are fundamentally intertwined.

The presence of erionite in North American geologies and the estimated mesothelioma potency by region

Objective Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers. Materials and Methods Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined. Results and Discussion The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5. Conclusion The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).

Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-β1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis.

Renal fibrosis is a complex pathological process that contributes to the development of chronic kidney disease due to various risk factors. Conservative treatment to curb progression without dialysis or renal transplantation is widely applicable, but its effectiveness is limited. Here, the inhibitory effect of the novel peptide DR3penA (DHα-(4-pentenyl)-AlaNPQIR-NH2), which was developed by our group, on renal fibrosis was assessed in cells and mice with established fibrosis and fibrosis triggered by transforming growth factor-β1 (TGF-β1), unilateral ureteral obstruction, and repeated low-dose cisplatin. DR3penA preserved renal function and ameliorated renal fibrosis at a dose approximately 100 times lower than that of captopril, which is currently used in the clinic. DR3penA also significantly reduced existing fibrosis and showed similar efficacy after subcutaneous or intraperitoneal injection. Mechanistically, DR3penA repressed TGF-β1 signaling via miR-212-5p targeting of low-density lipoprotein receptor class a domain containing 4, which interacts with Smad2/3. In addition to having good pharmacological effects, DR3penA could preferentially target injured kidneys and exhibited low toxicity in acute and chronic toxicity experiments. These results unveil the advantages of DR3penA regarding efficacy and toxicity, making it a potential candidate compound for renal fibrosis therapy.

Immunosuppression, growth retardation, and transcriptomic profile alterations induced by chronic copper toxicity in Clarias gariepinus: The ameliorative effect of zinc oxide nanoparticles

This study was designated to look into the toxicological effects of long-term exposure of African catfish (Clarias gariepinus) to a heavy metal (copper) on the growth, hematology, immune-antioxidant functions and their regulating genes, and resistance to Aeromonas sobria. Furthermore, the efficiency of dietary zinc oxide nanoparticles (ZNPs) to ameliorate copper toxicity was assessed. Fish (n=300: average body weight: 90.56±0.20 g) were equally allocated into six groups in five replicates (10 fish/replicate; 50 fish/ group) for 60 days at a water temperature of 25 ± 1.2 ◦C. Three diets were formulated with varying ZNPs levels: control (0 mg kg−1), ZNPs20 (20 mg kg−1), and ZNPs30 (30 mg kg−1), with actual zinc concentrations of 45, 65, and 75 mg kg−1, respectively. The experimental groups were named, control, ZNPs20, and ZNPs30 groups which were fed on the control, ZNPs20, and ZNPs30 diets, respectively without copper exposure. Additionally, the CuCL2, CuCL2+ZNPs20, and CuCL2+ZNPs30 groups were received the same feeding regime as the control, ZNPs20, and ZNPs30 groups, respectively and exposed to copper chloride, CuCL2 (10 mg L−1). At the end of the exposure trial (60 days), all experimental groups were challenged with 0.2 mL of A. sobria (1×108 CFU mL−1) and the mortalities were recorded daily for additional 7 days. The results displayed that copper exposure resulted in lower growth metrics and survivability. The final body weight, weight gain, feed intake, and survivability were reduced in the CuCL2 group by 39.29%, 23.79%, 63.37%, and 20%, respectively with increasing the feed conversion ratio by 52.13% compared to the control group. In addition, reduced hematological (red blood cells (58.40%), hemoglobin (48.11%), packed cell volume (40.59%), white blood cells (46.85%), total proteins (43.12%), albumin (41.98%), and globulin (44.23%)), immune (lysozymes (59.74%), complement 3 (41.89%), nitric oxide (57.14%), and phagocytic activity (38.75%)), and antioxidant parameters (glutathione peroxidase (82.95%), catalase (74.08%), and superoxide dismutase (48.59%)), as well as higher oxidative (malondialdehyde) (200.30%) indicator were observed in the CuCL2 group compared to the control group. A down-regulation of the antioxidant (glutathione peroxidase-1) and immune (lysozyme-G, lysozyme-C, transforming growth factor-beta, and myeloperoxidase) genes with up-regulation of the inflammatory cytokines (interleukin-1ß, interleukin-8, tumor necrosis factor-alpha, nuclear factor kappa β, and Toll-like receptor 5) was noticed in the CuCL2 group. In addition, the survivability of the CuCL2 group during A. sobria challenge was reduced (25%) compared to the control group. Noticeably, ZNPs diets modulated the growth, survival, and antioxidant/immune functions and their associated genes of the copper-exposed fish. In addition, ZNPs increased the resistance of the copper-exposed fish to A. sobria challenge. ZNPs diets especially at 30 mg kg−1 level proposed a promising feed additive for mitigating the stress consequences of copper exposure in African catfish.

A Comprehensive Review of the Nutritional Composition and Toxicological Profile of Date Seed Coffee (Phoenix dactylifera)

Approximately 8 million tons of dates (Phoenix dactylifera) are produced globally each year. The seeds of the fruit, which make up 10–15% of its weight, are typically discarded. Date seed coffee is a sustainable food system innovation rooted in the traditions of high date-producing regions. Dating back to the late 19th century, date seed coffee has evolved from a historical coffee substitute to a modern caffeine-free alternative. Date seed coffee has a long history of consumption in the European Union (EU). This indicates that it may not require novel food authorization. The composition of date seeds is evaluated in this review and a toxicological risk assessment for date seed coffee is conducted. Subchronic studies show that consuming date seed or date seed coffee has no adverse effects. Therefore, currently unavailable chronic toxicity, carcinogenicity, and reproductive toxicity studies may be unnecessary. However, for a comprehensive evaluation, it is recommended to conduct an in vitro mutagenicity test. This review provides information on the safety of date seed coffee and highlights the need for further research.

Assessing the photo-activation efficiency of aminopolycarboxylate iron complex mixtures for effective sulfamethoxazole degradation in a pilot-scale UVA-LED photoreactor

This study focused on the degradation of antibiotic sulfamethoxazole (SMX), through the UVA-LED photo-activation of aminopolycarboxylate-based iron complexes in a pilot-scale photoreactor. Fe3+-EDDS, Fe3+-NTA, and a combination of both complexes Fe3+-EDDS and Fe3+-NTA were studied in simulated tap water (TW) and simulated secondary effluent (SE) from a municipal wastewater treatment plant (MWWTP). In TW, 40% SMX degradation was reached after 60 min, with different concentration profiles due to absorption characteristics of each complex. Combining Fe3+-EDDS and Fe3+-NTA an initial rapid SMX degradation was observed followed by a slower phase, improving SMX degradation with respect to each complex separately. In SE and despite presenting similar kinetics, SMX degradation was lower than in TW, due to the presence of organic matter in the water matrix. Moreover, the Fe3+-EDDS and Fe3+-NTA mixture improved SMX degradation with increasing iron concentration. This improvement was attributed to reduced dissolved organic carbon (DOC) from NTA and the lower molar absorption coefficient of Fe3+-NTA. Higher EDDS ratios led to faster complex degradation but did not significantly enhance SMX removal. Conversely, higher NTA ratios reduced SMX degradation. In summary, this study revealed a synergistic effect between Fe3+-EDDS and Fe3+-NTA in SMX degradation. Considering the cost difference between EDDS and NTA, using both compounds offers technical and economic advantages. All treatments reduced chronic toxicity in Selenastrum capricornutum.

Effect of Tanshinone IIA versus Tanshinone IIA loaded nanocarriers on folic acid induced chronic toxicity of renal convoluted tubules in rats

Effect of Tanshinone IIA versus Tanshinone IIA loaded nanocarriers on folic acid induced chronic toxicity of renal convoluted tubules in rats

Persulfate-Based Advanced Oxidation Process for Chlorpyrifos Degradation: Mechanism, Kinetics, and Toxicity Assessment.

Persulfate-based advanced oxidation process has been proven to be a promising method for the toxic pesticide chlorpyrifos (CPY) degradation in wastewater treatment. However, due to the limitation for the short-lived intermediates detection, a comprehensive understanding for the degradation pathway remains unclear. To address this issue, density functional theory was used to analyze the degradation mechanism of CPY at the M06-2X/6-311++G(3df,3pd)//M06-2X/6-31+G(d,p) level, and computational toxicology methods were employed to explore the toxicity of CPY and its degradation products. Results show that hydroxyl radicals (·OH) and sulfate radicals (SO4•-) initiate the degradation reactions by adding to the P=S bond and abstracting the H atom on the ethyl group, rather than undergoing α-elimination of the pyridine ring in the persulfate oxidation process. Moreover, the addition products were attracted and degraded by breaking the P-O bond, while the abstraction products were degraded through dealkylation reactions. The transformation products, including 3,5,6-trichloro-2-pyridynol, O,O-diethyl phosphorothioate, chlorpyrifos oxon, and acetaldehyde, obtained through theoretical calculations have been detected in previous experimental studies. The reaction rate constants of CPY with ·OH and SO4•- were 6.32 × 108 and 9.14 × 108 M-1·s-1 at room temperature, respectively, which was consistent with the experimental values of 4.42 × 109 and 4.5 × 109 M-1 s-1. Toxicity evaluation results indicated that the acute and chronic toxicity to aquatic organisms gradually decreased during the degradation process. However, some products still possess toxic or highly toxic levels, which may pose risks to human health. These research findings contribute to understanding the transformation behavior and risk assessment of CPY in practical wastewater treatment.