Terms Of Toxicity Research Articles

KV-CBCT-Guided Daily Adaptation Improves Target Coverage and Spares Normal Tissue for Accelerated Partial Breast Irradiation

Linear accelerator based accelerated partial breast irradiation (APBI) in early-stage breast cancer necessitates a reduction in non-target breast tissue to decrease long term toxicity and adverse cosmetic outcome. In particular, lumpectomy cavity seromas may decrease in size and deform in shape during the course of short course APBI. Online adaptive RT (oART) offers considerable prospect for treating mobile targets through pendulous breast anatomy. However, there are limited studies outlining the methods and outcomes of CBCT-based oART for APBI. Here we present a retrospective, single institutional study analyzing the treatment process for patients receiving stereotactic kV-CBCT guided oART APBI. Fourteen patients were treated to 30 Gy in 5 fractions for a total of 70 fractions. Time between simulation and treatment, change in gross tumor volume (GTV), and differences in DVH metrics with adaption were analyzed. The Wilcoxon paired, non-parametric test was utilized to test for DVH metric differences between the scheduled plans (initial plans recalculated on daily CBCT anatomy) and treated plans, which were either the scheduled or adapted plan (initial plans re-optimized using daily anatomy), depending on the preference of the treating physician or physicist. Median (inter-quartile range) time from simulation to first treatment was 28 days (21-33 days). During this same time, GTV volume reduced to 72.5% (57.8-87.3%) of the simulation lumpectomy cavity volume. Adaptive treatments required 31.1 min (27.2-37.1 min) from start of CBCT to treatment session end. Table 1 summarizes differences between scheduled and treated plan metrics for 70 fractions, 62 (89%) of which were treated adaptively and 8 (11%) of which were treated using the scheduled plan. Significant improvement in prescription planning target volume coverage (p = 0.003), significant reduction in 5/6 organ-at-risk metrics evaluated (p ≤ 0.003), and significant improvement in conformity index and high dose spillage (p ≤ 0.001) were realized with adaption. Table 1: Scheduled versus treated plan metrics. APBI using oART decreased most organs at risk DVH metrics, improved plan quality metrics, and increased target coverage, justifying the use of kV-CBCT-guided oART for APBI.

Involved Site Radiotherapy in HPV Positive Oropharyngeal Cancer: Patterns of Failure Analysis Across Prospective De-Escalation Trials

HPV-associated oropharyngeal cancers (HPV+OPC) have a favorable prognosis with ongoing efforts to reduce long term toxicity while maintaining oncologic outcomes. One method under investigation includes lowering the elective radiation dose or in some cases omitting radiation to elective lymphatic nodal stations. Furthermore, pre-clinical evidence demonstrates that elective nodal irradiation blunts the anti-tumor immune response in head and neck cancer. This is a pooled secondary analysis reporting patterns of failure in patients (pts) with HPV+OPC enrolled on consecutive induction chemo- or chemoimmunotherapy (IC) based response-adaptive de-escalation trials and treated with involved-site radiotherapy (ISRT). Pts treated on two prospective phase II trials as well as on a prospective cohort registry were included for analysis. Pts with ≥ 50% response to IC based on RECIST 1.1 who received de-escalated definitive radiotherapy (RT) or concurrent chemoradiation (CRT) with ISRT were evaluable. Pts with locally advanced low risk or high-risk HPV+OPC (LR and HR, respectively) were eligible for enrollment. Pts were considered to have HR if at least one of the following criteria was met: T4 primary, N2c-N3 disease (AJCC 7th ed.), or > 10-20 pack years smoking. In the first trial, pts with ≥ 50% response to IC received RT to gross disease plus a 1.5 cm margin (PTV1) and to the next echelon of uninvolved nodes (PTV2). Pts with LR received 50 Gy in 2 Gy daily fractions without chemotherapy; pts with HR received 30 Gy in 1.5 Gy BID fractions to PTV2 with a 15 Gy sequential boost to PTV1 with CRT. In the subsequent trial, pts with ≥ 50% response received RT to PTV1 alone to 50 Gy in 2 Gy daily fractions; concurrent CRT was included if pts had HR. Survival was estimated using the Kaplan Meier method for progression free survival (PFS), locoregional PFS (LRPFS), and overall survival (OS). Patterns of failure analysis was performed by comparing RT plans to radiographic surveillance scans. Of 172 evaluable pts, 119 (69.2%) achieved a ≥ 50% response to IC and received definitive ISRT. 45 (37.8%) pts evaluated received RT to gross disease only plus margin without the next nodal echelon included. With a median follow up of 46 (IQR 34-65) months, 3-year PFS, LRPFS, and OS with their 95% confidence intervals were 96.2% (90.1-98.5%), 97.1% (91.1-99.0%), and 96.2% (90.3-98.6%), respectively. All locoregional failures were in-field and in the high dose region. No failures were observed in the RT omitted neck. This prospective experience demonstrates feasible volume de-escalation using IC response-based selection with progressively smaller elective volumes over time. Notably, despite a marked reduction in elective treatment volume, there were no regional out-of-field failures. IC may allow for selection of pts with favorable tumor biology and microscopic disease sterilization in the regional nodes. Further efforts at elective nodal de-escalation are needed.

Single Institute Experience with MRI-Guided Adaptive Brachytherapy for Locally Advanced Cervix Cancer: Long Term Outcomes and Toxicity Analysis

We report over 10 years' experience of MRI-guided adaptive brachytherapy (MRIGABT) in locally advanced cervix cancer (LACC). A total of 162 patients with LACC FIGO stage IB-IVB were treated at our institute between 2010 and 2020. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m², 5 cycles, 1 day per cycle, 45-50.4 Gy external beam radiotherapy (EBRT) in 1·8-2 Gy fractions, followed by MRIGABT. Target volume definition and dose reporting for MRIGABT was according to GEC-ESTRO recommendations. MRIGABT dose prescription was according to our institutional practice. Overall survival (OS) and disease-free survival (DFS) were the primary endpoints. Kaplan-Meier estimates were calculated for OS and DFS at 2, 5 and 10-years. Organ-specific late toxicity grade ≥3 (≥G3) (CTCAEv5.0) was reported, alongside rates of bowel fistula, stricture, and perforation. Using logistic regression, we explored the relationship between EQD2 D2cc bladder and ≥G3 genitourinary (GU) toxicity. We compared patient proportions developing ≥ G3 GU toxicity in those who received EQD2 ≥85 Gy versus <85 Gy. We examined the following predictors of ≥G3 gastrointestinal (GI) toxicity: EQD2 dose (≥65 Gy versus <65 Gy), pre-existing bowel conditions, nodal boost, and extended field EBRT. Median follow up was 4.7 years (IQR 3.3-7.1 years). Median EBRT dose was 50.4 Gy (IQR 50.4-50.4 Gy); 91% received chemotherapy. Median high-risk clinical target volume (HRCTV) was 23.6 cm3 (IQR 16.6-31.3 cm3). Median doses were as follows; D90 HRCTV 88.9 Gy EQD210 (IQR 84.1-91.3 Gy), median D2cc bladder 81.6 (IQR 76.9-85.7 Gy), rectum 62.2 (IQR 57.9-65.3 Gy), sigmoid 67.4 (IQR 60.8-71.1 Gy), and bowel 55 (IQR 49.9-63.2 Gy), (all EQD23). The 2, 5 and-10-year OS were 98%, 80% and 75%. The 2, 5 and 10-year DFS were 98%, 75% and 60%. Late toxicity ≥G3 was 9% GU, 6% GI and 3% vaginal. There was a significant relationship between EQD2 and ≥G3 GU toxicity (OR: 1.11, 95% CI: 1.01-1.25; P = 0.04). When comparing those who received EQD2≥ 85Gy versus <85Gy, higher doses were associated with a greater proportion of ≥G3 GU toxicity (13% vs 6%). No significant predictors of ≥ G3 GI toxicity were observed. We observed excellent LC and OS. A significant relationship was found between EQD2 >85 Gy and bladder toxicity, although ≥G3 toxicity was low. We did not identify predictors of bowel toxicity. New predictors of bowel toxicity are required. Mean EBRT dose, D1.0 cc rectum, sigmoid and bowel are being investigated further.

Elicitation of E-waste (acrylonitrile-butadiene styrene) enriched soil bioremediation and detoxification using Priestia aryabhattai MGP1

Given the rise in both usage and disposal of dangerous electronics, there is a catastrophic rise in assemblage of electronic waste (e-waste). E-waste including various plastic resins are among the most frequently discarded materials in electronic gadgets. In current digital era, managing e-waste has become universal concern. From the viewpoint of persisting lacuna of e-waste managing methods, the current study is designed to fabricate an eco-friendly e-waste treatment with native soil bacteria employing an enrichment culture method. In the presence of e-waste, indigenous soil microbes were stimulated to degrade e-waste. Microbial cultures were isolated using enrichment medium containing acrylonitrile-butadiene styrene (ABS) as the primary carbon source. Priestia aryabhattai MGP1 was found to be the most dominant e-polymer degrading bacterial isolate, as it was reported to degrade ABS plastic in disposed-off television casings. Furthermore, to increase degradation potential of MGP1, Response Surface Methodology (RSM) was adopted which resulted in optimized conditions (pH 7, shaking-speed 120 rpm, and temperature 30 °C), for maximum degradation (18.88%) after 2 months. The structural changes induced by microbial treatment were demonstrated by comparing the findings of Field emission scanning electron microscopy (FESEM) images and Fourier Transform Infrared (FTIR) spectra confirming the disappearance of ≡ C─H peaks along with C–H, C=C and C ≡N bond destabilization following degradation. Energy-dispersive X-ray (EDX) analyzers of the native and decomposed e-polymer samples revealed a considerable loss in elemental weight % of oxygen by 8.4% and silica by 0.5%. Magnesium, aluminium and chlorine which were previously present in the untreated sample, were also removed after treatment by the bacterial action. When seeds of Vigna radiata were screened using treated soil in the presence of both e-waste and the chosen potent bacterial strain, it was also discovered that there was reduced toxicity in terms of improved germination and growth metrics as a phytotoxicity criterion.

P16.07.B PROSPECTIVE DOUBLE ARM PHASE 2 RANDOMIZED TRIAL FOR PATIENTS WITH MULTIPLE BRAIN METASTASIS AND/OR LEPTOMENINGEAL CARCINOMATOSIS: COMPARISON OF WHOLE BRAIN RADIATION THERAPY (WBRT) ALONE AND WBRT PLUS SILIBININ

Abstract BACKGROUND Occurrence of brain metastases (BMs) is increasing given availability of Magnetic Resonance Imaging (MRI) able to detect also small brain lesions, and most effective systemic therapy able to better control extra-cranial disease. Estimated 20% of patients with cancer will develop BMs. In case of limited brain metastases, radiosurgery or hypofractionated radiosurgery is treatment of choice. A subgroup of patients characterized by extensive brain disease and/or leptomeningeal carcinomatosis can require whole brain radiotherapy (WBRT). Since the 1950s, WBRT has been the most treatment used for patients with multiple BMs, given its effectiveness in palliation, widespread availability, and ease to deliver. However, the median overall survival (OS) recorded is restricted to 3 months, on the average. A better understanding of molecular and cellular mechanisms underlying brain metastasis might be expected to lead of improvements in overall survival. Recent studies demonstrated that active signal transducer and activator of transcription 3 (STAT3) in reactive astrocytes correlates with reduced survival from diagnosis of intracranial metastases. Blocking STAT3 signaling in reactive astrocytes reduces experimental brain metastasis, even at advanced stages of colonization. Silibinin is a natural polyphenolic flavonoid isolated from seed extracts of herb milk thistle. It has been shown to impair STAT3 activation, and in preclinical studies, show an anticancer effects in vitro and in vivo. Based on this background, we designed a double arm phase 2 randomized trial evaluating the benefit of Silibinin associated to WBRT respect to WBRT alone. Primary endpoint is OS, secondary endpoints are toxicity in term of corticosteroid therapy use, brain failure (BF) and progression free survival (PFS). MATERIAL AND METHODS Forty-four patients will be enrolled in two years. Patients with histological or cytological confirmation of solid tumor malignancy, clinical indication for WBRT and Karnofsky performance status (KPS) ≥60 will be enrolled. In arm A experimental, WBRT is concomitant to Silibinin, in arm B control, WBRT alone will be administered. In both arms, total dose of radiotherapy is 30 Gy in 10 fractions. Quality of life and use of corticosteroids will be evaluated first, last day of RT, and during follow-up. Outcome will be evaluated by MRI or CT at 2 months after RT, and every 3 months thereafter. RESULTS From March 2023, 6 patients were enrolled, 2 patients in Arm A and 4 in arm B. Primary histology was breast cancer in 3 patients and non small cell lung cancer in 3. In arm A, 1 patients dismissed RT for worsening of general conditions related to rapid lung progression. CONCLUSION WBRT with or without Silibinin was well tolerated, no acute toxicities or increase of corticosteroids were observed.

The acute vapour inhalation toxicity of 2-butoxyethanol. Points considered when designing and conducting a study in Guinea pigs and evaluating existing inhalation toxicity data on low volatility solvents

This publication reports the outcome of an acute inhalation toxicity study with guinea pigs by nose-only exposure to the substance 2-butoxyethanol at exposures close to the maximum attainable saturation vapour concentration. We describe the methods used to ensure exposure only to saturation vapour at a level as high as could be practically achieved whilst avoiding aerosol formation. We consider the practical difficulties and implications of testing substances at or close to their saturation vapour concentration and the criteria that should be used to critically assess such studies, especially with reference to the GHS (Globally Harmonised System) for classification and labelling, where a clear differentiation between gases, vapours and dust and mists applies. Guinea pigs showed no adverse effects when exposed for 4 h to the maximum attainable concentration of pure 2-butoxyethanol vapour. If guinea pigs are regarded as the most appropriate species to assess short term toxicity to humans from exposure to 2-butoxyethanol, because they are like humans not sensitive to haemolysis of red blood cells caused by exposure to the substance, then the data from this study shows that 2-butoxyethanol presents a low acute inhalation toxicity hazard.

Realgar toxicity in terms of its chemical characterization, pharmacological mechanisms, and metabolic profile: A review

Abstract Realgar is an arsenic-containing Chinese medicine known for its toxin-removing, phlegm-dispelling, and malaria-intercepting effects. It has proven to be effective in the treatment of acute promyelocytic leukemia. However, because of the harmful nature of arsenic to human health, realgar is considered a “poison” in many countries, raising concerns about the toxicity and safety of realgar and its preparations. The Shuifei process (grinding with water) of realgar plays a crucial role in ensuring its safety as a Chinese medicine. The major ingredient of realgar, As4S4, is water insoluble and poorly absorbed by the human body. Therefore, it is important to note that the toxicity and health risks of realgar to humans are overestimated by solely considering the amount of arsenic. Realgar processing is an indispensable method to ensure the quality of medicinal realgar, involving purification, powdering, detoxification, and synergism. This article not only highlights possible mechanisms through which realgar exerts pharmacological effects but also reviews the literature regarding its toxic features and potential mechanisms. Currently, realgar toxicity research primarily relies on animal experiments, and clinical data on its adverse reactions are relatively limited. The toxicity of arsenic is closely related to the form and valence of its major metabolites in the body. Animal studies have confirmed that, when realgar enters the body, the major form of arsenic metabolized is dimethylarsenic acid; therefore, it was considered that the toxicity of realgar induced by high doses might be associated with the accumulation of dimethylarsenic acid produced in the methylation pathway of inorganic arsenic. Realgar is generally less toxic when used in safe doses, but prolonged use may pose a significant risk. It is rarely used alone and is often combined with other Chinese medicines in an attempt to reduce toxicity. Scientifically and reasonably limiting the arsenic content of realgar-containing Chinese patent medicines is an effective way to improve the safety of realgar in clinical medication.

Risk of Macular Toxicity After Intra-Cameral 1mg/0.1 ml Cefuroxime for Endophthalmitis Prophylaxis in Phacoemulsification Cataract Surgery

The world's leading culprit of preventable blindness is cataracts. For numerous decades, postoperative endophthalmitis has instilled terror as a potential complication of cataract surgery. Objective: To determine the frequency of retinal toxicity in terms of transient macular edema following using per-operative intracameral cefuroxime 1mg/0.1ml for endophthalmitis prophylaxis. Methods: A Descriptive case series was done at LRBT Eye Hospital, Lahore, from 15th Dec 2020 to 14th Jun 2021. A total number of 118 senile cataract patients were included. After cataract surgery, an intracameral 1 mg injection of cefuroxime was given to each patient. The optimally corrected visual acuity and macular thickness at the center of the retina on OCT were assessed postoperatively at week 1. If they were found to be elevated, it was labeled as retinal toxicity. Data were collected on data collection proforma. Results: The average age of the participants was 59.68 ± 5.28 years. Mean visual acuity before and after surgery was 2.01 ± 0.74 and 1.92 ± 0.94, respectively. Mean central macular thickness before and after surgery was 241.08 ± 4.73 and 248.74 ± 5.86 µm, respectively. There were 71 (60.17%) male and 47 (39.83%) female patients. There were 42 (35.59%) farmers, 40 (33.90%) job holders, 05 (4.24%) business people, and 31 (26.27%) non-working patients. Retinal toxicity was found in 54 (45.76%) patients. Conclusions: Intracameral injection of cefuroxime sodium can result in transient macular edema and retinal toxicity. In this study, retinal toxicity occurred in 45.8% of patients undergoing phacoemulsification.

Are PFBS, PFHxS, and 6:2FTSA more friendly to the soil environment compared to PFOS? A new insight based on ecotoxicity study in soil invertebrates (Eisenia fetida)

As alternatives to perfluorooctane sulfonate (PFOS) with shorter carbon chains or lower proportion of fluorine atoms, perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and 6:2 fluorotelomer sulfonic acid (6:2FTSA) have been detected in various environmental media. However, it is unclear whether the toxicity of these alternatives is lower than that of PFOS. Therefore, this study investigated the toxicity and differences in PFBS, PFHxS, 6:2FTSA, and PFOS (0.2 mg/kg) after 56 d of exposure using the common invertebrate Eisenia fetida in soil as the test organism. The results showed that although PFOS, PFBS, PFHxS, and 6:2FTSA induced oxidative stress and apoptosis in earthworms and led to developmental and reproductive toxicity in terms of comprehensive toxicity, PFHxS > PFOS > PFBS >6:2FTSA. To reveal the mechanisms underlying the differences in toxicity between the alternatives and PFOS, we conducted molecular docking and transcriptomic analyses. The results indicated that, unlike PFOS, PFBS, and PFHxS, 6:2FTSA did not cause significant changes in antioxidant enzyme activity at the molecular level. Furthermore, PFOS exposure caused disorder in the nervous and metabolic systems of earthworms, and PFHxS disrupted energy balance and triggered inflammatory responses, which may be important reasons for the higher toxicity of these compounds. In contrast, exposure to 6:2FTSA did not result in adverse transcriptomic effects, suggesting that 6:2FTSA exerted the least molecular-scale toxicity in earthworms. The results of this study provide new insights into the environmental safety of using PFBS, PFHxS, and 6:2FTSA as alternatives to PFOS.

EFFECTS OF CHEMICAL PESTICIDES ON HUMAN HEALTH

The industrialization of agriculture has made natural ecosystems more chemically burdened. Agrochemicals known as pesticides. Use of pesticides is common in controlling weeds and insect infestation in agricultural fields as well as a variety of pests and disease carriers such as mosquitoes, ticks, rodents, and mice in homes, workplaces, shopping centers, and public areas their exposure through numerous pathways such as residues in food and drinking water, inhalation, ingestion, eye, and dermal contact. Although these risks can have short-term effects e.g., skin and eye irritation, headaches, dizziness, and nausea, or long-term effects e.g., cancer, asthma, infertility, allergy, Parkinson’s disease, and birth defects on human health. It is challenging to determine the risks because of the interaction of many variables, including the duration and intensity of exposure, the type of pesticide (in terms of toxicity and persistence), and the environmental characteristics of the affected areas.

Toxicological Study of n-hexane and Chloroform Extracts of Lantana camara L. in Experimental Animals

Abstract: Aim: The aim of the current study is to investigate the acute, sub-acute and sub-chronic toxicity study of extracts (n-hexane and chloroform) of L. camara in Wistar rats. Materials and Methods: HPTLC and GC-MS analysis were carried out to analyze different constituents present in L. camara extract. Acute toxicity study was conducted as per OECD 420 guidelines, while sub-acute and sub-chronic studies were conducted according to OECD 407 and 408 guidelines respectively. Toxicopathological effects of both extracts were tested with the help of hemotoxylin and eosin staining of vital organs (liver, kidney, brain, testes, and ovaries) in experimental animals. Antioxidant and behavioral tests were also conducted on both the extracts, so as to evaluate the possible effects of toxicity. Results: The toxicity investigation of chloroform and n-hexane extracts exhibits no toxicity in terms of hematological (p<0.01) and biochemical parameters (p<0.05). Histopathological sections also confirmed the non-toxic effects on the liver, brain, kidney and on reproductive organs. Conclusion: The n-hexane and chloroform extracts of L. camara can be safely used for therapeutic purposes. Keywords: Lantana camara, GC-MS, HPTLC, Toxicity, Histopathology, Antioxidant, PI uptake.

A safety profile of Siddha formulation Karisalai Chooranam in Wistar albino rats

Introduction and Aim: Karisalai Chooranam (KSC) is used in the traditional Siddha system of medicine for a long time to treat various ailments in the body. Its antistress and antioxidant properties were reported earlier. Investigating the acute and long-term toxicity of Karisalai Chooranam in Wistar albino rats was the goal of the current study. Materials and Methods: For the acute toxicity investigation, Wistar rats were divided into four groups. For fourteen days, the animals were monitored for behavioural changes and toxicological complaints. For ninety days, a total of four categories of animal groups like control, forty mg/kg body weight, two hundred mg/kg body weight and thousand mg/kg body weight were utilized in a long - term toxicity study. The samples of blood were taken on the final day of the trial for biochemical and haematological examination. Animals were sacrificed for monitoring gross necropsy changes and histopathological examination of the liver, kidney and brain. Results: There was no morbidity or death observed in the acute toxicity trial. In the research of long - term toxicity. KSC's haematological and biochemical parameters during analysis did not exhibit any appreciable changes. All the three doses of KSC, the renal and brain histology displayed normal architecture. When the medicine was given to the forty milligram and two hundred milligram dosage groups of animals for 90 days, no toxicity symptoms were present in the case of organ liver. After the medicine was given for 90 days to the thousand milligram dosage group, toxic signs such as programmed and localized cell death became apparent. Conclusion: Toxicity studies proved the safety of KSC in animal models. If KSC is utilized clinically as prescribed in literature, it will not cause any adverse effects.

The Enemy Hates Best? Toxicity in League of Legends and Its Content Moderation Implications

In recent decades, many sectors of our society have been digitized, and much of our life has moved to cyberspace, especially in terms of entertainment. Users meet, relate, and cooperate in the new public space that is the internet and form digital communities. Video games play a leading role in the formation of such communities. However, these communities also present antisocial behaviors, ranging from disruptive actions to harassment and hate speech. Such behaviors, encompassed under the umbrella term toxicity, are a major concern for both users and those in charge of moderating these spaces. This article focuses on toxicity in today’s leading online video game League of Legends. Three hundred twenty-eight matches were reviewed using a system of two judges to study the prevalence of these problematic behaviors. We find that 70% of matches were affected by disruptive behavior. Nevertheless, only 10.9% of the analyzed matches were exclusively affected by downright harmful behavior. In our view, the results have relevant implications for content moderation policy that are also addressed in this paper.

A Brain, A Heart, and the Courage: Balancing Benefit and Toxicity of Immunotherapy in Melanoma

The overall survival of advanced melanoma has improved dramatically. Immunotherapies, specifically checkpoint inhibitors, have played a large role in this improvement. These agents have also shown benefit in the adjuvant setting, are approved for treatment of resected stage II, III, and IV melanoma, and play an evolving role in the neoadjuvant setting. Although generally well tolerated, immune-related adverse events occur and can be severe. Here we focus on some severe and potentially long term toxicities, including cardiovascular and neurologic toxicities. Our understanding of the acute and long-term toxicities of immune checkpoint inhibitors continues to evolve. Oncologists must continue to balance cancer risk and treatment-related toxicities.

Eutrophic reservoir water suitability for irrigation in semi-arid region

Eutrophication is a common problem for the dams situated within an urban or agricultural catchment with a high source of untreated plant nutrients. This can negatively affect the hydro ecosystem, recreational and other uses of water. On the other hand, such eutrophic dams could also be a rich source of nutrients for agricultural use. Thinking irrigation as an alternative means of eutrophic reservoir water management, water suitability for irrigation was investigated for Roodeplaat Dam, South Africa using physicochemical parameters recorded (1981–2017) at five sampling stations. Irrigation suitability was evaluated in terms of nutrient content, salinity, soil infiltration, and toxicity problems to irrigated plants. Plant nutrients: NH4_N, NO3_NO2_N, PO4_P, are within the normal range. But K is above the normal range for irrigation use and can cause nitrogen deficiency. The salinity of 0.44 dS/m was found within the normal range with none restriction for irrigation use. Na toxicity in terms of SAR and Cl toxicity was none for both surface and sprinkler irrigated plants. The pH value of 8.4 was within the normal range (6.5–8.4). Generally, the quality of the reservoir water was categorized under C2S1 (medium salinity and low sodium hazard). Irrigation water can cause slight to moderate soil infiltration problem. Therefore, eutrophic reservoirs can be a potential source of readily available nutrients for irrigation and, hence irrigation use can be considered as one of the remedial measures to decrease nutrient accumulation in the reservoir. The existing water conveyance system can be used to transport water to agricultural fields.

Effects of Chromium, Cadmium and Lead on the Growth and Survival of Rats

Eight groups of more than 50 hooded rats were each given (at 5 ppm) cadmium, trivalent chromium or lead in drinking water while fed a diet of rye flour, dried skim milk and corn oil containing no detectable cadmium and only small amounts of chromium and lead. Extensive precautions were taken to avoid environmental metallic contamination. The diet was nutritionally adequate for survival, all but 7 control animals surviving 21 months. Mortality of rats receiving chromium was equally low. Although those given lead and cadmium grew normally, survival was considerably reduced when their tissue concentrations of metal were approximately similar to or less than those of adult human beings. No metallic toxicity appeared. Growth of males was stimulated by chromium and mature animals were larger than the controls. Cadmium was not detected in the livers and kidneys of animals not given it, although they grew normally and survived. Cadmium is not an “essential” trace metal for rats in terms of growth and survival; it shortens their lives at less than human renal concentrations. Lead at human tissue concentrations has a similar innate toxicity in terms of survival. If chromium has a metabolic function, these experiments confine it to male rats.

Abstract P5-08-17: Monitoring for cardiotoxicity in early breast cancer: an Australian experience

Abstract Background Breast cancer is the most commonly diagnosed cancer in Australia. Patient outcomes continue to improve with current 10 year survival of 86%. Given this, greater focus is needed to minimise potential long term toxicities of prescribed therapies. Anthracyclines and HER2 targeted therapies are commonly prescribed agents for high risk early breast cancers and are associated with acute and long term cardiotoxicity. Despite this, screening of cardiotoxicity in Australian patients receiving these therapies remains variable due to a lack of endorsed national screening guidelines. We conducted a retrospective review of screening procedures for cardiotoxicity in 2 major oncology centres in metropolitan Sydney and compared the findings to current international recommendations from ASCO/ESMO guidelines. Methods Patients were included if they received doxorubicin, epirubicin or trastuzumab with neoadjuvant or adjuvant intent during 2021. Baseline patient and tumour characteristics including cardiovascular risk factors were reviewed. Baseline ECG, transthoracic echocardiogram (TTE) or cardiac biomarkers (cardiac troponin or brain natriuretic peptide) were recorded, as well as frequency of serial monitoring and incidence of cardiotoxicity and cardiology referrals. Results 111 patients receiving initial curative therapy were included of which 45 received anthracycline therapy without trastuzumab. 66 received trastuzumab of which 34 also received anthracycline. 38 patients were aged greater than 60 and 31 had 2 or more cardiovascular risk factors. Of the patients receiving anthracycline only, 96% had a baseline TTE. All patients receiving trastuzumab only had a baseline TTE and of the 34 patients who received anthracycline and trastuzumab 3 did not undergo baseline TTE but underwent one prior to commencing trastuzumab. 3 patients total had a baseline ECG. No patients had baseline biomarkers measured. Only 5 patients had biomarkers measured at 1 year and all 5 had developed grade 1 heart failure on treatment. These 5 patients were referred for cardiology review and 2 required an interruption of trastuzumab. All patients receiving trastuzumab underwent 3 monthly TTEs on treatment. Of the 35 patients now more than 1 year post treatment completion, only 3 patients had a TTE at 12 months. No patients referred to cardiology have reached 12 months post treatment. Discussion International guidelines recommend screening to identify and treat early cardiotoxicity and prevent long term morbidity. ASCO and ESMO guidelines both recommend patients receiving anthracycline undertake a TTE at baseline and at 6-12 months after completing therapy. Both recommend 3 monthly TTEs for patients receiving trastuzumab. The ESMO guidelines recommend a baseline ECG and consideration of further TTE at 2 years post therapy. For high risk patients the ASCO guidelines discuss offering routine TTEs during treatment. The ESMO guidelines recommend measurement of cardiac biomarkers for patients receiving anthracycline prior to each cycle and routine monitoring can be considered for patients receiving anti HER2 therapy. The ASCO guidelines reserve use of cardiac biomarkers for patients who develop signs or symptoms of cardiac dysfunction. Our study demonstrates that while baseline cardiac assessment is well performed a personalised approach to cardiac monitoring during curative therapy is not. These were unexpected findings given both treatment units are located in well resourced areas of Sydney. An outcome of this study has been the development of a cardio-oncology group within our oncology and cardiology departments. This has led to the development of new clinical guidelines to screen and manage high risk breast cancer patients receiving cardiotoxic therapies. This has empowered patients, care coordinators and physicians to proactively manage cardiac risks from therapy and we hope these institutional guidelines will be adopted nationally. Citation Format: Brendan Kirwin, Lina Pugliano, Sally Baron Hay. Monitoring for cardiotoxicity in early breast cancer: an Australian experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-17.

Comparative effects of copper nanoparticles and copper oxide nanoparticles on physiological characteristics and mineral element accumulation in Brassica chinensis L

In this study, the short–term toxicity of Cu NPs, CuO NPs, and CuSO4 on bok choy (Brassica chinensis L.) under hydroponic conditions was evaluated using indicators such as biomass, net photosynthesis rate, root morphology, enzyme activity, and Cu accumulation and subcellular distribution. Results showed that CuO NPs exposure notably increased the biomass, root length, and root tip number by 22.0%, 22.7%, and 82.9%, respectively, whereas Cu NPs and CuSO4 significantly reduced root biomass, net photosynthetic rate (PN), and root length by 31.2% and 44.2%, 24.5% and 32.2%, and 43.4% and 40.6%, respectively. In addition, Cu NPs, CuO NPs and CuSO4 exposure increased the distribution of Cu in soluble component and cell wall. Moreover, short–term exposure to different Cu forms significantly affected mineral element accumulation in bok choy. For instance, Cu NPs exposure reduced the concentrations of Mg, Ca and Mn in edible part by 21.7%, 16.1% and 23.2%, respectively. CuSO4 exposure reduced the concentrations of Mg and Ca in edible part by 12.3% and 50.1%, respectively. CuO NPs caused a significant increase of 30.4% for Ca concentration in root, 34.5% and 34.5% for K and Mn concentration in edible part. Over all, CuO NPs exposure was beneficial for plant growth. These findings help understand the phytotoxic effect of different Cu forms on bok choy, and CuO NPs has the potential to be applied to improve nutrition and prompt growth in edible plants.

Abstract P1-10-01: Postmastectomy electron beams radiation therapy (PMERT) : long term results

Abstract Background/Purpose: This study evaluates the toxicity after radiotherapy after mastectomy without reconstruction in patients irradiated to the chest wall using previously reported technique of PMERT. Materials/Methods: We included all women irradiated after mastectomy for not metastatic breast cancer with PMERT between 2007 and 2011 in the Department of Radiation Oncology of the Institut Curie. Previously reported technique using mostly electrons was evaluated in terms of efficacy and toxicity. Acute and late toxicities were assessed retrospectively using CTCAE v.4.0. A clinical exam was weekly performed during radiotherapy and one and three months following the completion of radiotherapy. Patients were then followed as recommended in Institut Curie guidelines (Senorif). Quantitative and qualitative data were described respectively as means and proportions. Statistical comparisons were computed using X² or Fischer’s exact test for categorical data. Recurrence free survival (RFS) was defined as the time between the end of treatment and the date of recurrence or death. Overall survival was the same but recurrences were not taken into account. Patients who did not experienced any event were censored at the date of last news. Results: Among the 796 women included, 51.3% had multifocal lesions, 10.1% a triple negative (TN) status and 18.8% a HER2+ positive status; 196 (24.6%) received a neoadjuvant chemotherapy, and 208 (26.1 %) a systemic therapy during radiotherapy (chemotherapy and/or targeted therapy); 514 (64.6%) had at least one positive lymph node (LN). Internal mammary chain (IMC) was treated in 85.6% of cases, supraclavicular LN (L4) in 88.3% of cases, infraclavicular (L3-2-IP+/- L1) LN in 77.9% of cases and low axilla (L1) in 14.9% of cases. With a median follow up of 113 months [range : 2-164] locoregional recurrence-free survival and overall survival at 10 years were respectively 94.02 (IC95% : 92.13-98.94) and 79.84 (IC95% : 76.83-82.97). The median survival was not reached. In the long term, 29.6% of patients had telangiectasia (grade 1: 23.3%, grade 2: 5.2% Grade 3: 1.1%). Totally 279 patients (35.1%) had breast reconstruction, on average 21 months after the end of radiotherapy. Twenty-five patients (3%) had early esophageal toxicity, not exceeding the grade 1. Of these patients, 21 had had chemotherapy and all were irradiated on the lymph nodes (24 including the IMC). Irradiation of the IMC was not associated with an increased chronic lung toxicity (OR=1.03 [0.98-1.09]). There were 35 patients who developed heart disease after the end of the treatment. Of them, 30 patients had received anthracyclines (p=1.05) and 9 trastuzumab (p =1.09). Four patients developed ischemic heart disease, 3/4 irradiated on the left chest wall, all on the CMI and supra and infraclavicular LN, but all of them presented multiple cardiovascular risk factors (2 to 4). Conclusions: Our series have shown that the PMERT using the Institut Curie technique is effective and well tolerated. Table 1. patients and tumor characteristics (n=796). HR+ : hormonal receptor positive HER2+ : HER-2 overexpressed Cardiovascular risk factor : (smoking, hypertension, dyslipidemia, diabetes, obesity, family history of coronary heart disease or vascular events) as described by the French Health Authority (HAS, Haute Autorité de Santé). Table 2. Efficiency (n=796, median follow-up: 113 months; range : [2-164]). HR+ : hormonal receptor positive HER 2+ : Her-2 overexpressed TNBC : Triple negative or basal-like cancer, OS : overall survival LRFS : local recurrence free survival LRRFS : locoregional recurrence free survival MFS : metastasis free survival Multivariate analysis : long term toxicity IMC irradiation : Irradiation of the internal mammary chain, OR : Odd ratio Citation Format: Souidi Sami, Pierre Loap, Alain Fourquet, Youlia M. Kirova. Postmastectomy electron beams radiation therapy (PMERT) : long term results [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-01.

Developmental toxicity of a pymetrozine photo-metabolite, 3-pyridinecarboxaldehyde, in zebrafish (Danio rerio) embryos: Abnormal cardiac development and occurrence of heart dysfunction via differential expression of heart formation-related genes

Pymetrozine (PYM) is worldwide used to control sucking insect pests in rice-cultivated fields and it is degraded into various metabolites including 3-pyridinecarboxaldehyde (3-PCA). These two pyridine compounds were used to determine their impacts on aquatic environments, particularly on the aquatic animal model zebrafish (Danio rerio). PYM did not show acute toxicities in terms of lethality, hatching rate, and phenotypic changes in zebrafish embryos in the tested ranges up to a concentration of 20 mg/L. 3-PCA exhibited acute toxicity with LC50 and EC50 values of 10.7 and 2.07 mg/L, respectively. 3-PCA treatment caused phenotypic changes including pericardial edema, yolk sac edema, hyperemia, and curved spine, at a concentration of 10 mg/L after 48 h of exposure. Abnormal cardiac development was observed in 3-PCA-treated zebrafish embryos at a concentration of 5 mg/L with reduced heart function. In a molecular analysis, cacna1c, encoding a voltage-dependent calcium channel, was significantly down-regulated in the 3-PCA-treated embryos, indicating synaptic and behavioral defects. Hyperemia and incomplete intersegmental vessels were observed in 3-PCA-treated embryos. Based on these results, it is necessary to generate scientific information on the acute and chronic toxicity of PYM and its metabolites with regular monitoring of their residues in aquatic environments.