Subchronic Oral Toxicity Evaluation of Lanthanum： A 90-day, Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.

Obtaining the Minimum Lethal Dose against <i>Fasciola hepatica in Vitro</i>Using Plant Extract Hexanes with Fasciolicide Activity and Toxicity Evaluation on CD1 Male Mice

Fascioliasis is a parasitic disease of worldwide distribution affecting mainly cattle and sheep. Its importance lies in the economic losses it produces in the livestock industry. Its control is carried out by using a chemical fasciolicide showing resistance problems and environmental contamination. Looking for an alternative control for this disease the present study was aimed at determining the hexane anti-Fasciola hepatica in the in vitro effect of some plant extracts and the minimum lethal dose of the mentioned extracts. All selected plants were tested in vitro at concentrations of 500, 250, 125 and 50 mg/L):Achilleamillefolium (plumajillo), Artemisiaabsinthium (wormwood), Artemisia mexicana (estafiate), Castelatortuousa (chaparroamargo), Chenopodiumgraveolens (epazote de zorrillo), Gymnospermaglutinosum (popote) Justicia spicigera (muicle), Limpia critridora (cedron), Lippiagraveolens (oregano), Menthapiperita (Mint), Populus alba (alamo) and Thymusvulgaris (thyme). Subsequently proceeded to perform a toxicity study with these fractions in CD1 male mice 10-13 weeks of age, forming groups of 3-5 animals they were administered a single oral dose being (5 mg/kg, 50 mg/kg, 500 mg/kg, 2500 mg/kg and 5000 mg/kg) and were kept under observation 20 days, later were sacrificed and a kidney and liver histology was performed, finding the safety of the extracts. To perform the toxicity study with these fractions, groups of five CD1 male-mice were formed, they were treated with oral doses of 5, 50, 500, 2500 and 5000 mg/kg, administered with a cannule. All mice were kept under observation for 20 days. Finally they were sacrificed to perform histology of the kidney and liver in search of possible side effects. Results show that none of the extracts exhibited that fasciolocide activity for mice CD1 even at the highest dose thereforefinding the safety of the extracts.

Image-Guided Radiotherapy Dose Escalation in Intermediate and High Risk Cancer Prostate Patients and Its Effect on Treatment Toxicity

Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.

Acute Toxicity (Lethal Dose 50 Calculation) of Herbal Drug Somina in Rats and Mice

Somina (herbal preparation) prepared by Hamdard Laboratories (Waqf) Pakistan is a mixture of five different medicinal plants, widely prescribed for the treatment of mental illness. For acute toxicity, the Karber arithmetic method for the calculation of LD50 and Hodge and Sterner toxicity scale was used. In this study, different doses (10, 100, 285, 500, 1000, 5000 and 10,000 mg/kg) of the extract was administered orally to the different groups of rats and mice. Signs of toxicity and possible death of animals were monitored for 24 hrs to calculate the median lethal dose (LD50) of somina. At the end of the study, all the animals in all the dose groups were sacrificed and the internal organ-body was compared with values from the control group. The LD50 was found to be >10,000 mg/kg body weight upon oral administration in mice and rats as no mortality was observed after single dose administration. According to Hodge and Sterner toxicity scale, the obtained value of LD 50 > 10,000 mg/kg classified the Somina as Practically non-toxic herbal medicine.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

Acute Toxicity of Three Dimensional Conformal Concurrent Chemoradiation with Dose Optimization for External Beam Radiation in Carcinoma Cervix—A Prospective Study

Aim: To prospectively evaluate the acute toxicity of 3D conformal radiotherapy with dose optimization in patients with carcinoma cervix. Materials and Methods: Carcinoma cervix patients stage IIB to IIIB (n = 30) treated during November 2011 to May 2013 at the institution with 3D conformal chemo-radiation were included in the study. They received weekly Cisplatin 40 mg/m2 for a maximum of 5 cycles. They received 46 Gy/23 fractions, 5 fractions per week of external beam radiation. In these patients dose optimization was done in order to achieve a tumor maximum dose (Dmax) around 105%. Various techniques were used for dose optimization which included the use of sub fields, adjusting the weightages, using wedges and the use of mixed energies. EBRT (External Beam Radiotherapy) was followed by two fractions of high dose rate intracavitary brachytherapy of 9 Gy each. Acute RTOG toxicity was assessed weekly during EBRT and 1 week post EBRT. Results: The median age of the patients was 45 (range: 30 - 55 years). All the patients completed EBRT;63.3% of the patients received all 5 cycles of chemotherapy while 26.6% of the patients received 4 cycles of chemotherapy and 10% of the patients received 3 cycles of chemotherapy. The most predominant toxicity seen was GI toxicity, diarrhea being the most common GI toxicity followed by vomiting. Neutropenia was the most common hematological toxicity. Most patients had grade 0 and grade 1 toxicity. None of the patients had grade 4 toxicity while few had grade 2 and 3 toxicity. Conclusion: 3D conformal concurrent chemo radiotherapy with Dmaxaround 105% reduces acute RTOG toxicity particularly grade 3 and 4 and improves patient compliance for concurrent chemo-radiotherapy.

Acute Oral Toxicity Test of Radix aconiti lateralis preparata in Kunmin Mice

[Objective] This study aimed to investigate the acute oral toxicity of crude monkshood （Radix aconiti lateralis preparata）. [Method] Monkshood alcohol extract was prepared using soxhlet extractor. The maximum drug dose, which was the minimum dose causing 100% lethally rate in the preliminary test, was diluted into seven con- centrations in formal test. Then every mouse was orally administrated with 0.04 ml/g of the monkshood solution at single time for 7 d. Median lethal dose （LD50） and 95% confidence limit were calculated by the improved Karber method formulas. [Result] LD50 of monkshood ethanol extract was 230.12 mg/kg and 95% confidence limit of LD50 was 80.39-658.57 mg/kg. [Conclusion] Crude monkshood alcohol extract can quickly induce acute toxicity in mice.

Acute Toxicity Test of Chinese Herbal Compound Tongmai Tangyanming Capsule

[Objective] This study was conducted to determine the safe dose of Tongmai Tangyanming capsule in clinic by evaluating its acute toxicity, so as to ensure clinical medication safety. [Method] The test was designed according to ＂Technique Requirements of Research of New Chinese Medicine＂ and ＂Guide for Research of New Chinese Medicine＂, mice were intragastrically administrated with Tongmai Tangyanming capsule at a maximum concentration and a maximum volume, and the acute toxic response of mice was observed, so as to determine medi- na lethal dose （LDso） and maximum administration dosage of Tongmai Tangyanming capsule. [Result] The LD^o could not be detected in the test, and the maximum administration dosage of mouse was calculated to be 112.104 g of dried herbs/（kg.d）, equivalent to 260 times of clinical dose of adult. [Conclusion] Chinese herbal compound Tongmai Tangyanming capsule has low acute toxicity, and its clinical dose is safe and reliable.

Acute Toxicity of Oxytropis Kansuensis Bunge on Rats

[ Objective] The paper was to study the acute toxicity of Oxytropis Kansuensis Bunge on rats. [ Method ] Forty rats were randomly divided into two gToups： control group （distilled water） and trial group （water extract of 0. Kansuens/s） to carry out the acute toxicity experiment. The trial group was supplied with the maximum dose （6.0 g/ml,0.8 ml/20 g） twice per day for continuous 7 d. [Result] The maximal tolerance dose of rats to water extract of O. Kansuens/s was more than 480 g/kg. Feeding rats with O. Kansuens/s would not lead to the death of rats within short time （7 d） and no obvious macroscopic pathological changes in the viscera of rats could be seen in naked eyes. [Condusion] The study provided theoretical basis for full use of O. Kansuens/s resources.

Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose

The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.

Toxicity effects of water extracts of Holothuria atra Jaeger in mice

Objective:To determine lethal median dose(LD_(50)) and histopalhological toxicity of water extract of Hololhuria atra(H,atra) in mice.Methods:The behavioral changes,mortality and histopathology examination on liver were assessed in mice 14 d after the administration(i.p.) of H.atra water extract.Seven doses 110,20,30,50.100.150 and 200 mg/kg) of H.atra were used.The control group was treated with normal saline,Results:In the acute study in mice,the water extracts of H,atra caused dose-dependent general behavior adverse affects and mortality.The main behavioral sign of toxicity was hypoactivity,noticed immediately after administration of the extract which was more obvious at the higher doses and persisted until death.Mortality increased with increasing doses,the calculated LD_(50)was 41 mg/kg in mice.The liver toxicity was confirmed by histopalhological examination,which indicated the presence of abnormal hepatocytes with a distorted shape and undefined cell lining as well as enlarged nuclei in low doses groups.High doses groups indicated a more prominent distortion of the polyhedral hepatocytes with undefined cell lining,massive cytoplasm,pvknotic.karyorhexis and karyolytie nuclei(necrosis of hepatocytes).Control group showed polyhedral hepatocytes with defined cell lining arranged in cords and normal round nuclei,with granular cytoplasm.Conclusions:Because of the relatively low LD_(50) value in the acute study in mice,it may be concluded that the H.atra water extract is toxic.

Acute Oral Toxicity Studies of a Chinese Herbal Preparation Shenrong Bunao Capsule

[ Objectives] This study was conducted to evaluate the acute oral toxicity of Shenrong Bunao Capsule, and to provide a theoretical basis for drug devel- opmcn! and clinical trims. [ Methods] Kunming mice were randomly assigned into two groups： an experimental group and a control group. In experimental group, Shenrong Bunao Capsule solution at maximum concentration of 45% was administered orally by gavage once at a dose of 30 ml/kg body weight （ BW）, while an equal volume of saline solution was given in the control group. Then, the appearance, behavior, mental state, diet, feces, urine, coat, skin color, respiration, nose, eyes and oral secretions and other daily activities of the mice were observed for 14 d after drug administration. At the end of the experiment, the mice were dissected, and their main organs were examined histopathologically. [Results] The appearance, behavior, respiration, body posture, response to stimuli and weight gain of the mice in control group were all normal. All the mice given 13. 500 g/kg BW Shenrong Bunao Capsule were alive 14 d after drug administration, and their appearance, behavior, respiration, body posture, response to stimuli and weight gains did not show any abnormality. In addition, the body weights of male and female mice had no obvious difference between the experimental group and the control group at the binging, 7 and 14 d after drug administration （P 〈0.05）. [ Conclusions] A maximum dose 13. 500 g/kg BW Shenrong Bunao Capsule, which was equivalent to 141 times of the recommended dosage for adult men was given to the mice, and did not result in any apparent toxic effects, suggesting that the Chines herbal preparation Shenrong Bunao Capsule has very little acute toxicity, and the commonly recommended dosage in clinical trials is safe.

Acute Toxicity of Oxyclozanide Suspension in Mice by Oral Administration

The safety of oxyclozanidc suspension was preliminarily evaluated through acute toxicity test in mice. Administration dose, formal trial grouping and group interval were determined in pre-trial using incremental method. Formal test was performed using simplified karber＇s method. Changes in sign of mice after ad- ministration were observed; the mortality rate was statistically calculated, and the time of death was recorded; the median lethal dose （LD50） and 95% confidence limit of oxyclozanide suspension were calculated. The results showed the LD50 of oxyclozanide suspension in mice by oral administration was 1. 679 g/kg, and the 95% confidence interval was 1. 439 - 1. 947 g/kg. According to toxicity grading of chemicals, oxyclozanide suspension was low toxic substance.

Phytochemical and Toxicity Study of the Root of Boscia senegalensis Plant: With Indepth Testicular Histopathological Screening

Beyond the efficacy of herbal remedies, there is always a serious concern for safety. A safety study was carried out on the root of Boscia senegalensis (per) plant prior to its intended use in a bioassay. The root of Boscia senegalensis per (capparaceae) was collected from Tureta Local Government Area of Sokoto State in August, 2011 and pulverized into a dry powder. About 700 g of the powder was extracted with methanol for six hours using Soxhlet extractor. The phytochemical study of the plant material was conducted and the median lethal dose (LD50) of the extract was determined in rats orally according to modified Lorkes’ method. A sub-acute toxicity study was carried out with male albino rats dosed 250, 500 and 750 mg/kg body weights daily for 28 days of the extract. The animals were sacrificed on the 29th day and blood collected through cardiac puncture for hematological and biochemical screening for renal and hepatic status. The testes, liver and kidney were collected and stored in 10 percent formalin for histopathological examination. The phytochemicals present in the root alcoholic extract of Boscia senegalensis were alkaloids, phytosteroids and triterpenoids in appreciable quantity, saponins anthraquinones and tannins in moderate quantity while flavonoids were absent. The LD50 is equal to or above 5000 mg/kg body weight. Supportive of the safety profile of the plant, a 28-day oral administration of the extract produced no significant effect on the creatinine, albumin, total protein concentration at all doses and there was a significant reduction in liver enzymes. The hematological evaluation showed that the extract on a prolonged administration had no significant effect. The histology of the kidney and liver were normal. There was a significant increase in the relative weight of the testis, area of the interstitial space and the diameter of the seminiferous tubules when compared to the control group histologically. The plant root extract may be relatively safe (6000 mg/kg body weight) following oral administration in white albino rats and possesses testicular histopathological effect probably due to the presence of alkaloids saponins, triterpenoids and anthraquinones.

Fixed Dose Rate versus Standard Dose Rate Infusion of Gemcitabine and Cisplatin in Advanced Stage Non-Small Cell Lung Cancer

Background: Comparing the efficacy and safety of gemcitabine at a fixed-dose rate (FDR) infusion (10 mg/m2/min) with the standard dose rate infusion in patients with locally advanced and metastatic non-small squamous cell carcinoma (NSCLC). Methods: The study randomized 60 patients with confirmed diagnosis of NSCLC to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 given as a 30-min infusion (Arm A) or at a rate of 10 mg/m2/min (Arm B). Cisplatin 75 mg/m2 was administered intravenously on day 2 in both arms. Results: No difference in overall response rate (46.6% versus 43.3%). Median time to progression for Arm A was 7 months (95% CI, 6.207 - 7.793 months), versus 6 months for Arm B (95% CI, 4.990 - 7.010 months). Median survival time was comparable [12 months (95% CI, 8.588 - 15.412 months) versus 11 months (95% CI, 9.066 - 12.934 months)] respectively. Two-year survival (18% versus 11%, p = 0.38) was detected. No treatment related deaths occurred. Main hematological toxicities were grade I and II neutropenia, in 36.7% and 53.3% respectively (p = 0.044). Grade III anemia was observed in 10% and 6.7% in both arms respectively (p = 0.024). Grade I and II nausea and vomiting was observed in 50% and 46.7%. Conclusions: FDR gemcitabine in combination with cisplatin had equivalent efficacy and more severe hematologic toxicities compared to the standard 30-min gemcitabine infusion with cisplatin in patients with advanced NSCLC.

The Maximum Tolerance Dose of Shenqi Wuweizi Tablet in Mice

Shenqi Wuweizi tablet is a Chinese medicine preparation mainly composed of Codonopsis pilosula, Astragalus membranaceus, Kadsura longipedunculata and Ziziphus jujube with many curative effects. The maximum tolerance dose of Shenqi Wuweizi tablet in mice was studied, and its acute toxicity in mice was ex- plored. The results showed that Shenqi Wuweizi tablet did not cause the death of mice at the maximum dosage and mice did not show toxic reaction, so it could be used in livestock production and clinical veterinary treatment. The study provided a theoretical basis for application of Shenqi Wuweizi tablet in livestock production and clinical veterinary medication safety.

An assessment of Some Toxic, Essential Elements and Natural Radioactivity, in Most Common Fish Consumed in Jeddah-Saudi Arabia

This study has been carried out to determine the concentrations mg/Kg of the toxic elements (Al, Hg, Cd, Pb, U, Th, and As) and essential elements (K, Sn, Ca, Ni, Cu, Fe, Co, and Mn) using inductively coupled plasma optical emission spectrometer, and the radionuclides concentration levels of (238U, 226Ra, 232Th, 40K and 137Cs) using a high purity germanium spectrophotometer in ten of the most common fish samples collected from local store in Jeddah city, Saudi Arabia during 2014. The results showed that, the concentrations of the elements (Al, Hg, Pb and Cu) in all fish samples were not detected or below the detection limit. The concentrations of metals (Cd, U, Th, As, K, Sn, Ca, Ni, Fe, Co, and Mn) were below the recommended limit by the international organizations. The estimated metal dose (EDI) values for daily average consumption were lower than the recommended values by FAO/WHO, and hazard indices (HI) in fish samples were below safety levels for human consumption (HI 1), then this increase is to be of concern for fish consumer. The measured concentrations in (Bq/Kg) dry weight of natural radionuclides 238U, 226Ra, 232Th, 40K and fallout 137Cs in fish samples were calculated. The results show that the activities in fish samples were of no risk to public health. The total average annual effective dose μSv/y due to intake of 238U, 226Ra, 232Th and 40K from the ingestion of the fish samples were estimated to be 6.07 for infants (≤5 Y), 22.88 and 45.03 for children (5 - 10 Y and 10 - 15 Y) and 56.26 for adults (≥17 y), which are lower than the allowed value (1 mSv). The contribution of 137Cs is nearly negligible. This study could be useful as a baseline data for toxic, essential metals, and radiation, exposure.

Cardiac Safety with High Cumulative Dose of Pegylated Liposomal Doxorubicin in Patients with Metastatic Breast Cancer Previously Treated with Conventional Anthracyclines

Introduction: The treatment of metastatic breast cancer (MBC) is still challenging. Many studies documented the efficacy of pegylated liposomal doxorubicin (PLD) in patients with MBC, but there is a limited data about the cardiac safety with high cumulative dose (HCD) of PLD. Aim of the work: We conducted this trial to outline the cardiac safety of HCD of PLD in patients with MBC who previously received conventional anthracyclines. Methods: During the period of nine years (January 2011 to December 2019). We extracted the data of the patients with MBC receiving PLD at Medical Oncology Department, South Egypt Cancer Institute, Assiut University. These included patients’ demographics and therapeutic data including the full data of PLD, prior conventional anthracyclines, prior trastuzumab, and prior radiotherapy. Also, data about comorbidities as well as cardiac and other toxicities of PLD were obtained. The data was analysed using SPSS v. 21. Results: For all 81 eligible patients, the mean age was 43.9 years (±standard deviation (SD) 13.2). The mean cumulative dose of PLD was 378.4 mg/m2 (± SD of 250.2) and a range of 100 - 1200 mg/m2. About thirty-one (38.3%) patients received high cumulative dose (400 mg/m2 or more), while the remaining 50 patients did not. The decline in left ventricular ejection fraction (LVEF) was relatively rare;and of low grade. Grade 2 decline in LVEF occurred in only two patients who received high cumulative dose of PLD, and only one patient who did not reach HCD (p = 0.555). Grade 3 or 4 decline in LVEF did not occur in patients either with or without HCD. Regarding other toxicities, there was a significant increase in incidence of all grades palmar plantar erythrodysesthesia (PPE) in patients who received HCD of PLD when compared to those who did not reach the HCD (38.7% versus 16% respectively;p = 0.021). Conclusion: Our study concluded that the use of PLD seems to be a justified agent in the treatment of MBC who previously treated by conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.

冬虫夏草及其近缘品中铅、镉、砷污染评价及人体健康累积风险评估方法探索

目的:对冬虫夏草及其近缘品中铅(Pb)、镉(Cd)、砷(As)的残留量进行测定,探索符合冬虫夏草及相关产品使用特点的污染评价及人体健康风险评估方法。方法:基于冬虫夏草及其近缘品中Pb、Cd、As的残留量监测数据,综合运用单因子污染指数法、尼梅罗综合指数法、金属污染指数法对冬虫夏草及其近缘品进行重金属污染评价,计算重金属日暴露量,分别采用危害指数法和更加精确的靶器官毒性剂量法对Pb、Cd、As联合暴露产生的健康风险进行累积风险评估。结果:污染评价结果说明,冬虫夏草及其近缘品中As的污染应引起关注,不同品种污染程度为冬虫夏草(繁育品)=蛹虫草<冬虫夏草(野生品)<香棒虫草<亚香棒虫草;人体健康风险评估结果表明,对于心血管和神经系统,1批冬虫夏草(野生品)全草中Pb、Cd、As联合暴露产生的累积健康风险需被进一步关注。结论:冬虫夏草及其近缘品重金属污染评价,以及人体健康风险评估方法,可为中药安全性评价及相关限量标准的制修订提供参考。