• Title/Summary/Keyword: ACUTE TOXICITY

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Hypofractionated Radiotherapy for Breast Cancers - Preliminary Results from a Tertiary Care Center in Eastern India

  • Nandi, Moujhuri;Mahata, Anurupa;Mallick, Indranil;Achari, Rimpa;Chatterjee, Sanjoy
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2505-2510
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    • 2014
  • Background: The standard radiotherapy (RT) fractionation practiced in India and worldwide is 50Gy in 25 fractions over 5 weeks to the chest wall or whole breast followed by tumour bed boost in case of breast conservation (BCS). A body of validated data exists regarding hypofractionation in breast cancer. We here report initial results for 135 patients treated at our center with the START-B type of fractionation. Materials and Methods: From May 2011 till July 2012, women with all stages of breast cancer (excluding metastatic), who had undergone BCS or mastectomy were planned for 40Gy in 15 fractions over 3weeks to chest wall/whole breast and supraclavicular fossa (where indicated) followed by tumour bed boost in BCS patients. Planning was done using Casebow's technique. The primary end point was to assess the acute toxicity and the cosmetic outcomes. Using cosmetic scales; patients were assessed during radiotherapy and at subsequent follow up visits with the radiation oncologist. Results: Of the 135 patients, 62 had undergone BCS and 73 mastectomy. Median age of the population was 52 years. Some 80% were T1&T2 tumours in BCS whereas most patients in mastectomy group were T3&T4 tumours (60%). 45% were node negative in BCS group whilst it was 23% in the mastectomy group. Average NPI scores were 3.9 and 4.9, respectively. Most frequently reported histopathology report was infiltrating ductal carcinoma (87%), grade III being most common (58%), and 69% were ER positive tumours, and 30% were Her 2 Neu positive. Triple negative tumours accounted for 13% and their mean age was young (43 yrs.) The maximum acute skin toxicity at the end of treatment was Grade 1 in 94% of the mastectomy grouppatients and 71% in BCS patients. Grade 2 toxicity was 6% in mast group and 23% in BCS group. Grade 3 was 6% in BCS group, no grade 3 toxicity in mastectomy patients and there was no grade 4 skin toxicity in any case. Post RT at 1 month; 39% of BCS patients had persisting Grade I skin reaction which was only 2% in mastectomy patients. At 3 months post RT, 18% patients had persisting hyperpigmentation. At 6 months 8% patients had persisting erythema in the BCS group only. Some 3% BCS and 8% mastectomy patients had lymph edema till the date of evaluation. Cosmetic outcome in BCS patients remained good to excellent 6 months post surgery and radiotherapy. 1 patient of BCS and 3 patients of mast had developed metastatic disease at the time of evaluation. Conclusions: Hypofractionated RT is well tolerated in Indian population with reduced acute skin toxicity and good cosmetic outcome. Regimens such as these should be encouraged in other centers to increase machine output time. The study is on-going to assess long term results.

Acute and repeated dose 26-week oral toxicity study of 20(S)-ginsenoside Rg3 in Kunming mice and Sprague-Dawley rats

  • Li, Chunmei;Wang, Zhezhe;Li, Guisheng;Wang, Zhenhua;Yang, Jianrong;Li, Yanshen;Wang, Hongtao;Jin, Haizhu;Qiao, Junhua;Wang, Hongbo;Tian, Jingwei;Lee, Albert W.;Gao, Yonglin
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.222-228
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    • 2020
  • Background: 20(S)-ginsenoside-Rg3 (C42H72O13), a natural triterpenoid saponin, is extracted from red ginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns. Methods: In acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming mice and Sprague-Dawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the 26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26 weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observe the persistence, delayed occurrence, and reversibility of toxic effects. Results: The result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice and rats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-week administration period and a 4-week withdrawal period (recovery period), there were no significant differences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical and hematological values, or histopathological findings. Conclusion: The mean oral lethal dose (LD50) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600 mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, the no-observed-adverse-effect level for female and male SD rats was 180 mg/kg.

Application of Toxicity Identification Evaluation Procedures for Toxic Effluents from the Aluminum Rolling Industry (알루미늄 가공 공장 배출 방류수의 독성 원인물질 탐색)

  • Ra, Jin-Sung;Lee, Jiho;Kim, Ki-Tae
    • Journal of Environmental Health Sciences
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    • v.41 no.5
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    • pp.305-313
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    • 2015
  • Objectives: The objective of this study is to identify toxicants causing acute toxicity in effluents from the aluminum rolling industry that violate the discharge limits in Korea. Methods: Whole effluent toxicity tests (WET) were conducted on effluent discharged from the aluminum rolling industry following the US EPA WET test methods. We collected effluent samples three times and evaluated acute toxicity by using Daphnia magna. We employed toxicity identification evaluation (TIE) procedures to identify toxicants causing toxicity in the effluent. Results: No specific chemical groups were identified in the seven different manipulations applied to the of wastewater effluent samples showing 1.3 toxic units (TU) according to the TIE phase I procedures. Water quality parameters for water hardness, electric conductivity and heavy metals (Mn) were 4,322 mg/l as $CaCO_3$, 11.39 mS/cm, and $5,551{\mu}g/l$, respectively. Considering water hardness and reference toxicity, high concentrations of Mn can be disqualified from the causative toxicants. Consequently, high ionic concentrations of $Na^+$(1,648 mg/l), $Ca^{2+}$(1,048 mg/l), $Mg^{2+}$(1,428 mg/l) and $SO_4{^{2-}}$(7,472 mg/l) were identified to be causative toxicants. Water hardness and electric conductivity exceed the $EC_{50}$ value obtained by biological toxicity tests using Daphnia magna. Conclusion: According to TIE procedures, high salt concentration is determined to be a major toxicant in the effluent of agro-industrial wastewater treatment plants receiving wastewater from the aluminum rolling industry.

Environmental Toxicity of ACQ-Treated Wood Based on the Fish Acute Test (어류급성독성 시험에 의한 ACQ 방부목재의 환경 독성)

  • Woo, Ji-Keun;Kim, Du-Won;Kim, Sung-Kyun
    • Journal of the Korean Society of Environmental Restoration Technology
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    • v.14 no.2
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    • pp.107-115
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    • 2011
  • The purpose of the study is to analyze the environmental characteristics of fish acute toxicity that is dependent on the harmfulness of ACQ (Alkaline Copper Quat)-Treated Wood and Oryzias latipes mortality in a comprehensive way, provide objective verification method on the eco-toxicity and environment-friendliness of landscaping materials and methods, and utilize it as a basic datum for evaluation criteria. The main results are summarized as follows : 1. As a result of analysis on the harmfulness characteristics, each experimental plot showed different values respectively. In particular, it has been found that in proportion to the volume of testing materials, COD and Cu increases at a constant rate, compared to the input water. In the plot C with three testing materials, COD increased 67 times more than that of the input water, and Cu increased up to 12.36mg/L. 2. In case of fish toxicity, plot C, B, A all showed a mortality rate of 100%, indicating that fish toxicity is strong. In particular, the mortality rate of each plot within the initial time of one and a half hour showed clearly, which suggests that the fish toxicity is influenced by the increased concentration of hazardous substances depending on the volume ratio of testing materials. 3. As a result of comparison and analysis on the harmfulness and fish toxicity, the harmfulness showed different values on each experimental plot but, we found that the changing rate of values of toxicity of COD and Cu is mutually similar to that of mortality in the initial hour according to the experiment of fish toxicity, which shows that COD and Cu are major factors to increase fish toxicity.

Acute toxicity response caused by mixture or tank mix of several insecticides (몇 가지 살충제의 혼용 및 혼합 시 독성반응)

  • Lee, Je-Bong;Jeong, Mi-Hye;Sung, Ha-Jung;Lee, Hae-Keun;Yang, Jae-Sul
    • The Korean Journal of Pesticide Science
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    • v.5 no.4
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    • pp.57-61
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    • 2001
  • Tank mixing application of pesticides has been used to reduce labor and to control wide spectrum of pests, but it may cause significant pesticide poisoning on human and animals due to carelessness. The toxic response of pesticides for the tank mixtures and mixtures was investigated to determine acute toxicity and enzymatic change using experimental animals. Acute oral toxicity and acute dermal toxicity were tested by RDA test guideline. The $LD_{50}$ was calculated by probit analysis method and cholinesterase was measured with automatic analyzer. The toxicities were generally higher than estimated toxicities in tank mixing and mixture. Serum cholinesterase activity was inhibited more than expected at the dose levels of 1/5, 1/10 and 1/20 of $LD_{50}$. Therefore, the results of this study showed that acute toxicity caused by the pesticide mixtures should be considered before the tank mixing method is applied.

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Simultaneous determination and acute toxicity study of Fructus mume extracts in ICR mice (오매(烏梅)의 다성분동시분석 및 마우스를 이용한 경구 단회투여 급성독성시험)

  • Lee, In-Sun;Han, Chang-Hyun;Lee, Chul;Hwang, Bang-Yeon;Jung, Sang-Hyeok;Lee, Young-Joon;Jeon, Won-Kyung
    • Journal of Society of Preventive Korean Medicine
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    • v.15 no.1
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    • pp.37-47
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    • 2011
  • Objectives : Previous studies have shown that Fructus mume (FM) has anti-platelet effects. The present study was performed to determine the acute oral toxicity and quality control of a crude extract of FM in ICR mice. Methods : We investigated the in vivo single dose acute toxicity of FM 95% ethanol extract. This test was orally administered once by gavage to 20 male and 20 female mice at dose levels of 0 (control group), 1250, 2500 and 5000mg/kg body weight, respectively. Mortalities, clinical findings, autopsy findings and body weight changes were monitored daily for the 14 days following the administration. HPLC analysis was performed for the simultaneous determination of ursolic acid and p-hydroxycinnamic acid in FM. Reverse-phase chromatography using a C18 column and photodiode array detection at 211 nm was used for quantification of the two maker components. The mobile phase for gradient elution consists of water and acetonitrile. Results : We observed survival rates, general toxicity, change of body weight, and autopsy. The mice did not die after single oral administration of maximum dose of FM. Autopsy of animal revealed no abnormal gross finding. Therefore, $LD_{50}$ value of FM for ICR mice was more than 5000mg/kg on oral route. The HPLC analysis showed that ursolic acid and p-hydroxycinnamic acid amounts to 9.75- and 0.12% in the extract with the retention times of 47.99- and 15.38 minutes, respectively. Conclusions : These results suggest that no toxic dose level of FM in mice is considered to be more than 5000mg/kg. Consequently, it was concluded that FM have no effect on acute toxicity and side effect in ICR mice. For the quality control of FM extract, simultaneous determination of ursolic acid and p-hydroxycinnamic acid was established.

Acute Oral Toxicity of Extract Derived from Fruiting Body of Phellinus gilvus in Rats

  • Bae, Jae-Sung;Jang, Kwang-Ho;Park, Sung-Guk;Jo, Woo-Sik;Rhee, Man-Hee;Kwon, Oh-Deog;Kim, Young-Hoan;Kim, Eun-Young;Park, Seung-Chun
    • Toxicological Research
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    • v.19 no.3
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    • pp.211-215
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    • 2003
  • This study was carried out to investigate the acute oral toxicity of a crude extract derived from fruiting body of Phellinus gilvus (PGE) using male and female SD rats. Groups consisted of five male and female rats were treated with a single dose of the test substance intragastrically at 0, 500, 1,000, 2,000, and 5,000 mg/kgaj, respectively. Clinical signs, body weight change, and food and water consumption change were observed for 14 days after administration. No mortality or abnormal clinical signs in animals were shown during the observation period at the dose used in this study. Also there was no difference in net body weight gain, water and food consumption or gross pathological findings at terminal sacrifice among the groups of rat treated with different doses of the test substance. The results suggested that acute oral toxicity of PGE in rats is very low at the conditions employed in this study and $LD_{50}$ of PGE was estimated to be over 5,000 mg/$\textrm{m}{\ell}$ in both sexes of rats.

Acute Oral Toxicity of Root of Polygala teunifolia Willd. Extract (원지(Root of Polygala teunifolia Willd.) 추출물의 급성 경구투여 독성 연구)

  • Roh, Hang-Sik;Jeong, Ja-Young;Seok, Ji-Hyun;Ha, Hun-Yong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.4
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    • pp.1-13
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    • 2013
  • Objectives: In this study, it was carried out to evaluate the acute oral toxicity of Root of Polygala teunifolia Willd. in Sprague-Dawley (SD) rats. Methods: Male and female rats were administered orally with Root of Polygala teunifolia Willd. water extract of 1,000 mg/kg (low dosage group), 2,000 mg/kg (middle dosage group) and 4,000 mg/kg (high dosage group). We daily observed number of deaths, clinical signs and gross findings for 7 days. After 7 days, we measured body and organs weight. Also we analyzed hematological changes. Results: No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. But we found out histopathological changes in liver fat tissues of female. In addition, there were no significant changes of gross body and individual organs weight. Conclusions: These results suggest that water soluble extract of Root of Polygala teunifolia Willd. has not acute oral toxicity and oral $LD_{50}$ value was over 4,000 mg/kg in SD rats.

Single Dose Acute Toxicity of Ssanghwa-tang in Crl : CD (SD) Rats (랫드에서 쌍화탕의 급성독성에 관한 연구)

  • Kim, Su-Jeong;Lee, Mee-Young;Shin, In-Sik;Seo, Chang-Seob;Ha, Hye-Kyung;Huh, Jung-Im;Shin, Hyeun-Kyoo
    • The Korea Journal of Herbology
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    • v.26 no.2
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    • pp.39-43
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    • 2011
  • Objectives : This study was conducted to evaluate the acute toxicity and safety of Ssanghwa-tang (Shuanhetang in Chinese, Sou-wa-to in Japanese) in Crl : CD Sprague-Dawley (SD) rat though the current regulatory guideline. Methods : In this study, 10 rats of each sex were randomly assigned to two groups of 5 rats each and were administrated singly by gavage at dose levels of 0 and 2000 mg/kg/day of ssanghwa-tang water extract (SHT). After single administration of SHT, mortalities, clinical signs, body weight changes, gross findings were observed for the 15-day period. Results : Acute toxicity tests revealed that a single oral administration of SHT at dose levels of 2000 mg/kg did not affect clinical signs, body weight, and gross findings, evaluating the safety of SHT. The SHT treatment did not result in any toxicologically significant changes in mortality, clinical signs, body weight changes. Conclusions : These results showed that the single oral administration of SHT did not cause any toxic effect at the dose levels of 2000 mg/kg/day in rats. In conclusion, the median lethal dose (LD50) of SHT was considered to be over 2000 mg/kg/day body for both sexes.

Acute and Genetic Toxicity Study of DK1002, a Drug Candidate for Analgesics (DK1002에 대한 급성독성시험 및 유전독성에 관한 연구)

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Kim, Hyun-Joo;Jung, Sang-Oun;Kim, Myung-Kuk;Park, Hee-Sock;Kim, Yong-Hae
    • Toxicological Research
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    • v.14 no.3
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    • pp.427-433
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    • 1998
  • The acute and genetic toxicity of DK1002 was subjected in this study. DK1002 which is a morphine-like new drug candidate synthesized by Dong-Kook Pharmaceutical Co. Ltd. is now under developing as a analgesics that have better drug efficacy and least addictive property. In acute toxicity study, the 50% lethal doses ($LD_{50}$) of DK1002 were determined as>2000mg/kg (p.o.), 237.0mg/kg(i.p.), 57.5mg/kg(i.v.), and 1266.9mg/kg (s.c.). And also, to study the genotoxicity of DK1002, we performed bacterial reversion assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and in vitro chromosomal aberration assay with Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. In vivo micronucleus assay using mouse bone marrow cells was also performed. From these results, DK1002 was revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, and TA537 both in the absence and presecne of metablic activation system. No clastogenicity of DK1002 was observed in chromosomal aberration assay in vitro as well as in micronucleus assay in vivo.

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