• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.6
• /
• pp.2505-2510
• /
• 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.

• Journal of Pharmacopuncture
• /
• v.18 no.4
• /
• pp.45-50
• /
• 2015

Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.

• Environmental Analysis Health and Toxicology
• /
• v.13 no.3_4
• /
• pp.87-94
• /
• 1998

The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Toxicological Research
• /
• v.27 no.4
• /
• pp.231-240
• /
• 2011

Gryllus bimaculatus (Gb) was orally administered at doses of 0, 0.04, 0.2, 1 and 5 g/kg bw/day for 13 consecutive weeks. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of G. bimaculatus was considered to be higher than 5 g/kg in rats. Throughout the administration period, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology were detected. Minor changes were found in hematological parameters for the 5 g/kg Gb-treated group (triglyceride reduction of 35.8%), but all changes were within normal physiological ranges. Microscopic examination did not identify any treatment-related histopathologic changes in the organs of Gb-treated rats in the high dose group. From these results, one can conclude that the no-observed adverse effect level (NOAEL) of G. bimaculatus is higher than 5 g/kg bw/day in rats.

• The Korea Journal of Herbology
• /
• v.28 no.1
• /
• pp.15-21
• /
• 2013

Objectives : To evaluate the safety of KOB, a polyherbal medicine for allergic rhinitis, we conducted a subchronic toxicology study. Methods : Dried extract of KOB(Lot. No. 11003, yield : 41.1%) was prepared from GLP company (Hanpoong Pharm & Food Co., Ltd). KOB was repeatedly administrated orally of male SD rats at daily dose levels of 500 (G2), 1250 (G3) and 5000 (G4) mg/kg/day for 13 weeks. We recorded the clinical signs of toxicity, body weight, food intake/consumption, optometry, urine analysis, organ weights, hematology, and conducted serum biochemical analysis, necropsy, gross and histological changes in target organs of Sprague-Dawley rats, and clinical chemistry analysis. Results : Neither death nor any toxicological signs were obserbed in KOB at all doses of 500, 1250 and 5000 mg/kg/day during the administration period for thirteen-week. Furthermore, there was no difference in body weight and food-take consumption, optometry, necropsy, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of KOB, during at the observation period for thirteen-week. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from repeated-dose administration of KOB in rats during the observation period. Conclusions : Based on these results, the no observable adverse effect level (NOAEL) of KOB was considered to be 5000 mg/kg/day for male rats under these study conditions.

• Toxicological Research
• /
• v.13 no.4
• /
• pp.435-447
• /
• 1997

l-Muscone is synthesized for use as substitutive material of musk which is the active ingredient of woohwangchungsimwon. The objective of this investigation was to evaluate the acute and subacute toxicity of l-muscone in rats. In oral acute toxicity test, SPF Sprague-Dawley male and female rats were gayaged with l-muscone of two doses(0, 5.0 g/kg). No dead animal and abnormal autopsy findings were found in control and treated group. Body weights were slightly decreased in both sexes of rats treated with 5.0 g/kg. Therefore, oral $LD_{50}$ of l-muscone was consider to be higher than 5.0 g/kg in male and female rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with dosages of 0, 1,000, 1,316, 1,732, 2,279 and 3.000 mg/kg. Decreased body weights and motor activities were observed at high dose group. Intraperitoneal $LD_{50}$ of l-muscone were 1,920 mg/kg in male and female rats. In the subacute study, l-muscone was administrated orally to both sexes of rats for 4 weeks as several doses(0, 10, 100 and 1,000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysist and other findings. Above data suggest that no observed adverse effect level of l-muscone in rats might be over 1,000 mg/kg/day in this study.

• Toxicological Research
• /
• v.13 no.1_2
• /
• pp.103-110
• /
• 1997

This study was performed to investigate the effects of cadmium chloride on the acute and chronic toxicity on rats. Several toxic effects of cadmium has been shown following short-term and longterm pretreatment with cadmium and zinc. Four groups of rats (A, B, C, D), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with $CdCl_2$ (0.5 mg/kg, A & C), and $ZnCl_2$ (13.0 mg/kg, B & D) during time periods of 1 weeks (group A & B) and 6 weeks (group C & D). At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, i.p.). After giving the challenge dose, cadmium and metallothionein(MT) concentrations were determined. The concentrations of cadmium were higher in the liver than the kidney irrelevantly to cadmium and zinc pretreatment and increased dose-dependently to the challenge dosage. The metallothioneins showed higher concentrations in the liver than the kidney following cadmium pretreatment and were higher in the long-term pretreatment groups than the short-term pretreatment groups in the liver and the kidney of rats. These data suggest that metallothioneins are induced preferentially in the liver by pretreatment of cadmium and then, formed in the form of Cd-MT, may play an important role in the nephrotoxicity.

• Korean Journal of Medicinal Crop Science
• /
• v.27 no.3
• /
• pp.173-185
• /
• 2019

Background: Galgeun-tang used in traditional Korean medicine, is a mixture of the medicinal plants Cinnamomi Ramulus, Ephedrae Herba and Puerariae Radix, and has been prescribed for the treatment of various ailments, including fever. Although the use of traditional medicinal herbs to treat diseases has recently increased, their safety and toxicity profiles incompletely elucidated. Thus, we evaluated Galgeun-tang's toxicity in male and female Sprague-Dawley rats. Methods and Results: Galgeun-tang (1,000, 2,000 and 4,000 mg/kg) was orally administered to rats for 13 weeks, and then, they were maintained for 4 weeks without administration (recovery period). Their clinical signs, and hematological and urinary properties, were monitored. The results showed that Galgeun-tang administeration slightly increased serum creatinine, urea nitrogen and, aspartate aminotransferase levels. Additionally, 2,000 and 4,000 mg/kg Galgeun-tang significantly increased urinary bilirubn and protein levels of male and female rats, which were restored during the recovery period. Conclusions: The no-observed-adverse-effect level of orally administered Galgeun-tang was 4,000 mg/kg in both female and male rats, and no target organs were identified. In addition, 400 mg/kg was found to be the no-observed-effect level for toxicity under the study conditions.

• Development and Reproduction
• /
• v.13 no.4
• /
• pp.321-327
• /
• 2009

This study aimed to examine the testis toxicities of metal compound, manganese (Mn), which may be generated as mist or fume in the industrial sites. As well as serum prolactin (PRL) concentration was analyzed because Mn accumulation in basal ganglia up-regulates serum PRL and hyperprolactinemia consecutively induces the testis toxicity. Male F344 rats were divided into the 4 groups (2 controls and 2 Mn treated groups, n=10) on the basis of the test condition (inhalation, Mn $1.5mg/m^3$ or not) and treatment period (for 4-weeks and 13-weeks). The treatment time was 6 hr. a day, 5 days a week for the whole body. Basic tests including changes in body weight, feed rate were observed. Blood and testis Mn concentration, and testis toxicity test such as the number and deformity test of sperm were also observed. Serum PRL level was analyzed by ELISA to certify the relationship between the Mn induced increase of the serum PRL level and sperm production. Blood and testis Mn concentrations were significantly and dose-dependently increased. Sperm count was decreased in Mn-treatment groups than control in a treatment time dependent manner. Morphological analysis of cauda epidydimal sperm showed that the frequencies of morphologically abnormal sperms such as bent tail and small head were increased in the both Mn-treatment groups than control. A significant increase in serum PRL levels was found in response to Mn treatment but it was not hyperprolactinemia range. These results suggest that treatment of Mn up-regulates the serum PRL concentration and induces the testis toxicity. The No Aversed Effect Level (NOAEL) of inhaled Mn on the male rat testis may be under the $1.5mg/m^3$.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.17 no.3
• /
• pp.181-191
• /
• 2007

With the 2-Butanethiol, which is an unidentified inhalation toxic material, acute inhalation toxicity was tested with SD rats. The $LC_{50}$ was evaluated to be 2,500 ppm (9.22 mg/L) or higher which falls under the criteria of acute toxicity Category 3 (500<$LC_{50}$<2,500 ppm) in the Industrial Safety and Health Act. In the subchronical inhalation toxicity test by 0, 25, 100, and 400 ppm, 6 hours a day, 5 days a week, for 13 weeks repeated exposure, though no death or particular clinical presentation was observed, in the female 25 and 400 ppm group, including weight change, and in each concentration group including 400 ppm, change of feed rate, eye stimulation, motility change in male group, and lesions in blood and blood biochemical were observed. In the internal organs weight, 25, 100, and 400 ppm groups in male and 400 ppm group in female showed significant (p<0.05) changes in kidney, liver, thymus, and lung. In the pathological tissue test, severe cortical tubular hyaline droplets were observed in the male 400 ppm group, and all male rats of 400 ppm group and 2 female individuals showed tubular degeneration/regeneration accompanied with pigmentation, showing that the target organs of inhalation exposure of 2-Butanethiol are spleen, kidney, nasal cavity, and adrenal. Through the tests, the NOEL of 2-Butanethiol was evaluated to be 25 ppm (0.092 mg/L) or less for both male and female.