• Toxicological Research
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• 제26권1호
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• pp.67-74
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• 2010

The present study was conducted to obtain information on the effects of amitraz on reproductive and developmental parameters in rats. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and up to lactational day 4. During the study period, clinical signs, body weights, food intake, organ weights, reproductive and littering findings, necropsy findings, sperm parameters, and histopathology were examined. At 360 ppm, decreases in the body weight gain, food consumption, and the number of live pups and an increase in the post-implantation loss were observed. In addition, decreases in the seminal vesicle weight and sperm motility were found in males. At 120 ppm, a decrease in the food consumption was found transiently in both males and females, but no reproductive and developmental toxicity was observed in both sexes. There were no signs of either general or reproductive and developmental toxicity in the 40 ppm group. Based on these results, it was concluded that the repeated oral administration of amitraz to rats resulted in a decrease in the food consumption at 120 ppm and decreases in the seminal vesicle weight, sperm motility, and the number of live pups and an increase in the post-implantation loss at 360 ppm in rats. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz for general and reproduction/developmental toxicity was believed to be 120 ppm, and the no-observed-effect level (NOEL) of amitraz was believed to be 40 ppm in rats.

• Toxicological Research
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• 제21권3호
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• pp.263-269
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• 2005

This study was performed to investigate repeated-dose toxicities of Clean natural, a new disinfectant, in Sprague-Dawley(SD) rats. In the 4-week repeated oral toxicity study, Clean Natural was orally administered once daily via gavage to male and female rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg body weight for 4-weeks. There were no deaths and clinical signs during the dosing period. In both sexes, there were no statistically significant differences between the administered and control groups in urinalysis indicators and hematological parameters. In serum biochemistry, aspartate aminotransferase(AST) was significantly decreased and sodium content was increased in the 2,000 mg/kg male group, while chlorine was significantly decreased in the 2,000 mg/kg female group. Also, albumin, total cholesterol and total bilirubin were significantly increased in the 2,000 mg/kg male and female group. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver was observed in the 2,000 mg/kg male and female groups. And pigmentation in the spleen was observed in the 2,000 mg/kg male group. In conclusion, four-week repeated oral dose of Clean Natural to rats did not cause apparent toxicological change at the dose less than 2,000 mg/kg body weight. Thus it is suggested that no-observed adverse-effect level(NOAEL) for Clean Natural in rats was considered to be 1,000 mg/kg/day.

• 한국환경과학회지
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• 제25권4호
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• pp.505-516
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• 2016

With the development of nanotechnology, nanomaterials are used in various fields. Therefore, the interest regarding the safety of nanomaterial use is increasing and much effort is diverted toward establishment of exposure assessment and management methods. Occupational exposure limits (OELs) are effectively used to protect the health of workers in various industrial workplaces. This study aimed to propose an OEL for domestic multi-walled carbon nanotubes (MWCNTs) based on animal inhalation toxicity test. Basic procedure for development of OELs was examined. For OEL estimation, epidemiological study and quantitative risk assessment are generally performed based on toxicity data. In addition, inhalation toxicity data-based no observed adverse effect level (NOAEL) and benchmark dose (BMD) are estimated to obtain the OEL. Three different estimation processes (NEDO in Japan, NIOSH in USA, and Baytubes in Germany) of OELs for carbon nanotubes (CNTs) were intensively reviewed. From the rat inhalation toxicity test for MWCNTs manufactured in Korea, a NOAEL of $0.98mg/m^3$ was derived. Using the simple equation for estimation of OEL suggested by NEDO, the OEL of $142{\mu}g/m^3$ was estimated for the MWCNT manufacturing workplace. Here, we used test rat and Korean human data and adopted 36 as an uncertainty factor. The OEL for MWCNT estimated in this work is higher than those ($2-80{\mu}g/m^3$) suggested by previous investigators. It may be greatly caused by different physicochemical properties of MWCNT and their dispersion method and test rat data. For setting of regulatory OELs in CNT workplaces, further epidemiological studies in addition to animal studies are needed. More advanced technical methods such as CNT dispersion in air and liquid should be also developed.

• Toxicological Research
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• 제31권4호
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• pp.403-414
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• 2015

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

• Toxicological Research
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• 제33권1호
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• pp.15-23
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• 2017

Acanthopanax divaricatus (Siebold & Zucc.) Seem. var. albeofructus (ADA), a traditional medical herb, has been used to treat arthritis and muscular injury, to strengthen muscle and bone, and to get vital energy. However, information regarding its toxicity is limited. ADA was administered by oral gavage to groups of rats at doses of 0 (control), 1,000, 1,500, 2,000, 2,500, and 3,000 mg/kg five times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, organ weights, necropsy, histopathological finding, vaginal cytology, and sperm morphology were compared between control and ADA-treated groups. Salivation was intermittently observed in both sexes receiving 2,500 and 3,000 mg/kg directly after dosing. Absolute liver weights increased in females receiving 2,000, 2,500, and 3,000 mg/kg ADA (P < 0.05, P < 0.01, and P < 0.01, respectively) and so did the relative liver weights (P < 0.001). Salivation and increased liver weight were ADA-related changes but not considered to be adverse effects. Salivation was intermittent and transient, and the liver weight increase was minor and not accompanied by other changes such as hepatic morphological or functional alterations. The no-observed-adverse-effect-level was determined to be at least 3,000 mg/kg in both sexes of rats.

• Toxicological Research
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• 제14권2호
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• pp.261-271
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• 1998

The acute and subacute toxicity of New Wonbangwoohwangchungsimwon (NSCH) which was used l-muscone as substitutive material of musk were investigated in S.D. rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with five dosages of 0, 500, 710, 1,000, 1,410 and 2,000 mg/kg. Body weights were significantly decreased at 500 and 710 mg/kg dose group in male and abnormal autopsy findings were founded in both sexes at all dose. Intraperitoneal $LD_{50}$ of NSCH was 1,088.3 mg/kg in male and 1159.3 mg/kg in female rats. In the subacute toxicity study, NSCH was administrated orally to both sexes of rats for 4 weeks as several doses(0, 320, 800, and 2,000 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 analysis, and other findings. Above data strongly suggest that no observed adverse effect level of NSCH might be over 2,000 mg/kg/day in this study.

• Toxicological Research
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• 제14권2호
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• pp.237-248
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• 1998

The acute and subacute toxicity of New Woohwangchungsimwon(NWCH) which was used l-muscone as substitutive material of musk were investigated in S.D. rats. In intraperitoneal acute toxicity test. rats(Sprague-Dawley, SPF) were injected intraperitoneally with dosages of 0, 540, 750, 1,070, 1.500 and 3,000 mg/kg. Body weights were significantly decreased at 540 mg/kg dose group in both sexes and abnormal autopsy findings were founded in both sexes at all treated groups. Intraperitoneal $LD_{50}$ of NWCH was 812.3 mg/kg in male and 872.3 mg/kg in female rats. In the subacute toxicity study, NWCH was administrated orally to both sexes of rats for 4 weeks as several doses(0, 320, 800 and 2, 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 analysis, and other findings. Above data strongly suggest that no observed adverse effect level of NWCH might be over 2,000 mg/kg/day in this study.

• Biomolecules & Therapeutics
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• 제11권3호
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• pp.200-203
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• 2003

The present study was carried out to investigate the potential acute toxicity of bamboo leaf water extract by a single oral dose in Sprague-Dawley rats. Twenty male and female rats aged 5 weeks were randomly assigned to four groups of 5 rats each and were administered singly by gavage at dose levels of 0, 1250, 2500, or 5000 mg/kg body weight. Mortalities, clinical findings, and body weight changes were monitored for the l4-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. Throughout the study period, no treatment-related deaths were observed. There were no adverse effects on clinical signs, body weight, and gross finding at any dose tested. The results showed that the single oral administration of bamboo leaf water extract did not induce any toxic effect at a dose level of below 5000 mg/kg in rats and that the minimal lethal dose were considered to be over 5000 mg/kg body weight for both sexes.

• 동의생리병리학회지
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• 제23권4호
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• pp.848-852
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• 2009

Taeumjowi-tang is originated in Donguisusebowon edited by Lee Je-Ma. The objective of this study was to investigate the subacute toxicity of Taeumjowi-tang in rats. Several doses(0, 125, 250, 500, 1,000, and 2,000 mg/kg) of Taeumjowi-tang were administered to rats for 4 weeks. The mortality, clinical signs, body weights and gross findings were examined for experimental period. No dead animals were found during the experimental period. In addition, any differences were not found between control and treated groups in clinical signs, hematology, serum biochemistry, and other findings. In conclusion, the no observed adverse effect level(NOAEL) for Taeumjowi-tang was over 2,000 mg/kg/day in rats.

• 대한수의학회지
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• 제45권1호
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• pp.29-37
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• 2005

13-week orally repeated dose toxicity was investigated to ascertain the toxic effects of Aristolochiae radix in F344 rats at dose levels of 0, 1 (0.003 AA, aristolochic acid, mg/kg), 5 (0.014 AA mg/kg), 25 (0.068 AA mg/kg), 125 (0.34 AA mg/kg), and 500mg/kg (AA 1.36 mg/kg). No mortalities were found in any of the dose groups including vehicle control groups of both sexes during the study period. Hematologic and serum biochemical examinations revealed no changes related to the test item in any of the dose groups of both sexes. However, gross findings at necropsy implicated thickening of the stomach wall. In histopathological examinations, prominent findings related to the test item treatment were observed in the stomach and urinary bladder. There were squamous cell papilloma, squamous cell hyperplasia, ulceration and erosion observed in the non-glandular stomach. Squamouse cell hyperplasia was observed at dose levels of more than 125 mg/kg in both sexes and squamous cell papilloma was observed at dose level of 500 mg/kg in both sexes. The incidence and severity of these proliferating lesions including squamous cell hyperplasia and squamous cell papilloma increased with dose dependency. Transitional cell hyperplasia was also observed in the urinary bladder at dose levels of more than 25 mg/kg in both sexes and the incidence and severity of the lesion increased with dose dependency. In conclusion, the toxic changes related to the test item treatment were observed in the stomach and urinary bladder, and the no-observed-adverse-effect level (NOAEL) was estimated to be 5 mg/kg/day for both males and females in F344 rats.