• Journal of Ginseng Research
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• v.43 no.2
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• pp.242-251
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• 2019

Background: Korean Red Ginseng has been widely used in traditional oriental medicine for a prolonged period, and its pharmacological effects have been extensively investigated. In addition, Angelica gigas and deer antlers were also used as a tonic medicine with Korean Red Ginseng as the oriental herbal therapy. Methods: This study was conducted to evaluate the potential toxicological effect of KGC-HJ3, Korean Red Ginseng with angelica gigas and deer antlers, on reproductive and developmental functions including fertility, early embryonic development, maternal function, and embryo-fetal development. KGC-HJ3 was administered by oral gavage to Sprague-Dawley rats (22 animals per sex per group) at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on fertility and early embryonic development. In addition, KGC-HJ3 was also administered by oral gavage to mating-proven Sprague-Dawley rats (22 females per group) during the major organogenesis period at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on maternal function and embryo-fetal development. Results and conclusion: No test item-related changes in parameters for fertility, early embryonic development, maternal function, and embryo-fetal development were observed during the study period. On the basis of these results, it was concluded that KGC-HJ3 did not have toxicological potential on developmental and reproductive functions. Therefore, no observed adverse effect levels of KGC-HJ3 for fertility, early embryonic development, maternal function, and embryo-fetal development is considered to be at least 2000 mg/kg/day.

• Toxicological Research
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• v.18 no.2
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• pp.167-174
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• 2002

Historical control data have been shown to be valuable in the proper interpretation and validation of reproductive toxicology studies. The present data were compiled from rat fertility and early embryonic development studies conducted at Korea Institute of Toxicology during the 1994∼2001 period. These data were assembled in order to provide background information for the general and reproductive data collected in 11 fertility and early embryonic development studies using Sprague-Dawley rats obtain-ing from the Breeding Facility, Korea Institute of Toxicology, Korea. A total of 274 males and 274 females were used in these studies during the eight-year period. Parameters of fertility and early embryonic development included clinical sign, body weights, food consumption, organ weights, estrus cycle, copulation index, precoital time, fertility index, pregnancy index, sperm parameters, and early embryonic development parameters. Most of the values were comparable to the previous historical control data reported by other investigators. These data can be wed not only as a historical data base for the meaningful interpretation of data from reproductive and developmental toxicity studies, but also as a contribution to biological characterization of Sprague-Dawley rats.

• Toxicological Research
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• v.27 no.3
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• pp.143-147
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• 2011

Cadmium is considered one of the most toxic, non biodegradable heavy metal for the human and animals. The purpose of the present study was to investigate the changes in biochemical parameters of blood and accumulation of cadmium in various tissue caused by various levels of dietary cadmium chloride ($CdCl_2$) in broiler chicks. $CdCl_2$ was administered through drinking water to broiler chicks. In spectral analysis, $CdCl_2$ treatment caused a significant increase in Glutamate pyruvate transaminase (GPT), creatinine and uric acid levels in all treated groups. Intriguingly, the GPT, creatinine, and uric acid levels were significantly higher at 75 mg/kg as compared to the groups treated with high doses (100, 125 and 150 mg/kg) of $CdCl_2$. Atomic Absorption Spectrophotometer (AAS) was used for the determination of Cd accumulation in kidney, liver and Breast muscles. AAS analysis revealed that Cd accumulation is increased in breast muscles as compared to liver and kidney at higher doses of Cd than 75 mg/kg.

• Toxicological Research
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• v.11 no.2
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• pp.199-203
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• 1995

The focus of this study was to investigate that cellular parameters and glucose uptake might be altered by extracellular calcium and starvation. Addition of 1 mM $Ca^{++}$ to hepatocytes (equalling to the free calcium concentration of blood) significantly increased intracellular $Na^+$ and decreased $Na^+$ & LDH leakage. This pertains to the hepatocytes of control rats as well as those of rats fasted for 24 and 48. hr. These effects might be come from the membrane-stabilizing effects of calcium. But calcium had no effects on cell volumes, superoxide-formation and glucose uptake. Actually hepatocytes of starved rats showed changes in several cellular parameters. Starvation increased LDH leakage, glucose uptake and the total concentration of $Na^+$ and $Na^+$ whereas it markedly decreased cell volumes. Since total tonicity remained unchanged, intracellular $Na^+$ and $Na^+$ could contribute to a higher share of total osmolarity in starvation. Starvation increased the cytoplasmic pH because $R-NH^{3+}$ions and their corresponding counterions disappeared. This increase may be related to suppress the protonization of amino groups in proteins. Starvation decreased hepatic glycogen, a major compound that affects cytosolic volume of hepatocytes. The data indicate that starvation increases the glucose transport activity. The possible molecular basis will be discussed.

• Toxicological Research
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• v.35 no.1
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• pp.65-74
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• 2019

Tetrahydrocurcumin (THC) is a major metabolite of curcumin, which is obtained from Curcuma longa. THC has various benefits and overcomes the bioavailability issue of curcumin. To establish it as a pharmacologically active molecule, its safety profile has to be determined. Thus, the present study aimed to determine the preclinical safety profile of THC in a 90-day subchronic and reproductive/developmental toxicity study in Wistar rats. THC at oral doses of 100, 200, and 400 mg/kg was administered daily for 90 days. Rats in the recovery group were kept for 14 days after treatment termination. The animals were observed for treatment-related morbidity, mortality, and changes in clinical signs, clinical pathology, and histopathology. In the reproductive/developmental toxicity study, THC at 100, 200, and 400 mg/kg was administered orally to rats and the reproductive/developmental parameters in adult male and female rats and pups were observed. THC at up to 400 mg/kg/day of did not have any significant effect on all parameters in male and female rats in both toxicity studies. Thus, 400 mg/kg/day can be considered as the no-observed-adverse-effect-level of THC in rats.

• Toxicological Research
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• v.32 no.4
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• pp.317-325
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• 2016

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague-Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail-Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histo-morphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

• Toxicological Research
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• v.33 no.1
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• pp.25-30
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• 2017

Saccharin, the first artificial sweetener, was discovered in 1879 that do not have any calories and is approximately 200~700 times sweeter than sugar. Saccharin was the most common domestically produced sweetener in Korea in 2010, and it has been used as an alternative to sugar in many products. The interaction between artificial sweeteners and drugs may affect the drug metabolism in patients with diabetes, cancer, and liver damage, this interaction has not been clarified thus far. Here, we examined the effects of the potential saccharin-drug interaction on the activities of 5 cytochrome P450 (CYPs) in male ICR mice; further, we examined the effects of saccharin (4,000 mg/kg) on the pharmacokinetics of bupropion after pretreatment of mice with saccharin for 7 days and after concomitant administration of bupropion and saccharin. Our results showed saccharin did not have a significant effect on the 5 CYPs in the S9 fractions obtained from the liver of mice. In addition, we observed no differences in the pharmacokinetic parameters of bupropion between the control group and the groups pretreated with saccharin and that receiving concomitant administration of saccharin. Thus, our results showed that saccharin is safe and the risk of saccharin-drug interaction is very low.

• Korean Journal of Food Science and Technology
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• v.29 no.4
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• pp.800-803
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• 1997

The acute toxicity of palatinose and palatinose syrup was assessed in Sprague-Dawley rats. Palatinose and palatinose syrup, when administered orally at the doses of 27 g/kg, did not cause any death. Although the decrease in weight gain was observed in males treated with palatinose syrup, it did not have any toxicological importance. There were no significant changes in hematological and biochemical parameters. From these results, it was concluded that palatinose and palatinose syrup did not induce any remarkable toxicological symptoms and the $LD_{50}$ is >27 g/kg by oral administration in Sprague-Dawley rats.

• Toxicological Research
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• v.21 no.3
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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.

• Toxicological Research
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• v.33 no.4
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• pp.333-342
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• 2017

Ethyl formate, a volatile solvent, has insecticidal and fungicidal properties and is suggested as a potential fumigant for stored crop and fruit. Its primary contact route is through the respiratory tract; however, reliable repeated toxicological studies focusing on the inhalation route have not been published to date. Therefore, the present study was conducted to investigate the safety of a 90-day repeated inhalation exposure in rats. Forty male and 40 female rats were exposed to ethyl formate vapor via inhalation at concentrations of 0, 66, 330, and 1,320 ppm for 6 hr/day, 5 days a week for 13 weeks. Clinical signs, body weights, food consumption, urinalysis, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathological findings were compared between the control and ethyl formate-exposed groups. Locomotor activity decreased during exposure and recovered afterward in male and female rats exposed to 1,320 ppm ethyl formate. Body weight and food consumption continuously decreased in both sexes exposed to 1,320 ppm ethyl formate from week 1 or 3 compared with the control values. The increases in adrenal weight and decreases in thymus weight were noted in both sexes exposed to ethyl formate at 1,320 ppm. Degeneration, squamous metaplasia of olfactory epithelium in the nasopharyngeal tissue, or both were noted in the male and female rats at 1,320 ppm and female rats at 330 ppm ethyl formate. Taken together, our results indicate that ethyl formate-induced changes were not observed in male and female rats at 330 and 66 ppm, respectively. This indicates that exposure to ethyl formate at concentrations below 66 ppm for 90 days is relatively safe in rats. This is the first report of a full-scale repeated inhalation toxicity assessment in rats and could contribute to controlling occupational environmental hazards related to ethyl formate.