• Toxicological Research
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• v.21 no.4
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• pp.325-332
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• 2005

The developmental toxicity of water extract of licorice (Glycyrrhiza glabra) was evaluated in rats. Licorice extract (500, 1,000 or 2,000 mg/kg) was dissolved in drinking water and orally administered to male rats from 9 weeks before mating to the day of copulation, and to females from 2 weeks before mating to gestational day 19. On gestational day 20, the animals were sacrificed for Cesarian section, and maternal and fetal abnormalities were examined. Licorice extract neither induce clinical signs, nor affect the body weight gain, feed and water intake, estrous cycle, copulation and fertility rates, blood $17\beta-estradiol$ level and organ weights of dams. Also, the implantation and development including body weights, absorption and death of embryos and fetuses were not influenced by in utero exposure to licorice. In addition, there were no increases in external, visceral and skeletal abnormalities of fetuses. Taken together, it is suggested that no observed adverse effect level of licorice extract is higher than 2,000 mg/kg, and that long-term in utero exposure to licorice might not cause developmental toxicities of embryos and fetuses.

• Journal of Food Hygiene and Safety
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• v.22 no.1
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• pp.1-14
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• 2007

The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

• Toxicological Research
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• v.11 no.1
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• pp.81-89
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• 1995

A teratogenicity study of KTC-1, a new semisynthetic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 7, 21, and 63 mg/kg/day were administered to darns orally gayage from day 7 to day 17 of gestation. Two-third of dams per group were subjected to cesarean section on day 21 of pregnancy for examination of their fetuses, and the remaining one-third of darns per group were allowed to deliver naturally for postnatal examination of their offspring. At 21 mg/kg/day, an increase in the skeletal variations of F1 fetuses and a decrease in the body weight of F1 offspring were seen. At 63 mg/kg/day, a loss in body weight was observed in darns. An increase in fetal death rate, a decrease in litter size and body weight, and an increase in the incidence of visceral malforrnations and skeletal variations were found in F1 fetuses. In particular, lumar rib occurred at an incidence of 31%. In addition, an increase in the dead newborns at birth and neonatal deaths during the lactation period, a loss in body weight, and a decrease in spleen weight were observed in F1 offspring. There were no signs of maternal toxicity or embryotoxicity at 7 mg/kg/day. The results suggest that the no-effect dose level(NOEL)for dams is 21 mg/kg/day, and NOELs for F1 fetuses and offspring are 7 mg/kg/day.

• Biomolecules & Therapeutics
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• v.2 no.1
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• pp.82-93
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• 1994

DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of Fl fetuses, as well as growth, behaviour and mating performance of Fl offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in Fl offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and Fl offspring are 0.1 mg/kg/day and NOEL for Fl fetuses is 0.3 mg/kg/day.

• Journal of Yeungnam Medical Science
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• v.35 no.2
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• pp.156-164
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• 2018

Environmental contaminants are one of the important causal factors for development of various human diseases. In particular, the perinatal period is highly vulnerable to environmental toxicants and resultant dysregulation of fetal development can cause detrimental health outcomes potentially affecting life-long health. Perfluoroalkyl compounds (PFCs), emerging environmental pollutants, are man-made organic molecules, which are widely used in diverse industries and consumer products. PFCs are non-degradable and bioaccumulate in the environment. Importantly, PFCs can be found in cord blood and breast milk as well as in the general population. Due to their physicochemical properties and potential toxicity, many studies have evaluated the health effects of PFCs. This review summarizes the epidemiological and experimental studies addressing the association of PFCs with neurotoxicity and immunotoxicity. While the relationships between PFC levels and changes in neural and immune health are not yet conclusive, accumulative studies provide evidence for positive associations between PFC levels and the incidence of attention deficit hyperactivity disorder and reduced immune response to vaccination both in children and adults. In conclusion, PFCs have the potential to affect human health linked with neurological disorders and immunosuppressive responses. However, our understanding of the molecular mechanism of the effects of PFCs on human health is still in its infancy. Therefore, along with efforts to develop methods to reduce exposure to PFCs, studies on the mode of action of these chemicals are required in the near future.

• Applied Microscopy
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• v.30 no.3
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• pp.285-293
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• 2000

The present study has been carried out to investigate the effect of fluoride toxicity on the morphology as well as inorganic chemical constituents of rat teeth. Rats were administered sodium fluoride at dose of 0 ppm, 100 ppm, 200 ppm and 300 ppm at the beginning of pregnancy. Animals were perfused intravascularly with glutaraldehyde and the incisors were removed. Changes in the protein composition of the secretory and maturation enamel were investigated using polyacrylamide gel electrophoresis (SDS PAGE). And the enamel surface of incisors was examined under scanning electron microscope (SEM). Changes of protein quantities were found significantly in high levels fluoride administration for experimental groups compared with control. The SDS PAGE analysis demonstrated as follows In control group, secretory phase enamel protein, amelogenins, was detected more quantities than experimental group. The enamelin, presence in maturation phase enamel , showed more quantifies than control enamel with an increasing fluoride concentration in the drinking water. Also, the scanning electron micrographic data showed hypoplastic, tough, uneven, pitted and cracked enamel surfaces covered with granular deposits as a result of excessive intake of fluoride. From these results we conclude that high dose of fluoride administration leads to severe structural alterations on the enamel surface and these structural changes could be through defective mineralization.

• Korean Journal of Veterinary Research
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• v.34 no.1
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• pp.69-75
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• 1994

Pregnant CD-1 mice were exposed to methylmercury in the drinking water at concentration of 20ppm with subcutaneous treatment of thiaminHCl(vitamin $B_1$) (100mg, 200mg or 300mg/ kg b.w.) or BAL(5.0 mg/kg b.w.) under the alone or combined base at the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters, including body weight and crown-rump length in the mice exposed to mercury, were reduced as placental weight compared to those in the control group(no treatment). The incidence of dead fetuses/resorption and malformed fetuses(especially cleft palate) was also increased even in the group treated with thrapeutic agents as well as in the mercury only treated group. However, all kinds of alteration indicated above, possibly induced by mercury, reduced/or decreased significantly compared to those of control. A subtle indication of maternal toxicity was noted in most experimental animals as evidenced by decreased water consumption and increased relative liver weight. The present study confirmed that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when administered during organogenesis and that thiamin administration may have therapeutic application for the treatment or prevention against of deleterious effects induced by mercury during gestation period.

• Clinical and Experimental Reproductive Medicine
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• v.20 no.2
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• pp.165-176
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• 1993

These studies were carried out to investigate the optimal freezing protocol for 2 cell mouse embryos and to find the probability of quality control with 2-cell embryos frozen. The embryos showed the best survival by the protocol composed of a freezing solution with the cryoprotectants(1.5M propanediol + 0.1M sucrose), and a 2-steop thawing method(room temperature, 20 sec-37$^{\circ}C$, 20 sec). The developmental ability of frozen-thaw 2-cell embryos did not differ from that of fresh 2-cell embryos in m-KRB medium with 0.4% bovine serum albumin. But development of frozen-thaw embryos was depended on the supplements of the medium. In the albumin-free medium, the developmental rate(rate of blastocysts) was significantly reduced, compared with that in the medium with 0.4% BSA. Also, when frozen-thaw embryos were cultured in the meduim with human fetal cord serum(HCS), the developmental rate of frozen-thaw embryos was sligtly reduced, compared with that of fresh 2-cell embryos. Finally, frozen-thaw 2-cell mouse embryos were more sensitive to the toxic agent of disposable-plastic syringe. Therefore, toxicity of medium could be effectively detected by frozen-thaw 2-cell mouse embryos.

• Toxicological Research
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• v.24 no.2
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• pp.137-150
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• 2008

Sexually mature male and female rats were orally intubated with the organophosphorus insecticide, Pestban at a daily dosage of 7.45 or 3.72 mg/kg bwt, equivalent to 1/20 and 1/40 $LD_{50}$, respectively. Male rats were exposed for 70 days, while the female rats were exposed for 14 days, premating, during mating and throughout the whole length of gestation and lactation periods till weaning. The results showed depressed acetylcholinesterase(AChE) activity in the brain of parents, fetuses and their placentae in a dose-dependent manner. The fertility was significantly reduced with increasing the dose in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre-and postimplantation losses were significantly increased. The incidence of resorptions was more pronounced in treated female compared to male group and was dose dependant. The behavioral responses as well as fetal survival and viability indices were altered in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group and occurred in a dose-related manner. The recorded morphological, visceral, and skeletal anomalies were significantly increased with increasing the dose in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to Pestban would cause adverse effects on fertility and reproduction.

• Korean Journal of Agricultural Science
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• v.47 no.3
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• pp.657-665
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• 2020

The objective of this study was to investigate whether supplementation of pentoxifylline (PTX; phosphodiesterase inhibitor) to thawed boar semen improves the post-thaw motility of sperm and affects the efficiency of artificial insemination (AI) and further development. To determine the concentration of PTX for AI, frozen-thawed semen was incubated with 0, 5, 10, and 20 mM PTX in an extender freezing medium, respectively, after thawing. Kinematic properties of sperm were examined with a computer-assisted semen analysis (CASA) system. In addition, viability and mitochondrial activity were also tested by LIVE/DEAD and a MitoTracker kit. There were no significant differences in the kinetic parameters of thawed sperm between control and treatment groups, but overall assessment parameters such as motility and rapid progressive were higher in the 10 mM PTX group. In the viability and mitochondrial assay, there were no significant differences observed in the PTX treatment, compared to the control. For further analysis, artificial inseminations were performed using frozen semen and 10 mM PTX treated cryopreserved semen, respectively. There were no differences in pregnancy rates and fetus weights among the groups until 30 and 40 days, but litter size was reduced and relatively low-birth weight was observed in the PTX group. In summary, our findings suggest that enhancement of in vitro sperm quality or non-toxicity supplemented by PTX may have detrimental effects on fetus development.