• Asian-Australasian Journal of Animal Sciences
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• v.14 no.3
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• pp.402-413
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• 2001

Food safety is a term broadly applied to food quality that may adversely affect human health. These include zoonotic diseases and acute and chronic effects of ingesting natural and human-made xenobiotics. There are two major areas of concern over the presence of residues of antibiotics in animal-derived foodstuffs with regard to human health. The first is allergic reactions. Some antibiotics, such as penicillins can evoke allergic reactions even though small amounts of them are ingested or exposed by parenteral routes. The second is development of antibiotic resistance in gut bacteria of human. Recently multi-resistant pneumococcal, glycopeptide-resistant enterococci and gram negative bacteria with extended-spectrum $\beta$-lactamases have spread all over the world, and are now a serious therapeutic problem in human. Although it is evident that drugs are required in the efficient production of meat, milk and eggs, their indiscriminate use should never be substituted for hygienic management of farm. Drug should be used only when they are required. In addition to veterinary drugs, environmental contaminants that were contaminated in feed, water and air can make residues in animal products. Mycotoxins, heavy metals, pesticides, herbicides and other chemicals derived from industries can be harmful both to animal and human health. Most of organic contaminants, such as dioxin, PCBs and DDT, and metals are persistent in environment and biological organisms and can be accumulated in fat and hard tissues. Some of them are suspected to have endocrine disrupting, carcinogenic, teratogenic, immunodepressive and nervous effects. The governmental agencies concerned make efforts to prevent residue problems; approval of drugs including withdrawal times of each preparation of drugs, establishment of tolerances, guidelines regarding drug use and sanitation enforcement of livestock products. National residue program is conducted to audit the status of the chemical residues in foods. Recently HACCP has been introduced to promote food safety from farm to table by reducing hazardous biological, chemical and physical factors. Animal Production Food Safety Program, Quality Assurance Programs, Food Animal Residue Avoidance Databank are para- or non-governmental activities ensuring food safety. This topic will cover classification and usage or sources of chemical residues, their adverse effects, and chemical residue status of some countries. Issues are expanded to residue detection methodologies, toxicological and pharmacokinetic backgrounds of MRL and withdrawal time establishments, and the importance of non-governmental activities with regard to reducing chemical residues in food.

• The Korean Journal of Pesticide Science
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• v.14 no.4
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• pp.490-498
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• 2010

Isotianil is a fungicide which has prevention effects against rice blast disease. In order to register this new pesticide, the series of toxicity data on animal testing were reviewed to evaluate its hazards to consumers and to determine its acceptable daily intake. Isotianil was almost excreted by urine and feces. It has low acute oral toxicity while has no skin toxicity and ocular irritation. Its skin sensitization was evaluated as slight. Genotoxicity of parent compound and metabolite was negligible. Chronic toxicity tests on rats and dogs showed changes of hematology, clinical biochemistry and liver weight. It had no reproductive and teratogenic effects. The estimation of Acceptable Daily Intake(ADI) is based on the lowest no-observed adverse effect level (NOAEL). The lowest NOAEL of 2.83 mg/kg bw/day was found in the twelve-months rats study. The NOAEL was based on increased liver weight and treatment-related effect on clinica chemistry finding at the nest higher dose level of 2.83 mg/kg bw/day. Therefore, it is considered appropriated to apply an uncertainty factor of 100 to the NOAEL 2.83 mg/kg bw/day from the rat study, resulting in an ADI of 0.028 mg/kg bw/day.

• Korean Journal of Veterinary Research
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• v.55 no.2
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• pp.133-139
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• 2015

The increasing uses of zinc oxide nanoparticles (nZnO) in industrial and personal care products raise possible danger of using nZnO in human. To determine whether ZnO induces size-dependent anomalies during embryonic organogenesis, mouse embryos on embryonic day 8.5 were cultured for 2 days under 50, 100, and $150{\mu}g$ of nZnO (< 100 nm) or micro-sized ZnO (mZnO; $80{\pm}25{\mu}m$), after which the morphological changes, cumulative quantity of Zn particles, and expressions of antioxidant and apoptotic genes were investigated. Although embryos exposed to $50{\mu}g$ of ZnO exhibited no defects on organogenesis, embryos exposed to over $100{\mu}g$ of ZnO showed increasing anomalies. Embryos treated with $150{\mu}g$ of nZnO revealed significant changes in Zn absorption level and morphological parameters including yolk sac diameter, head length, flexion, hindbrain, forebrain, branchial bars, maxillary process, mandibular process, forelimb, and total score compared to the same dose of mZnO-treated embryos. Furthermore, CuZn-superoxide dismutase, cytoplasmic glutathione peroxidase (GPx) and phospholipid hydroperoxidase GPx mRNA levels were significantly decreased, but caspase-3 mRNA level was greatly increased in nZnO-treated embryos as compared to normal control embryos. These findings indicate that nZnO has severer teratogenic effects than mZnO in developing embryos.

• 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.

• Journal of Radiation Protection and Research
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• v.21 no.4
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• pp.273-284
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• 1996

Embryos and fetuses are more sensitive to various environmental agents than are adults or children. The biological effects such as intrauterine death and malformation are closely connected with prenatal exposure very various agents. The sensitivity of these embryonic/fetal effects depends on the stage of pregnancy. From the viewpoint of fetal development, embryonic and fetal stages can be divided into three stages : Preimplantation, organogenetic and fetal. Each stage corresponds to 0 to 4.5days, 4.5 to 13.5days, and 13.5days of gestation in mice, respectively. Many studies on the biologcal effects of mice irradiated by ${\gamma}-rays$ at various stages during organogenesis and fetal period have been performed. Based on these results, the dose-effect and dose-response relationships in malformations, intrauterine death, or retardation of the physical growth have been practically modeled by the ICRP(International Commission on Radiological Protection) and other international bodies for radiation protection. Many experimental studies on mice have made it clear that mice embryos in the preimplantation period have a higher sensitivity to radiation for lethal effects than the embryos/fetuses on other prenatal periods. However, no eratogenic effects of radiation at preimplantation stages of mice have been described in many textbooks. It has been believed that 'all or none action results' for radiation of mice during the preimplantation period were applied. The teratogenic and lethal effects during the preimplantation stage are one of the most important problems from the viewpoint of radiological protection, since the preimplantation stage is the period when the pregnancy itself is not noticed by a pregnant woman. There are many physical or chemical agents which affect embryos/fetuses in the environment. It is assumed that each agents indirectly effects a human. Then, a safety criterion on each agent is determined independently. The pregnant ICR mice on 2, 48, 72 or 96 hours post-conception (hpc), at which are preimplantation stage of embryos, were irradiated whole body Cesium-gamma radiation at doses of 0.1, 0.25, 0.5, 1.5, and 2.5 Gy with dose rate of 0.2 Gy/min. In the embryos from the fetuses from the mice irradiated at various period in preimplantation, embryonic/fetal mortalities, incidence of external gross malformation, fetal body weight and sex ratio were observed at day 18 of gestation. The sensitivity of embryonic mortalities in the mice irradiated at the stage of preimplantation were higher than those in the mice irradiated at the stage of organogenesis. And the more sensitive periods of preimplantation stage for embryonic death were 2 and 48 hpc, at which embryos were one cell and 4 to 7 cell stage, respectively. Many types of the external gross malformations such as exencephaly, cleft palate and anophthalmia were observed in the fetuses from the mice irradiated at 2, 72 and 96 hpc. However, no malformations were observed in the mice irradiated at 48 hpc, at which stage the embryos were about 6 cell stage precompacted embryos. So far, it is believed that the embryos on preimplantation stage are not susceptible to teratogens such as radiation and chemical agents. In this study, the sensitivity for external malformations in the fetuses from the mice irradiated at preimplantation were higher than those in the fetuses on stage of organogenesis.

• Journal of Food Hygiene and Safety
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• v.13 no.2
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• pp.121-128
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• 1998

Ochratoxin A (OA) is a mycotoxin produced by Aspergillus ochraceus as well as other molds. It is a natural contaminant of mouldy food and feed. OA has a number of toxic effects, the most prominant being nephrotoxicity. Futhermore, OA is immunosuppressive, genotoxic, teratogenic and carcinogenic. OA inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently, lipid peroxidation induced by OA has been reported, indicating that the lesion induced by this mycotoxin could be also related to oxidative pathway. Since it seems impossible to avoid contamination of foodstuffs by toxigenic fungi, detoxification and detoxication of OA are needed. In this study we investigated the protective effects of aspartame (Asp), phenylalanine (Phe), polyphenol 70S (PP) and aloe extract (AE) on the nephrotoxicity induced by subacute exposure to the OA. Asp and Phe are structural analogues of OA. PP, an ingredient of Green Tea and AE have been known as antioxidant and radical scavenger. Phe (40 mg/kg, i.p.) and Asp (25 mg/kg, p.o.) were administered to Sprague-Dawley rats simultaneously with OA (2.0 mg/kg, p.o.) for 2 weeks. PP (200 mg/kg, p.o.) and AE (50 mg/kg, i.v.) were pretreated before administration of OA, for 2 weeks and 3 days, respectively. Using enzymuria, BUN level, creatinemia and histophathologic examination as indices of renal damage, we observed that all of four compounds prevented the nephrotoxic effects induced by OA. It seems that structural analogues of OA such as Asp and Phe have better protective effect on the nephrotoxicity of OA than antioxidants. These results indicate that 1) formation of free radical and lipid peroxidation are likely to be involved in the nephrotoxicity of OA in vivo, 2) Asp, PP and AE might be used for prevention of renal lesions in cases of ochratoxicosis.

• Korean Journal of Environment and Ecology
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• v.20 no.3
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• pp.345-351
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• 2006

This study investigates the toxic effects of $Cd^{2+}$on frog (Rana dybowskii) by the determination of oocyte maturation and development of embryo exposure to different concentrations of the toxicant. The results show that $Cd^{2+}$ concentration of 0.1ppm suppressed the maturation of the oocytes. To examine the reversibility of the inhibitory effects, the oocytes were exposed to the $Cd^{2+}$ only for 3 hours, and then transferred to plain medium and cultured further for 17 hours. The oocytes were recovered from the toxic effect of the $Cd^{2+}$ when they were exposed to 1ppm, but not to 2.5ppm of the $Cd^{2+}$. The development of 2 cell embryos to 32 cell was completely suppressed at 0.1ppm and the longer the embryos were exposed to the $Cd^{2+}$, the more damage appeared to the embryos and the cytolysis of the 32 cell was induced by $Cd^{2+}$ at 0.1ppm. On the other hand, the embryos of blastula stage were cultured 96 hours in presence of the $Cd^{2+}$ at various concentrations and were examined. The rates of mortality and malformed larvae were investigated by probit analysis. From the results of LC$_{50}$ of 0.1ppm and EC$_{50}$ of 0.08ppm, Tl of 5.0 was derived, which indicates $Cd^{2+}$ is to be considered a teratogenic compound. Such specific malformations occurred in 14.3% as spine deformations at the 0.05ppm, in 75.0% as tail deformations at the 0.1ppm, in 66.7% as abdominal deformations at the 0.01ppm and in 26.0% as profound deformations at the 0.1ppm of $Cd^{2+}$ concentration which living embryos were exposed to. $Cd^{2+}$ suppressed growth to head-tail length at 0.1ppm. In conclusion, The study results reveal that $Cd^{2+}$ must be considered highly toxic effect to oocyte maturation and embryonic development.

• Journal of Preventive Medicine and Public Health
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• v.27 no.4 s.48
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• pp.711-734
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• 1994

Among chemical agents in herbicides, dioxin (2, 3, 7, 8-tetrachloro dibenzo-$\rho$-dioxin : TCDD), a chemical contaminant in herbicides sprayed during the Vietnam War has been known to be the major agent causing toxic effects. Approximately 320,000 korean soldiers participated the Vietnam War from 1964 to 1974. Although the potential hazards of the herbicides among Korean veterans exposed were implicated, the problem had not been a public issue until 1991 when Korean veterans were informed U.S. companies, the herbicides manufacturer payed fund, from which a trust fund for New Zealand and Australian Class members were established in 1985. After a series of appeals and demonstration by the Korean Veterans demanding medical care and compensation for their serious health damages, a bill of medical care and compensation for herbicides victims was promulgated in March 1993 and become effective from May 1993, This study was carried out with two major objectives : the first to understand the health problems caused from the herbicides by reviewing literatures published, and the second to examine the nature and extent of health impacts among Korean veterans exposed and to develop valid study methods for the major study by interviewing and reviewing records on a part of veterans (638 persons) registered and completed medical examination in Seoul Veterans Administration Hospital from June to October 1993. The results obtained are as followings: 1. The literature review of 107 papers revealed that 1) Dioxin is teratogenic, carcinogenic and affects almost all organs including nervous, endocrine, and reproductive systems in animal experiments. 2) The diseases showing evidence of causal association were Hodgkin's disease, non-Hodgkin's disease, lung cancer, lymphoma, soft tissue sarcoma, chloroacne and polyneuropathy when judged on the basis of consistency in study results and biological plausibility. 2. Interview and medical record review study on 638 veterans, though limited validity owing to lack of control group, crude estimates of dioxin exposure levels (no biomarkers measurable), and uncertainty of diagnosis, showed that: 1) Most of the study subject's were in their 40's of age and had been dispatched to Vietnam during the period from $1965{\sim}1970$ around one year. 2) Most frequently complained symptoms in medical examination were motor weakness (32%), sensory abnormalities in extremities (23%), skin diseases (22%), and pain in extremities (20%) whereas in Interview they were more frequent in order of skin problem (44%), motor weakness (38%), sensory abnormalities and pain in extremities(17% and 19% each). Kappa indices on the same category of complaints between two sources of information were variable and relatively low. 3) On medical examination, only a part of the 638 subjects had initial impression (442 pts) and final diagnosis (218 pts) suggesting decision making on diagnosis appeared to be difficult even with all available modern medical technologies: in initial impression disorders from peripheral and central neuropathy were predominant whereas in final diagnosis various types of skin disorder were most frequent 4) When dose-response relationship between several conditions (from questionnaire) and arbitrary exposure scores were examined by CMH linear trend test, spontaneous abortion, sexual problems and health problem of offsprings showed statistically significant linear trends. However, pregnancy, accident and suicidal attempts did not show any relationship in this study capacity. 5) Among complaints, psychosis and neurosis (anxiety, phobia) in interview study, and memory disorder and psychosis in medical record study revealed linear trend. 6) Skin disorder was the only condition showing linear trend in initial impression and none in final diagnosis on medical examination. Even though objective to select out dioxin-related disease or group of diseases from this study was not achieved the research experiences provided firm basis for developing various methodological approaches. 3. From this preliminary study we concluded that a larger scale major epidemiologic study on health impacts of herbicides among Korean veterans exposed is not only Indispensible but also well designed study with more valid exposure information and diagnosis may be able to establish causal relationship between certain groups of diseases and exposure to the herbicides among Korean veterans.

• Korean Journal of Poultry Science
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• v.37 no.2
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• pp.139-143
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• 2010

Quail is a very useful animal model for studying vertebrate development because of its small body size and unique reproductive traits. This species is also ideal model for producing germline chimeras via transferring exogenous primordial germ cells (PGCs) into the recipient embryo. To increase the contribution efficiency of donor PGCs into recipients' tissues, decreasing the population of endogenous PGCs has been rate-limiting factor. We therefore conducted this study to investigate if gamma ($\gamma$)-irradiation depletes endogenous PGCs in developing quail embryo. Firstly, freshly laid stage X quail embryos were irradiated with various output of $\gamma$-irradiation and its teratogenic effect on the embryo was evaluated. Although a dose-dependent increase in the number of embryo showing malformation was found as the output increased (0, 250, 500, 750, and 1,000 rads), only a maximum of 10.1% of embryos were abnormal in 1,000 rads. Immunocytochemical analysis using the QCR1 antibody, which is specific marker for quail PGCs, was conducted to analyze the effect of sterilization. As results, $\gamma$-rays at a dose-rate of 500 rads/73 sec onto undeveloped stage X embryo significantly reduced the number of germ cells to an average of 75.55 % and 82.03 % in male and female embryos, respectively. We conclude that $\gamma$-ray selectively targets PGCs while affects minimally to the somatic development in quail embryo. Our results will not only provide important data for germline chimera production but can be used for analyzing the effect of ionized rays on the differentiating germ cells in various stages during animal development.

• Korean Journal of Ecology and Environment
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• v.35 no.3 s.99
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• pp.198-212
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• 2002

A numerical variation and abnormalities were studied on egg bags and embryos of Korean salamander, Hynobius leechii from agricultural habitat. The teratogenic and toxic effects of fungicide benomyl were also investigated with early embryos from non-agricultural habitat. We collected 144 egg bags from agricultural region, and 3418 of early embryos were contained. The lengths of egg bags were varied from 10 to 23 cm and the most frequent length was 19 cm. The number of embryos was varied from 7 to 43, and the most frequent range was 22 to 26. Spontaneous abnormalities were occurred in 406 embryos among 116 egg bags, and 24 kinds of external abnormalities were found. Individuals showing severe external defect were histologically studied and they showed optic dyspalsia, thyroid carcinoma, somatic muscular dysplasia, partial biaxial structure, decrease of red blood cells in the heart, cephalic degeneration and intestinal dysplasia. 385 embryos from non-agricultural region were exposed to 200 nM${\sim}$ 1 ${\mu}$M of benomyl at blastula or gastrula for 12 days. All embryo were dead in the concentration of 1 ${\mu}$M (LD$_{100}$) and 75% of embryos were dead in 800nM of benomyl. Speciflc effect due to benomyl was acrania or cephalic dysplasia and this restult suggests that the benomyl inhibit stongly to the development of neural tissue. These abnormal developments may be caused by antimitotic action, inhibition of tubulin complex, destruction of microtubule, inhibitions of neurulation and closing of neural fold, and by the inhibition of the movement of neural crest cells.