• Journal of Life Science
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• 제19권9호
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• pp.1309-1313
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• 2009

Endocrine disruptors are chemicals which can be found in our normal daily lives. Chemicals such as bisphenol A, DDT, benzophenone and phenylphenol can be easily ingested through plastic food containers and pesticides. Endocrine disruptors can be very harmful and toxic because they disrupt the normal function of the endocrine system. It has been reported that endocrine disruptions can cause fatal strikes in the cardiovascular, reproductive, and central nervous systems, and other parts of the body. Therefore we examined if benzophenone as an endocrine disruptor inhibits development in or induces malformation of chick embryos. Chick embryos which received a single injection of benzophenone ($1{\mu}g$/egg $\sim$ $500{\mu}g$/egg) via the yolk sac at designated times (6, 9, 12, 15, 18 and 21 days after incubation) were investigated. Body weight reduction was observed in middle doses ($40{\mu}g$/egg $\sim$ $60{\mu}g$/egg). High mortality rates and teratogenic signs such as abnormal wry beak and abnormal eyeballs were seen in high doses ($80{\mu}g$/egg $\sim$ $500{\mu}g$/egg). In conclusion, it is suggested that benzophenone induces malformation of chick embryos and seriously inhibits development.

• Reproductive and Developmental Biology
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• 제32권3호
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• pp.141-146
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• 2008

To search a new porcine pheromonal odorant, the models of four type (2D-QSAR, HQSAR, CoMFA & CoMSlA) were derived from quantitative structure-activity relationship (QSAR) between tetrahydrofuran-2-yl family compounds and their observed binding affinity constants (Obs.p$[Od]_{50}$). The optimized CoMFA model (predictability; $r^{2}_{cv.}(q^2)$=0.886 & correlation coefficient: $r^{2}_{ncv.}$=0.984) from ligand based approaches was confirmed as the best model among them. The $N^{1}$-allyl-$N^{2}$-(tetrahydrofuran-2-yl)methyl)oxalamide (P1), 2-(4-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P5) and 2-(3-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P6) molecules predicted as porcine pheromonal odorant by the CoMFA model were showed relatively high binding affinity constant values (Pred.p$[Od]_{50}=8{\sim}10$) and very lower toxicity values against some sorts of toxicity.

• Biomolecules & Therapeutics
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• 제26권5호
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• pp.512-519
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• 2018

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

• Journal of Food Hygiene and Safety
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• 제22권1호
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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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• 제35권2호
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• pp.103-117
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• 2019

The mixture of 5-chloro-2-methylisothiazol-3(2H)-one (CMIT) and 2-methylisothiazol-3(2H)-one (MIT), CMIT/MIT, is a preservative in cosmetics. CMIT/MIT is a highly effective preservative; however, it is also a commonly known skin sensitizer. Therefore, in the present study, a risk assessment for safety management of CMIT/MIT was conducted on products containing 0.0015% of CMIT/MIT, which is the maximum MIT level allowed in current products. The no observed adverse effect level (NOAEL) for CMIT/MIT was 2.8 mg/kg bw/day obtained from a two-generation reproductive toxicity test, and the skin sensitization toxicity standard value for CMIT/MIT, or the no expected sensitization induction level (NESIL), was $1.25{\mu}g/cm^2/day$ in humans. According to a calculation of body exposure to cosmetics use, the systemic exposure dosage (SED) was calculated as 0.00423 mg/kg bw/day when leave-on and rinse-off products were considered. Additionally, the consumer exposure level (CEL) amounted to $0.77512{\mu}g/cm^2/day$ for all representative cosmetics and $0.00584{\mu}g/cm^2/day$ for rinse-off products only. As a result, the non-cancer margin of safety (MOS) was calculated as 633, and CMIT/MIT was determined to be safe when all representative cosmetics were evaluated. In addition, the skin sensitization acceptable exposure level (AEL)/CEL was calculated as 0.00538 for all representative cosmetics and 2.14225 for rinse-off products; thus, CMIT/MIT was considered a skin sensitizer when all representative cosmetics were evaluated. Current regulations indicate that CMIT/MIT can only be used at concentrations 0.0015% or less and is prohibited from use in other cosmetics products. According to the results of this risk assessment, the CMIT/MIT regulatory values currently used in cosmetics are evaluated as appropriate.

• Proceedings of the Korean Environmental Health Society Conference
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• 한국환경보건학회 2004년도 International Conference Global Environmental Problems and their Health Consequences
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• pp.185-187
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• 2004

The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP showed significant organ weight changes in liver, spleen exposed during lactational periods. But the dams exposed during lactational periods showed significant organ weight changes not only in liver, spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However no clear synergistic effects of BPA and BBP could be found. Estrogen receptor ${\alpha}$ expression by BPA and BBP in the uterus(dam, F1 female) and testis(F1 male) were studied. There was no significant different $ER{\alpha}$ expression pattern between control and treated groups. But $ER{\alpha}$ expression were increased in F1 male testis and female uterus. F1 male showed distinct $ER{\alpha}$ expression, especially in the group of lactational combined exposure. Synergistic $ER{\alpha}$ expression was found by combined treatment of BPA and BBP.

• Toxicological Research
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• 제21권1호
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• pp.23-29
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• 2005

A developmental study of CONP01, a new antiarthritic agent, was conducted in Sprague-Dawley rats. Dosage of CONP01 0, 111, 333, and 1000 mg/kg/day were administered to dams orally from day 6 to day 16 of gestation. Two-third of dams per group were subjected to caesarean section on day day 20 of pregnancy for examination of their fetuses, and the remaining one-third of dams per group were allowed to deliver naturally for postnatal examination of their offspring. There was no change in the dams body weights, food consumptions, specific clinical sings and gross findings. There was significant decrease only in the absolute and relative weights of right ovary in 111 mg/kg treatment group, when compared with the vehicle control, whereas other organ weights were not changed. Moreover, no increase in the frequencies of external, visceral and skeletal malformation of fetuses were observed in the treated groups. These results suggest that the oral NOAEL (no observed adverse effect level) of CONP01 may be over 1,000 mg/kg in dams and fetuses of rats.

• Korean Journal of Veterinary Research
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• 제48권3호
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• pp.347-355
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• 2008

Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, is persistent organic pollutants widely spread throughout the environment and human population. But little is known about the adverse biological effects of the PFOA. In the present study, the toxicological effects of PFOA were investigated in rats. Sprague-Dawley rats (N = 10 in each group) were orally administered with PFOA in drinking water for 4 weeks (0, 100, 200, or 400 ppm in male, and 0, 200, 400, or 800 ppm in female). Three female rats given 800 ppm died during the study. PFOA treatment decreased the body weight gain and increased the liver weights in both genders. Serum biochemical investigations revealed significant increases in the aspartate aminotransferase, alanine transaminase, alkaline phosphatase, blood urea nitrogen, total cholesterol, and total bilirubin in male but in female. Serum estradiol (E2) levels were increased in all treated rats. Histopathologically, hepatocellular hypertrophy around central vein was noted in the liver of treated rats. No significant histopathological changes were noted in other organs. In conclusion, PFOA induced toxicological changes in the liver and increased serum E2 level which was not related to histopathological changes of endocrine and reproductive system.

• Archives of Pharmacal Research
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• 제28권1호
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• pp.100-105
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• 2005

Mancozeb (MCZ) is known to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine peritoneal macrophages through evaluation of MCZ-induced alteration of nitric oxide (NO) production and tumor necrosis $factor-{\alpha}(TNF-\alpha)$ synthesis. Macrophages were examined ex vivo from mice orally treated with various doses of MCZ for 5 consecutive days per week for 4 weeks (subacute exposure, 250, 1000, 1500 mg/kg/day) followed by culture for 2 $(TNF-{\alpha})$ or 3 days (NO) in the presence of LPS plus $IFN-{\gamma}$. Macrophages from naive mice were also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2 ${\mu}g//mIL$ in the presence of LPS plus $IFN-{\gamma}$ for 2 $(TNF-{\alpha})$ or 3 days (NO) in vitro. NO production was decreased with the in vitro exposure to all concentrations of MCZ. However, the amount of NO production by peritoneal macrophages from MCZ-subacutely exposed mice was increased in comparision with that of control group. In vitro, MCZ suppressed $(TNF-\alpha)$ secretion with significant reduction at 2 ${\mu}g/mL$ MCZ. Conversely, $(TNF-{\alpha})$ release was enhanced ex vivo. This study provides the substantial evidence on MCZ-induced alternation in macrophage activity. In order to clearly understand the contrasting effect of MCZ on peritoneal macrophage activity, it is necessary to further investigate the influence of major metabolite of MCZ (ETU) exposure on the NO production and $(TNF-{\alpha})$ synthesis.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• 제27권2호
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• pp.97-104
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• 2017

Objectives: This study aims to suggest definitions in accordance with the purpose of the permissible limit system in order to suggest criteria for substances with permissible exposure limits and expanded candidate substances under the Occupational Safety and Health Act in Korea. Methods: The occupational safety and health related acts from six countries were researched, including from Korea. To understand the health hazards of substances with permissible exposure limits, health hazards were prioritized for 211 substances through working environment measurement on the basis of KOSHA's preceding research. Results: To suggest criteria for substances with permissible exposure limits and expanded candidate substances, definitions were suggested in accordance with the purpose of the permissible limit system. Based on the health hazard priorities for the working environment, selection criteria were identified. Conclusions: Three suggestions for substances with permissible exposure limits were proposed including substances where occurred serious health hazards such as carcinogenicity, germ cell mutagenicity, and reproductive toxicity to workers.