• YAKHAK HOEJI
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• v.55 no.2
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• pp.81-90
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• 2011

Most antineoplastic agents are nonselective in their mechanism of action, affecting noncancerous as well as cancerous cells, and resulting in acute effects such as irritation of mucous membranes and chronic effects such as genotoxicity, teratogenicity, and carcinogenicity. Healthcare workers occupationally exposed to antineoplastic agents are at risk. The present study aimed to develop and apply methods to monitor occupational exposure to antineoplastic agents, using cyclophosphamide (CP) as the model compound. To monitor environmental and biological exposure, potentially contaminated surfaces were wiped and 24 hour urine samples were collected from workers. Liquid chromatography combined with tandem mass spectrometry was performed, with a limit of detection of 0.05 ng/ml. Measurable amounts of CP were detected on 92% of the sampled surfaces, with a geometric mean of 175.22 $ng/m^2$. Despite the environmental contamination of the model compound, CP was below the detection limit in all urine samples. If workplace contamination cannot be completely avoided, it is importance to reduce exposure to the lowest possible levels. To this aim, efforts to minimize occupational exposure along with biological and environmental monitoring are required. The standardized sampling techniques, and specific and sensitive analytical methods reported in this study may be helpful in assessing occupational exposure and devising strategies to reduce exposure.

• Korean Journal of Environment and Ecology
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• v.33 no.2
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• pp.178-186
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• 2019

This study used the probit analysis to evaluate the toxicity of three chemicals - benomyl (Germicide), carbofuran (insecticide), and thiobencarb (herbicide) - with the FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol using the incubated embryos of tree frog, Hyla japonica. The results showed that the larval body length decreased while the mortality and malformation rates increased as the concentrations of benomyl, carbofuran, and thiobencarb increased. The teratogenic concentration ($EC_{50}$) of benomyl, carbofuran, and thiobencarb were 1.00, 0.58, 4.75 mg/L, respectively, indicating that the malformation of larvae was the most sensitive to carbofuran. The embryo lethal concentration ($LC_{50}$) was 7.04, 28.71, and 16.12mg/L, respectively, indicating that benomyl showed the lowest embryo lethal concentration. The teratogenic index (TI) was 7.04 in Benomyl, 49.50 in Carbofuran, and 3.39 in Thiobencarb, indicating that the TI values were above 1.5, which is the criterion of teratogenicity, for all three chemicals. All three pesticides examined by this study were considered to be the most teratogenic substances, and the carbofuran was the most potent teratogen.

• Toxicological Research
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• v.35 no.1
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• pp.75-81
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• 2019

Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th-15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 ($3.97{\pm}0.21g$ and $27.3{\pm}0.54mm$, respectively) and 4.5 mg/kg ($3.48{\pm}0.15g$ and $23.22{\pm}1.02mm$, respectively) than in the control group ($4.0{\pm}0.15g$ and $30.01{\pm}0.42mm$, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, respectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats.

• Toxicological Research
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• v.35 no.2
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• pp.119-129
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• 2019

As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

• Journal of Rhinology
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• v.25 no.2
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• pp.103-107
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• 2018

Pregnancy rhinitis is a relatively common condition. It is characterized by the presence of nasal symptoms, especially nasal congestion, not present prior to pregnancy, but typically present during the last 6 or more weeks of pregnancy, without other signs of respiratory tract infection or any known allergic causes, and disappearing completely within 2 weeks after delivery. Nasal saline irrigation, intranasal steroid spray, and oral antihistamines are usually recommended as the first line of treatment for rhinitis. However, most pregnant women refuse medical treatment for pregnancy rhinitis because of the fear of teratogenicity. Severe pregnancy rhinitis increases the risk of snoring, which has been suggested as having adverse effects on the fetus. In cases where the patients are unable to control their symptoms, pregnancy rhinitis can negatively affect the quality of life (QOL) as well as the pregnancy outcome. Therefore, special caution is required for determining the appropriate diagnosis and treatment modalities for pregnancy rhinitis. Here, we report for the first time, the successful treatment of pregnancy rhinitis that was unresponsive to conservative management and medical therapy by using microdebrider-assisted inferior turbinoplasty at the final stages of pregnancy, along with a review of the relevant literature.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.562-569
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• 2022

Etretinate, an acitretin metabolite, has a long retention duration in adipose tissues with a teratogenic potential. FDA advises a contraceptive period of at least three years after discontinuing acitretin. However, the effect of accumulated etretinate in adipose tissues on fetus is unknown. Although the teratogenic threshold for serum concentration of etretinate has been presented as higher than 2 ng/mL, that of acitretin is unknown. To examine factors affecting body retention of acitretin and etretinate, effects of acitretin dosage, acitretin-taking duration, elapsed time after stopping acitretin, age, sex, concomitant alcohol consumption, and foods and supplements rich in vitamin A intake on serum concentrations of acitretin and etretinate were analyzed in 14 acitretin-taken patients and 58 controls without taking acitretin or etretinate. Serum concentrations of acitretin, but not etretinate, tended to be inversely related to the discontinuation duration. They were also related to old age. Different from a published result that alcohol consumption could promote the metabolism of acitretin into etretinate, alcohol intake did not affect serum concentrations of etretinate. Unexpectedly, more frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum acitretin, whereas less frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum levels of etretinate in acitretin-taken patients. Despite preliminary data, inter-individual variations in serum retention of etretinate suggest the necessity of further research before applying the same guidelines to everyone to minimize unnecessary contraception.

• Herbal Formula Science
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• v.31 no.1
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• pp.21-28
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• 2023

Objective : Scolopendra, a dried body of Scolopendra subspinipes mutilans, is one of Korean medicine. Several reports revealed that Scolopendra has therapeutic effects for arthritis, neuroinflammatory diseases and neuropathic pain. However, the fetal adaptive response or teratogenicity associated with administration of Scolopendra is unclear. Therefore, this study aimed to investigate the fetal toxicity effects that were induced following oral administration of Scolopendra water extract (SWE) in pregnant mice. Methods : The pregnant mice were administrated SWE at dosed of 0, 100, 500 and 1000 mg/kg/day during gestation day 0-18. The mortality, body weight and clinical signs of pregnant mice were observed throughout experimental period. Also, the mortality and malformations in foetus were examined. Results : No meaningful changes were observed in the mortality and clinical signs of pregnant mice between the normal control group and SWE administrated groups. Additionally, there are no significant changes in fetal mortalities, and malformations by SWE administration. conclusion : These results suggest that oral exposure to SWE during pregnancy at oral dosages up to 1000 mg/kg/day did not induce teratogenic toxicity in regard to fetal mortality and morphology.

• Korean Journal of Environmental Biology
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• v.33 no.4
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• pp.425-432
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• 2015

Pollution in the fresh water system in urban area has the adverse effect on the amphibians population. Restoration activity of amphibian in the urban stream has been growing in Korea as well as western country. For successful restoration water quality of urban stream should be sufficient for survival and normal development of amphibian. To monitor the biological safety of surface water in the Tancheon basin, the capital area of Korea, a 6-day exposure Bombina orientalis embryo developmental toxicity assay was examined. The toxicity of surface water of Tancheon mainstream were lower than those of tributaries of Tancheon. The survival rate of embryos negatively correlated with total dissolved solid, turbidity and electrical conductivity whereas the developmental abnormality and growth retardation of embryos was positively correlated with total dissolved solid, turbidity and electrical conductivity. An amphibian developmental toxicity assay would be helpful for the selection of point for construction of habitat and reintroduction of amphibian in interrupted urban stream.

• Korean Journal of Environment and Ecology
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• v.34 no.3
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• pp.207-215
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• 2020

In this experiment, investigated toxicity evaluation of chemicals using Asian toad embryos, along FETAX(Frog Embryo Teratogenesis Assay-Xenopus) protocol. Asian toad, Bufo gargarizans embryo incubated and investigation of Benomyl(Germicide), Carbofuran(Insecticide) and Thiobencarb(Herbicide) effect by probit analysis. As a result, depends on the concentrations of Benomyl, Carbofuran and Thiobencarb, along mortality and malformation rates were increases and larval body length were decreased. The teratogenic concentration(EC₅₀) of Benomyl, Carbofuran and Thiobencarb were 1.03, 8.74, 4.98mg/ℓ, respectively. And when exposed to Benomyl, larvae responded most sensitively to malformations. Embryo lethal concentration (LC₅₀) Benomyl, Carbofuran and Thiobencarb were 7.26, 560.72, 16.87mg/ℓ, respectively. And Benomyl were at the lowest concentration of lethal the embryos. The teratogenic index(TI) were 7.05 in Benomyl, 64.16 in Carbofuran and 3.39 in Thiobencarb, thus TI values were above 1.5, which is the criterion of teratogenicity. Three of the pesticides used in this study were considered to be a teratogenic substances and Carbofuran was the most potent teratogen. And more specific researches are needed to investigate the effects of pesticides on the embryo development of toads and amphibians and their mechanism.

• Toxicological Research
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• v.26 no.3
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• pp.209-216
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• 2010

Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A. Cytotoxicity and inhibition on differentiation were measured in each cell. Three doses of olaquindox (4, 21 and 100 mgkg), and 0.2 and 75 mg/kg of vitamin A were administered to pregnant rat for 11 days from $6^{th}$ to $16^{th}$ of pregnancy. $IC_{50}$ values of olaquindox for proliferation and differentiation in CNS cell were 22.74 and $28.32\;{\mu}g/ml$ and 79.34 and $23.29\;{\mu}g/ml$ in LB cell and those values of vitamin A were 8.13 and $5.94\;{\mu}g/ml$ in CNS cell and 0.81 and $0.05\;{\mu}g/ml$ in LB cell, respectively. Mean body weights of pregnant rats were decreased at high dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea, and number of implantation were not changed. Resorption and dead fetus were increased at high dose of olaquindox, and relative ovary weight, the number of corpus lutea and implantation, and sex ratio of male to female were not significantly changed in all dose of olaquindox. Mean fetal and placenta weights were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed visceral anomalies at high group. The ossification of sternebrae and metacarpals were significantly (p < 0.01) increased by low and middle dose of olaquindox but it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats treated with vitamin A, the resorption and dead fetus were increased by high dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52 showed external anomaly; bent tail (1), cranioarchschisis (14), exencephaly (14), dome shaped head (22), anophthalmia (15), brcahynathia (10) and others (19). Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone (21/61), defect of palatine bone (52/61) and others (50/61). In summary, we support that vitamin A is strong teratogen based on our micromass and in vivo data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS cell. We provide the in vivo evidence that a high dose of olaquindox could have weak embryotoxic potential in rats.