• 한국환경성돌연변이발암원학회지
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• 제16권1호
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• pp.30-34
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• 1996

This study was performed to examine the availability of using medaka (Oryzias latipes) in teratological test. Medaka embryos were collected within 2 hours post-fertilization and cultured in petri dishes containing buffered saline until hatching. The embryos were treated with 0.56 mg/l chlorpyrifos-methyl and 10 mM methyl methanesulfonate at 20 stages (about 35 hours post-fertilization). Eleven developmental features were selected and observed from 33 stages (about 9 days post-fertilization). Scoring system was developed and applicated for the measurement of potential teratological effects by the test compound. Chlorpyrifos-methyl did not induce teratological effect in medaka embryos. However, we found teratological test using medaka embryo reduced the cost, labors, period and space of experiment significantly compared with teratological study using rodents. Above findings strongly suggest that medaka embryo can be used as a lab animal model for teratogenicity test instead of rodents.

• Asian-Australasian Journal of Animal Sciences
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• 제24권8호
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• pp.1053-1059
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• 2011

The objective of this study was to assess the teratogenic and embryotoxic effects of clomiphene citrate in mice. The pregnant mice were administered a single dose of clomiphene citrate at different concentrations i.e 1.0, 2.0, 4.0 and 6.0 ${\mu}g/g$ BW on day 8 of gestation. Fetuses recovered on day 18 of gestation were analyzed on morphological, morphometric and histological basis. Morphological observations showed defects like open eyelids, anophthalmia, fore and hindlimb micromelia, meromelia, amelia, sacral hygroma, hydrocephaly, hemorrhagic spots, kyphosis and clubbed feet. Morphometric analysis indicated a significant (p<0.001) reduction in fetal body weight, crown rump length, head circumference, eye circumference, forelimb and hindlimb lengths and tail size against controls. The histological observations showed brain defects like hydrocephaly, enlarged ventricles and undifferentiated neuroglial cells in cerebellum. Cleft palate, underdeveloped pharynx and atrophy of jaw muscles were the common anatomical defects of pharyngeal region. It is concluded that the concentrations of clomiphene citrate used during the present study proved teratogenic in mice fetuses.

• Toxicological Research
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• 제23권2호
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• pp.151-158
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• 2007

tert-Butyl acetate is an organic solvent used for coatings, industrial cleaning, and surface treatment applications. This study investigated the potential adverse effects of tert-butyl acetate on pregnant dams and embryo-fetal development after maternal exposure on gestational days 6 through 19 in rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 500, 1,000, 1,500, and 2,000 mg/kg/day. All dams were subjected to a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 2,000 mg/kg, treatment-related clinical signs, including piloerection, abnormal gait, decreased locomotor activity, loss of fur, reddish tear, anorexia, nasal discharge, vocalization and coma, were observed in a dose-dependent manner. All dams died between the 2nd day and 5th day of treatment due to a severe systemic toxicity. At 1,500 mg/kg, minimal maternal toxicity including an increase in the incidence of decreased locomotor activity and loss of fur, and an increase in the weights of adrenal glands and liver was observed. On the contrary, no significant adverse effect on the embryo-fetal development was detected. There were no adverse effects on either pregnant dams or embryo-fetal development at <1,000 mg/kg. These results show that a 14-day repeated oral dose of tert-butyl acetate in rats caused a minimal maternal toxicity including increases in the incidence of clinical signs and the weights of adrenal glands and liver, but no embryotoxicity and teratogenicity at 1,500 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of tert-butyl acetate is estimated to be 1,000 mg/kg per day for dams and 1,500 mg/kg per day for embryo-fetal development.

• Toxicological Research
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• 제24권4호
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• pp.263-271
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• 2008

Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.

• Toxicological Research
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• 제3권1호
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• pp.45-53
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• 1987

A teratogenicity study was carried out on Sprague-Dawley rats which have been given the intravenously or intraperitonealy injections of rHuIFN-${\alpha}$A, an available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the off springs was observed. No changes were observed in all aspects of parameters between the treated and the control dams. The incidence of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. The rHuIFN-${\alpha}A$ caused no effects on parturition, lactation, and postnatal growth.

• 한국환경성돌연변이발암원학회지
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• 제21권2호
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• pp.113-117
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• 2001

The screening of various molecular descriptors for predicting carcinogenic, mutagenic and teratogenic activities of chlorinated aliphatic compounds as drinking water disinfection byproducts (DBPs) has been investigated for the application of quantitative structure-activity relationships (QSAR). The present work embodies the study of relationship between molecular descriptors and toxicity parameters of the genotoxicity endpoints for the screening of relevant molecular descriptors. The toxicity Indices for 29 compounds constituting the testing set were computed by the PASS program and active values were chosen. We investigate feasibility of screening descriptors and of their applications among different genotoxic endpoints. The correlation to teratogenicity of all 29 compounds was significantly improved when the same analysis was done with 20 alkanes only without alkene compounds. The HOMO (highest occupied molecular orbital) energy and number of Cl parameters were dominantly contributed.

• Toxicological Research
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• 제35권2호
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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.

• 약학회지
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• 제55권2호
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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.

• 한국환경생태학회지
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• 제33권2호
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• pp.178-186
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• 2019

국내에 서식중인 청개구리의 배아를 활용하여 농약류 3종의 독성평가를 위해 FETAX(Frog Embryo Teratogenesis Assay-Xenopus) 기법에 따라 청개구리(Hyla japonica)의 배아를 배양하면서 Benomyl(살균제), Carbofuran(살충제), Thiobencarb(제초제)의 효과를 probit 분석법으로 조사하였다. 그 결과, Benomyl, Carbofuran, Thiobencarb의 농도에 의존하여 유생의 체장 길이는 감소하고 치사율과 기형율은 증가하였다. Benomyl, Carbofuran, Thiobencarb의 teratogenic concentration($EC_{50}$)은 각각 1.00, 0.58, 4.75mg/L을 나타내어 Carbofuran이 기형유발에 가장 민감하게 반응하였으며, embryo lethal concentrations($LC_{50}$)은 7.04, 28.71, 16.12mg/L을 나타내어 Benomyl이 가장 낮은 농도에서 배아를 치사하는 것으로 나타났다. Teratogenic index($TI=LC_{50}/EC_{50}$)는 Benomyl 7.04, Carbofuran 49.50, Thiobencarb 3.39를 나타내어 TI값이 모두 기형유발물질로 판단하는 기준인 1.5 이상을 나타내어 시험에 사용된 농약류 3종은 최기형성 물질로 판단되며 Carbofuran이 가장 강력한 최기형성물질로 작용함을 알 수 있었다.

• 대한한의학방제학회지
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• 제31권1호
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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.