• Toxicological Research
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• v.16 no.3
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• pp.229-238
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• 2000

The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.22 no.1
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• pp.73-81
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• 2012

Object: The aim of this study is to suggest a list of priority chemicals for the Hazard & Risk Evaluation of Chemicals (HREC) controlled by the Industrial Safety and Health Act (ISHA). Method: Screening assessment was done for 642 chemicals whose exposure threshold limit values were set by the Ministry of Employment and Labor (MOEL). Hazard data were collected from Korea Occupational Safety & Health Agency (KOSHA) and/or other toxicity database. Exposure data were obtained from KOSHA internal database. The hazard and exposure scores of chemicals were listed by order of priority in accordance with GHS classification and exposure index data. Result: From the result of screening risk assessment for 642 chemicals, we extracted a list of 13 priority chemicals for HREC performed by the ISHA. A priority list of 27 chemicals which have carcinogen, mutagen and/or reproductive toxicity but not controlled by the ISHA was suggested for additional evaluation as "chemicals for special management".

• Toxicological Research
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• v.17 no.2
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• pp.97-106
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• 2001

Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that the consumption of food treated with EO might cause harmful effects in human. Since, in Korea the use of EO gas for food treatment was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to investigate the effects of irradiated ginseng on fertility, and reproductive and developmental toxicity. Either EO gas fumigated or gamma-irradiated ginseng was administered to male rats by oral gavage for 63 days during the premating period. Female rats were administered from 14 days before mating to day 20 of gestation or to day 21 of lactation. The exposure amount of irradiation used was 5, 10 and 30 kGy, respectively. There were no treatment related changes of darns in clinical signs, and parturition. No treatment related changes in food consumption, body/organ weights, male/female reproductive and fertility performances were observed. F1 fetuses showed no external abnormality. Reflex/sensory junctions, physical/behavioral development, and reproductive performance of F1 rats were not adversary affected. The results of this study show that gamma-irradiated ginseng, up to 30 kGy, has no adverse effects on the fertility, reproduction and development in Wistar rats.

• Toxicological Research
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• v.14 no.2
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• pp.193-203
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• 1998

The toxicity of DA-125. a new anthracycline anticancer agent, on the male reproductive system was studied in Sprague-Dawley rats. Forty male rats were rando$m\ell$y assigned to Jour groups with ten rats in each group and given single intraveneous doses of DA-125 at dose levels of 0. 12.5. 25. and 50 mg/kg body weight. On day 56 after treatment the animals were allowed to mate. and their male reproductive Junctions and organs were examined in detail. Copulated females were sacrificed on day 20 of gestation for examination of embryo-fetal development. One out of ten rats in the 50 mg/kg group died on day 12 after treatment. Clinical signs such as emaciation. sedation, anorexia. swelling. dark material around eye. alopecia. and diarrhea were observed in the 25 and/or 50 mg/kg groups. Reduction in the body weight gain. decrease in the absolute weights of testes. epididymis and seminal vesicles. and/or decrease in the number of testicular sperm heads were also found. Although histopathological changes such as atrophy of seminiferous tubules. loss or decrease of spermatogenic cells. exfoliation of spermatogenic cells. vacuolization of Sertoli cells. decrease of sperm. and/or increase of necrotic spermatogenic cells in epididymal ducts were observed. no adverse effects on the motility and morphology of epididymal sperm. copulation index. fertility index. and embryo-fetal development were detected in the 25 and 50 mg/kg groups. There were no evidences of male reproductive toxicity in the 12.5 mg/kg group. These results show that single intravenouse doses of DA-125 produce significant dose-related testicular atrophy. histopathological changes. and oligozoospermia in rats and $LD_{10}$ for DA-125 appears to be 50 mg/kg body weight.

• Toxicological Research
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• v.18 no.1
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• pp.1-11
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• 2002

3-Monochloro-1,2-propanediol(3-MCPD) is currently being a matter of concern because of its toxicity. 3-MCPD produced during the acid hydrolysis of soybean products has been reported to be mutagenic, neurotoxic, nephrotoxic and spermatotoxic. Howerer, the carcinogenicity of 3-MCPD is a controversial issue over the past several decades. 3-MCPD characteristically showed a variety of toxicities in reproductive system such as, decrease in sperm number and sperm motility, infertility, loss of sperm function, and weight decrease in ovary. Due to the toxicity of 3-MCPD, exposure to 3-MCPD has been proposed to be reduced to as low a level as technologically feasible. 3-MCPD can be detected in soy sauce or non-soy sauce products. The legal limit for 3-MCPD this year has been suggested to be 20 ppb（$\mu\textrm{g}$/kg）in the European Community. In Korea, the permissible level of 3-MCPD is expected to be 0.3 ppm. In this study, 3-MCPD was toxicologically evaluated in terms of risk assessment in humans.

• Toxicological Research
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• v.21 no.4
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• pp.271-278
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• 2005

Reproductive and developmental toxicology is concerned with various physical or chemical agents interfering with fertility in both gender or normal growth of offsprings. Reproductive and developmental toxicology is rather a complex science, with many fields, i.e., various endpoints are involved and many different mechanisms of action. For that reason, diverse aspects must be considered when attempting to assess possible adverse health effects in the area of reproductive and developmental toxicology. The thalidomide tragedy made it clear to regulatory authorities around the world that systematic, comprehensive evaluation of the reproductive cycle was needed to adequately evaluate the potential of medicinal drugs to impair the process of reproduction or the development of embryos, fetuses, and children. International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) and U.S. Food and Drug Administration (FDA) developed a guideline to assess the reproductive and developmental toxicity. Also these guidelines have since been applied to the detection and regulation of environmental toxicants, food additives, and so on. Although it was hoped that testing procedures of guideline would be updated constantly to reflect the current state of the science in reproductive and developmental toxicology, it was not until this decade that regulatory guidelines and testing methods have been altered in a significant way. In this paper, we would like to present the recommended approaches and recent trends for improvement of testing guidelines or experimental methods in reproductive and developmental toxicology.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.77-81
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• 2001

Kamijadowhan (KMD), an oriental herbal medicine used for anti-angiogenic effect, was extracted with 80% ethanol from mixture of source materials and lyophilized. KMD was orally administered to plugpositive pregnant rats from gestational days 12 to 20, dividing into three groups including vehicle-treated control, 0.5 g/kg or 3 g/kg KMD-treated groups. Dam weight during gestation and post-gestation, weight of pre- and post-weaning offsprings in male and female, and reproductive and developmental endpoints including incisor eruption, eye opening and testes descent were measured. No significant alterations in development of physical landmarks in offspring, maternal weight gain during gestation and post-gestation, and offspring weight were observed in KMD-treated group. The measurement of organ weight at post-gestational days 21 was not changed in dams. In 0.5 g/kg KMD-treated rats, kidney weights in male and female offsprings were significantly increased, and the body weight in male offspring was also increased. Liver and brain weights were not changed. Taken together, these data suggest that KMD may not significantly cross the placenta and produce no reproductive and developmental toxicity at maternally non-toxic dosages.

• Toxicological Research
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• v.26 no.1
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• pp.67-74
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• 2010

The present study was conducted to obtain information on the effects of amitraz on reproductive and developmental parameters in rats. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and up to lactational day 4. During the study period, clinical signs, body weights, food intake, organ weights, reproductive and littering findings, necropsy findings, sperm parameters, and histopathology were examined. At 360 ppm, decreases in the body weight gain, food consumption, and the number of live pups and an increase in the post-implantation loss were observed. In addition, decreases in the seminal vesicle weight and sperm motility were found in males. At 120 ppm, a decrease in the food consumption was found transiently in both males and females, but no reproductive and developmental toxicity was observed in both sexes. There were no signs of either general or reproductive and developmental toxicity in the 40 ppm group. Based on these results, it was concluded that the repeated oral administration of amitraz to rats resulted in a decrease in the food consumption at 120 ppm and decreases in the seminal vesicle weight, sperm motility, and the number of live pups and an increase in the post-implantation loss at 360 ppm in rats. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz for general and reproduction/developmental toxicity was believed to be 120 ppm, and the no-observed-effect level (NOEL) of amitraz was believed to be 40 ppm in rats.

• Toxicological Research
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• v.12 no.1
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• pp.93-99
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• 1996

The effect of KTC-1, a new semisynthetic rifamycin antituberculous drug, on general toxicity, reproductive capability and fetal development was investigated in Sprague-Dawley rats. Male rats were administered KTC-1 with mashed feed from 63 days before mating to the end of mating period, and female rats were given from 14 days before mating to day 7 of gestation at dose levels of 0, 375, 750, and 1,500 ppm. The females were sacrificed on day 21 of gestation for examination of their fetuses. At 1,500 ppm, a reduction in body weight gain and testis atrophy were observed in male rats. Histological examination revealed testicular atrophy, absence or decrease of germinal cells, and vacuolization of Sertoli cells in testis. A reduction in body weight gain, a decrease in food consumption were found in female rats. In addition, decreases in the number of corpora lutea, iraplantations, and the litter size of live fetuses were seen. Mating, fertility, and pregnancy performances were also affected. There were no external abnormalities observed by examination of fetuses. At 750 ppm, a reduction in the body weight gain of male and female rats and decreases in the number of implantations and litter size were found. At 375 ppm, no treatment-related effects were observed. The results suggest that the no-effect dose levels (NOELs) of KTC-1 are 375 ppm for males and females on general toxicity, 750 ppm for males and females on reproductive capability, and 375 ppm for fetuses on embryonic development.

• Toxicological Research
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• v.23 no.4
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• pp.391-403
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• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.