• Safety and Health at Work
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• v.2 no.3
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• pp.290-300
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• 2011

Objectives: There is limited data regarding the toxicity of methylcyclohexane, despite its wide use in rubber adhesives, paint diluents, and cleansing agents. This study aimed to verify the toxicity and influence on the reproductive system of methylcyclohexane after its repeated injection in Sprague Dawley (SD) rats. Methods: Methylcyclohexane was injected subcutaneously into male and female SD rats once a day, five times a week, for 13 weeks at different doses (0, 10, 100, and 1,000 mg/kg/day) for each group. The toxicity of testing material was verified by observing the change in body and organ weight, hematological change, pathological findings, and effect on the reproductive system at each different concentration. Results: In the 1,000 mg/kg/day group, there were cases of animal deaths. In animals that survived, hematological changes, including a decrease in the red blood cell count, were observed. A considerable weight gain or loss and pathological abnormalities in the liver, kidney, and other organs were found. However, the 10 and 100 mg/kg/day groups did not cause deaths or other specific abnormalities. In terms of reproductive toxicity, there were changes in hormone levels, including a significant decrease in hormones such as estradiol and progesterone (p < 0.001) in male animals. Menstrual cycle change for female animals did not show concentration dependency. Conclusion: When injected repeatedly for 13 weeks, methylcyclohexane proved to be toxic for the liver, heart, and kidney at a high dose. The absolute toxic dose was 1,000 mg/kg/day, while the no observed adverse effect level was less than 100 mg/kg/day. The substance exerted little influence on the reproductive system.

• Development and Reproduction
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• v.19 no.4
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• pp.167-180
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• 2015

Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity.

• Toxicological Research
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• v.17 no.4
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• pp.267-272
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• 2001

This study was carried out to assess the reproductive toxicity of 2-bromopropane (S-BP) using spermatogenesis stage classification and Sertoli cell indices (SCI).Vehicle control olive oil and 2-BP doses of 125, 250 and 500 mg/kg of body weight were injected in the interaperitoneum of 12 weeks male Sprague-Dawley rats for 28 days respectively of SCI on germ cells including the spermatogonia of stages II-III, Ⅵ,Ⅹ, XII, ⅩIII, and spermatocytes of stages VIII (preleptotene), Ⅹ (leptotene), XII (leptotene), V and Ⅵ (pachytene), and the round spermatids of stage Ⅵ. Considering the process of maturation depletion in spermatonesis, spermatogonia may be the primary target cells of 2-BP toxicity.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.333-340
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• 2024

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.

• 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.

• Korean Journal of Pharmacognosy
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• v.40 no.2
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• pp.89-98
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• 2009

The toxicity of aristolochic acid (ArA) has attracted considerable attention since the case of nephropathy regarding diet pill preparations was reported. The present study was performed to determine the reproductive toxicity of ArA in female SD rats. ArA was administered orally to female rats at 2, 8 or 16 mg/kg b.w./day and the females were mated with untreated males and their reproductive status was determined. ArA is well known as PLA2 inhibitor, toxic effects of such a relationship are not yet clear, and in vivo study on this matter are scarce. For this study, ArA was administered to pregnant rats at 10 or 20 mg/kg b.w./day, because premating treatments were not conducted. Administration of 20 mg/kg b.w./day caused infertility or abortion. In ArA-treated groups, PGF2a productions were inhibited and apoptosis were suppressed. Collectively, this study may help to further define the roles of sPLA2 in reproductive organs and to determine the toxic mechanisms of ArA.

• Toxicological Research
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• v.17
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• pp.25-35
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• 2001

In 1990, Tolerable Daily Intake (TDI) of 10 pg TCDD/kg/day for dioxins based on carcinogenicity and reproductive toxicity was determined by WHO/EURO, that resulted in the establishment of TDIs in other countries. In Japan, Ministry of Health and Welfare and Environment Agency, respectively established the TDI of 10 pg TCDD/kg/day and Health Risk Assessment Index of 5 pg TCDD/kg/day in 1996. Accumulation of new scientific data, especially by molecular toxicology since 1990, resulted in the reevaluation of TDI by WHO-ECEH and IPCS in May, 1998. At this meeting, it was stressed that \circled1 toxic effects of dioxin is mediated through Ah-receptor in both animals and humans, \circled2 use of ebody burdeni concept is better than the use of traditional NOAEL/UF approach, \circled3 inclusion of coplanar PCBs in the TDI by the use of new WHO-TEF. LOAELs (0.16~200 ng TCDD/kg/day) obtained from reproductive toxicity and immunotoxicity in rats, and neurobehavioral toxicity and induction of endometriosis in rhesus monkeys are calculated to be the body burden of 10~50 ng TCDD/kg that is 14~37 pg TEQ/kg/day as human daily intake. Finally TDI of 1~4 pg TEQ/kg/day was established by applying the UF of 10. In Japan, reproductive toxicity and immunotoxicity in rats were used to obtain LOAELs (100~200 ng TCDD/kg/day). Finally TDI of 4 pg TEQ/kg/day was established in June 1999 by applying the UF of 10 to human daily intake of 43.6 pg TEQ/kg/day which corresponds to the body burden of 86 ng TCDD/kg.

• YAKHAK HOEJI
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• v.45 no.2
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• pp.190-204
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• 2001

This study was conducted to investigate for its effects on reproductive and developmental toxicity of recombinant human epidermal growth factor (rhEGF) in Sprague-Dawley rats. Male rats were administered rhEGF at doses of 1, 10, 100, and 1000$\mu$g/kg/day, respective1y, by subcutaneous injection from 63 days before and throughout to mating period until the day before sacrifice. Female rats were administered rhEGF at the same doses from 14 days before mating to day 20 of gestation or to day 21 of lactation. We examined the male and female fertility indices and maternal toxicity of F0 parental animals. Also, we examined the external, visceral, or skeletal malformation of fetuses, growth and development, behavior, and/or reproductive performance of F1 animals. At the highest dose (1,000 $\mu$g/kg), the mean body weights of F0 animals were significantly increased in males and females at 3 or 2 weeks after treatment, respective1y. No clinical signs and food intakes were observed at any time during the experimental period by rhEGF treatment. In autopsy examination, the relative and absolute liver weights significantly increased in both sexes of 1,000 $\mu$g/kg. At the highest dose (1,000 $\mu$g/kg), there was a statistically significant increase of pregnancy period and the number of dead fetuses. Moreover, significant increase of mean fetal body weight and decrease of number of live fetuses, which related to the difficult dilivery were observed in highest dose group. In Fl examination, no adverse effects on external, visceral, and skeletal malformation, physical and functional development, behavior or reproductive ability of Fl animals were observed in any group. Also, there was no significant difference between control and treated groups in copulation or fertility indices of Fl animals. These results indicate that rhEGF had no adverse effect on fertility and reproductive ability of Sprague-Dawley rats.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.102-102
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• 2003

Diethylhexyl phthalate (DEHP) was known as endocrine disrupter revealing reproductive / developmental toxicity. For a long time, risk due to DEHP released from PVC medical devices was became an issue for patient receiving blood bag, iv injection solution like saline and Hartman's solution. This study was conducted to suggest permissible intake level (PIL) of DEHP based on reproductive toxicity, to quantify daily intake level of DEHP can be exposed to patient through various medical treatment and to estimate risk values of DEHP released from PVC medical devices.(omitted)

• 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.