• Korean Journal of Veterinary Research
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• v.40 no.2
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• pp.361-371
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• 2000

It has been recently reported that 2-bromopropane (2-BP) induces male reproductive toxicity in both human and experimental animals. However, delayed effects of 2-BP on male reproductive system have not been investigated in detail. The present study was conducted to investigate the testicular toxicity of 2-BP and to determine the recovery of normal spermatogenesis in Sprague-Dawley rats. Male rats aged 5 weeks were administered 1,000mg/kg 2-BP by gavage daily for 4 weeks and sacrificed sequentially at 1, 2, 3, 4 and 12 weeks after initiation of 2-BP treatment. Testicular toxicity was evaluated qualitatively by histopathological examinations and quantitatively by reproductive organ weights, spermatid head count, and repopulation index. In the 2-BP treated rats, the body weights was significantly suppressed and the weights of testes and epididymides were also decreased in a time-dependent manner. On histopathological examination, spermatogonia in stages I-VI and preleptotene and leptotene spermatocytes in stages VII-IX were strongly depleted at 1 week of dosing. Spermatogonia were depleted extensively in all spermatogenic stages at 2 weeks. Continuing with the evolution of spermatogenic cycle, zygotene spermatocytes, pachytene spermatocytes, and round spermatids were sequentially depleted at 2, 3, and 4 weeks of dosing due to the depletion of their precursor cells. Vacuolization of Sertoli cells and spermatid retention were also observed at all time points, suggesting that 2-BP induced Sertoli cell dysfunction. At 12 weeks, after 8 weeks recovery, most of the tubules appeared severely atrophic and were lined by Sertoli cells only. Leydig cell hyperplasia in the interstitial tissue was also found. In addition, dramatic reductions in the number of spermatid heads and repopulation index were observed, indicating that 2-BP-induced testicular injury is irreversible. These results indicate that 4 weeks repeated-dose of 1,000mg/kg 2-BP results in a progressive germ cell loss due to the depletion of spermatogonia followed by long-term testicular atrophy in SD rats.

• Korean Journal of Environmental Biology
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• v.27 no.4
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• pp.323-333
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• 2009

Parabens are alkyl esters of p-hydroxybenzoic acid, which are widely used in foods, cosmetics, and pharmaceutic products as preservatives. Absorbed parabens are metabolized fastly and excreted. Actually human body is exposed to complex mixture of parabens. Safety assessment at various toxicological end points revealed parabens have a little acute, subacute and chronic toxicities. Some reports have argued that as parabens have estrogenic activity, they are associated with the incidence of breast cancer through dermal absorption by cosmetics. There is an inference that antiandrogenic activity of parabens may give rise to a lesion of male reproductive system, but also there is an contrary. At cellular level, parabens may inhibit mitochondrial function of sperms and androgen production in testis, but also there is an contrary. Parabens seem to have little or no toxicity in embryonic development. Parabens can cause hemolysis, membrane permeability change in mitochondria and apoptosis, suggesting cellular toxicity of parabens. Parabens evoked endocrine disruption in several fish species and have toxic effect on small invertebrates and microbes. Therefore, the toxicity of parabens should be considered as a potentially toxic chemical in the freshwater environment. In conclusion, though parabens may be considered as a low toxic chemical, more definite data are required concerning the endocrine disrupting effect of parabens on human body and aquatic animals according to route and term of exposure as well as the residual concentration of parabens.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.102-113
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• 2006

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

• The Korean Journal of Pesticide Science
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• v.14 no.4
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• pp.490-498
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• 2010

Isotianil is a fungicide which has prevention effects against rice blast disease. In order to register this new pesticide, the series of toxicity data on animal testing were reviewed to evaluate its hazards to consumers and to determine its acceptable daily intake. Isotianil was almost excreted by urine and feces. It has low acute oral toxicity while has no skin toxicity and ocular irritation. Its skin sensitization was evaluated as slight. Genotoxicity of parent compound and metabolite was negligible. Chronic toxicity tests on rats and dogs showed changes of hematology, clinical biochemistry and liver weight. It had no reproductive and teratogenic effects. The estimation of Acceptable Daily Intake(ADI) is based on the lowest no-observed adverse effect level (NOAEL). The lowest NOAEL of 2.83 mg/kg bw/day was found in the twelve-months rats study. The NOAEL was based on increased liver weight and treatment-related effect on clinica chemistry finding at the nest higher dose level of 2.83 mg/kg bw/day. Therefore, it is considered appropriated to apply an uncertainty factor of 100 to the NOAEL 2.83 mg/kg bw/day from the rat study, resulting in an ADI of 0.028 mg/kg bw/day.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.442-448
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• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.

• Korean Journal of Acupuncture
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• v.34 no.4
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• pp.241-250
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• 2017

Objectives : This study was performed to examine the toxicity of Aconitum ciliare Decaisne pharmacopuncture(ADP). Methods : The toxicity was evaluated for lethal dose for 50 percent kill(LD50), single dose and repeated dose for 4 weeks. Toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test were observed for 4 weeks. Dose of 300, 600, 1,200, 2,400, 3,600, 4,800, 6,000, 7,200 mg/kg in the LD50 experiment, 300, 600, 1,200 mg/kg/day in the single experiment, 150, 300, 600 mg/kg/day in 4 weeks experiments were injected into BALB/c mice. The ADP was injected into ST36 of the right leg. Normal saline solution of same volume was used for control group. In 24 hours after the last treatment, blood samples were taken after anesthesia by inhalation of ethyl ether. After that, the BALB/c mice were euthanized. Their heart, lungs, kidneys, liver and reproductive organs were removed and weighed. Histopathological evaluation was also performed. Results : ADP's LD50 was measured at 6,000 mg/kg. In both single and repeated dose toxicity test, no BALB/c mouse died during the experiments. ADP treatment for 4 weeks did not show any significant changes in toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test. Conclusions : As a result, ADP's LD50 was 6,000 mg/kg and repeated dose at a concentration of 600 mg/kg or less is considered to be not harmful for clinical treatment.

• Toxicological Research
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• v.11 no.1
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• pp.69-75
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• 1995

The present study was carried out to establish several spermatotoxicity test methods. For this purpose we investigated following parameters in the fertility study of DA-125, a new anticancer agent, in rats: testicular spermatid counts, epididymal sperm counts, daily sperm production rate, sperm morphology, and serum testosterone concentration. Motility and velocity of sperms were also measured using non-treated rats. At 0.3 mg DA-125/kg, spermatids per 1g testis and daily sperm production rate per 1g testis were significantly decreased, when compared with those of control group. Several types of abnormal sperms, such as no head, pin head, double head, hook at wrong angle, no tail, and small sperm, were found in both treated and control groups at a low frequency. Serum testosterone concentration at 0.3 mg DA-125/kg was close to the control value. Sperm motility and velocity measured with non-treated rats were in a good agreement with the results of other investigators. In our study established spermatotoxicity test methods can be used as a tool not only for the close examination of the cause of drug- or chemical-induced infertility, but also for the effective evaluation of reproductive toxicity.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.05a
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• pp.102-102
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• 2003

• Reproductive and Developmental Biology
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• v.34 no.1
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• pp.15-19
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• 2010

Oocyte enucleation is essential for somatic cell nuclear transfer (SCNT) in the production of cloned animals or embryonic stem cells from adult somatic cells. Most studies of oocyte enucleation have been performed using micromanipulator-based techniques, which are technically demanding, time-consuming, and expensive. Several recent studies have used chemical-induced oocyte enucleation; however, each has been plagued by low efficiency and toxicity. In this study, I found that the co-treatment of murine oocytes with demecolcine and BMI-1026, a potent cdk1 inhibitor, resulted in a high enucleation rate (97%). This method is entirely independent of a micromanipulator and is suitable for the large-scale production of enucleated oocytes. This new method of enucleation will be useful in SCNT and in the development of handmade cloning techniques.

• Environmental Analysis Health and Toxicology
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• v.23 no.1
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• pp.63-65
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• 2008

The tissue distribution of $TiO_2$, nanopaprticles was investigated in mice after oral administration, and skin treatment. Male mice were treated with the dose of 5 g/kg of $TiO_2$ for three consecutive days and sacrificed at 24 hours after the last administration. As results, the orally administered $TiO_2$ nanoparticels were shown to be distributed in the testis, lung, and brain at 24 hours after the last treatment. Kidney does not seem to be the main target of $TiO_2$ nanoparticle distribution. It means that $TiO_2$ nanoparticles (17 nm) are easily absorbed through entero-gastric system and may cause toxicity in brain, lung, and reproductive organs. The distribution of skin treatment showed the same pattern like oral administration.