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ZnSe quantum-dots were synthesized in an aqueous system and UV irradiation was introduced as a post-treatment process. The synthesis temperature was varied from 25 oC to 90 oC, and the surface of the nano powder was stabilized using different ligands such as glutathione (GSH), 3-mercaptopropionic acid (MPA) and thioglycolic acid (TGA). Then, the effect of UV irradiation on the structure and the absorption/ emission properties of the nano powder were investigated. As the UV light was irradiated, the PL intensity of the quantum dots increased. UV irradiation for 16 h increased the PL intensity of the synthesized quantum dots at room temperature to the level of those at 90 oC. Particle aggregation was not found with UV irradiation of at least 24 h. XRD patterns confirmed that the UV irradiation released sulfur from the GSH, inducing the formation of the ZnSe/ZnS composite-typed nano powders. The luminescence characteristics of the GSH or TGA-added quantum dots were enhanced by UV irradiation regardless of temperature, while MPA-added quantum dots were not significantly affected by UV irradiation. The post-treatment process with UV irradiation showed the possibility that even ZnSe quantum dots, which are synthesized at low temperature and have low luminescence intensity, can have luminescence characteristics comparable to those of high-temperature synthesis.

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a phenolic compound widely used in pharmaceutics and nutraceutics. Although resveratrol is produced by some plant species, including grapes, peanuts, and berries, the content of resveratrol and its derivatives are very low. Therefore, an alternative biosynthetic method using microorganisms, such asEscherichia coli, has been developed over the past two decades. In the present study, a resveratrol-over-producingE. colistrain was developed using three strategies. First, we increased the synthesis ofp-coumaric acid, a precursor of resveratrol, by manipulating genes in the shikimate pathway ofE. coli. Second, three genes involved in resveratrol biosynthesis, such as tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), and stilbene synthase (STS), were cloned from diverse sources, such as plants and microorganisms, and the best combination was selected to maximize resveratrol production inE. coli. Finally, culture conditions, such as cell concentration, culture temperature, and carbon sources, were established for optimal resveratrol production. Through these strategies, approximately 80.4 mg/L of resveratrol was biosynthesized after 48 h of culture using glycerol as a carbon source.

Antibody&ndash, drug conjugate (ADC) linkers play an important role in determining the safety and efficacy of ADC. The Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker is a newly developed linker in the form of a di-aryl sulfate structure consisting of phenolic payload and self-immolative group (SIG). In this study, using two bioanalytical approaches (namely &ldquo, bottom-up&rdquo, and &ldquo, middle-up&rdquo, approaches) via the liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method, in vitro and in vivo linker stability experiments were conducted for the OHPAS linker. For comparison, the valine-citrulline-p-aminobenzyloxycarbonyl (VC-PABC) linker was also evaluated under the same experimental conditions. In addition, the catabolite identification experiments at the subunit intact protein level were simultaneously performed to evaluate the catabolic fate of ADCs. As a result, the OHPAS linker was stable in the in vitro mouse/human plasma as well as in vivo pharmacokinetic studies in mice, whereas the VC-PABC linker was relatively unstable in mice in vitro and in vivo. This is because the VC-PABC linker was sensitive to a hydrolytic enzyme called carboxylesterase 1c (Ces1c) in mouse plasma. In conclusion, the OHPAS linker appears to be a good linker for ADC, and further experiments would be warranted to demonstrate the efficacy and toxicity related to the OHPAS linker.

Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. A quadratic regression (weighted 1/concentration2), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the in vitro and in vivo data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.

5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c) pyrimidine (SCH 58261) is one of the new chemical entities that has been developed as an adenosine A2A receptor antagonist. Although SCH 58261 has been reported to be beneficial, there is little information about SCH 58261 from a drug metabolism or pharmacokinetics perspective. This study describes the metabolism and pharmacokinetic properties of SCH 58261 in order to understand its behaviors in vivo. Rats were used as the in vivo model species. First, an LC&ndash, MS/MS method was developed for the determination of SCH 58261 in rat plasma. A GastroPlus&trade, simulation, in vitro microsomal metabolic stability, and bile duct-cannulated studies were also performed to understand its pharmacokinetic profile. The parameter sensitivity analysis of GastroPlus&trade, was used to examine the factors that influence exposure when the drug is orally administered. The factors are as follows: permeability, systemic clearance, renal clearance, and liver first-pass effect. In vitro microsomal metabolic stability indicates how much the drug is metabolized. The extrapolated hepatic clearance value of SCH 58261 was 39.97 mL/min/kg, indicating that the drug is greatly affected by hepatic metabolism. In vitro microsomal metabolite identification studies revealed that metabolites produce oxidized and ketone-formed metabolites via metabolic enzymes in the liver. The bile duct-cannulated rat study, after oral administration of SCH 58261, showed that a significant amount of the drug was excreted in feces. These results imply that the drug is not absorbed well in the body after oral administration. Taken together, SCH 58261 showed quite a low bioavailability when administered orally and this was likely due to significantly limited absorption, as well as high metabolism in vivo.

Parkinson&rsquo, s disease is one of the most common neurodegenerative diseases. Adenosine regulates the response to other neurotransmitters in the brain regions related to motor function. In the several subtypes of adenosine receptors, especially, adenosine 2A receptors (A2ARs) are involved in neurodegenerative conditions. ZM241385 is one of the selective non-xanthine A2AR antagonists with high affinity in the nanomolar range. This study describes the in vitro and in vivo pharmacokinetic properties of ZM241385 in rats. A liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qToF MS) method was developed for the determination of ZM241385 in rat plasma. In vivo IV administration studies showed that ZM241385 was rapidly eliminated in rats. However, the result of in vitro metabolic stability studies showed that ZM241385 had moderate clearance, suggesting that there is an extra clearance pathway in addition to hepatic clearance. In addition, in vivo PO administration studies demonstrated that ZM241385 had low exposure in rats. The results of semi-mass balance studies and the in silico PBPK modeling studies suggested that the low bioavailability of ZM241385 after oral administration in rats was due to the metabolism and by liver, kidney, and gut.

One of the main factors restricting production of triploid seedless watermelon is poor germination due to weak embryos, thick seed coats, and larger air spaces. This study was carried out to investigate the priming effects of different concentrations of chemicals, including hydrogen peroxide (H₂O₂), fusicoccin, and gibberellic acid (GA) on germination and seedling uniformity of triploid watermelon (Citrullus lanatus). Three commercial triploid cultivars, Seedless Plus, Sinus, and Sizero, were pretreated with water and different levels of H₂O₂ (2 and 4%), fusicoccin (FC: 1, 5, and 10 μM), and GA (1, 5, and 10 μM). The present findings helped to find optimal priming conditions for improving germination of triploid watermelon. Treatment with 5 μM GA and hydropriming helped to break seed dormancy, enhancing the final germination percentages in all triploid cultivars and increasing the germination index in Sizero. These seed-priming treatments could be used on large scale for industrial applications. Moreover, hydropriming provides a simple, effective, and costless method to improve seed germination and seedling vigor of Sinus and Sizero varieties.

Super typhoons develop as a result of meteorological changes. In 2012, Typhoons Bolaven and Denba reached Korea. The maximum instantaneous wind speed of the typhoons reached 60 m/sec. Harbor structures including sofa block sustained damage and loss by the abnormally high waves. In Korea, tetrapod blocks were installed the most for wave dissipating. Nevertheless, a structural evaluation of the tetrapod block has not been performed. This study examined the structural mechanism and weakness part of the tetrapod block under a range of boundary conditions. The block has weakness against a tensile force because it is plain concrete. The joint part of the legs is the most vulnerable to tensile stress. The weakest part can be reduced if the joint part is reinforced as a hunch.

The socio-network activities for regional governments, agricultural research institutes, developing agencies and policy makers of any countries are very crucial and important to take into account the root cause of current problems faced by farmers. The survey was conducted in South Korea during the period January, 2008 to August, 2012 in order to shed light on prevalence of different diseases on watermelon in different regions and to better understand farmers’ knowledge and perceptions for following watemelon’s growing procedures and practices. A total of 590 cases were reported on 573 watermelon growers with highest 87.1% in Jeonbuk, 4.7% in Jeonnam, and 8.2% in other regions such as Gyeongbuk, Gyeongnam, Chungnam, Gwangju, Gyeonggi, Daegu, Gangwon, Changwon and Seoul. The maximum percentages of cases recorded were related to diseases and insect pest (38.6%) followed by physiological disorder (29.7%), cultural practices (18.8%), soil and fertilizer (9.0%), herbicide (2.9%) and others (1.0%). It was observed that the manifestation aspects of the diseases were changed due to increasing in proportion of ‘in-facility’ cultivation to 12,995 ha compared to ‘open-field’ cultivation (2,722 ha). The present survey revealed the necessity to reduce the damages incurred at watermelon farms as soon as possible through the breeding program to develop resistant cultivar, use of pathogen-free propagating plants, and efficient prevention of pathogen by regular monitoring of watermelon plants at farms.

The present experiment was aimed to study the effect of imposing modulated temperature treatments 14 °C and 18 °C, around the fruiting region of watermelon plants, and to estimate the economic feasibility of the temperature treatments based on energy consumption for heating. Watermelon cultivar 'Sambok-gul' was selected and sown on perlite beds in a plastic house under controlled conditions at Watermelon Farm, Jeongeup-Jeonbuk, longitude 35° 31' 47.51N, 126° 48'48.84E, altitude 37 m during the early spring season (2010-2011). The findings revealed that the temperature treatment at 18 °C caused significant increase in weight (2.0 kg plant(-1)), fruit weight (8.3 kg plant(-1)), soluble solid content (11.5 %), and fruit set rate (96.5 %) at harvest stage. Higher contents of Ca(2+) and Mg(2+) ions were observed in the 1st upper leaf of the fruit set node (79.3 mg L(-1)) and the 1st lower leaf of the fruit set node (12.0 mg L(-1)), respectively at 14 °C. The power consumption and extra costs of the temperature treatment 18 °C were suggested as affordable and in range of a farmer's budget (41.14 USD/22 days). Hence, it was concluded that modulating temperature treatments could be utilized successfully to optimize the temperature range for enhancing the fruit yield and quality in the winter watermelon crops.

To screen a suitable method for inducing tetraploid with high frequency, five diploid inbred lines of watermelon, WC-8C-2C, WD-2-6K, GW11, GW7, and GW2 were selected. The efficiency of chromosome doubling with three methods direct seed (DS), shoot apex (SA), and inverted hypocotyl (IH) were tested by applying two different concentrations (0.1% and 0.2%) of antimitotic agent, colchicine, during the period January, 2010 to August, 2011 at Watermelon Experiment Station, Daesan, Gochang, Jeonbuk, South Korea. Mean chloroplast counts were 12 and 19 in diploid and tetraploid, respectively. The highest rate of efficiency of generating tetraploids (29.5%) was recorded in 0.2% IH method and considered as s best method. A total of 71 new tetraploids were generated successfully using present methods and techniques. WC-8C-2C and GW7 produced maximum number of tetraploids.

Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose–response relationship of DPH. This study investigated the dose–response effects of DPH on pregnant dams and embryo-fetal development as well as the relationship between maternal and developmental toxicity. DPH was orally administered to pregnant rats from gestational days 6 through 15 at 0, 50, 150, and 300 mg/kg/day. At 300 mg/kg, maternal toxicity including increased clinical signs, suppressed body weight, decreased food intake, and increased weights of adrenal glands, liver, kidneys, and brain were observed in dams. Developmental toxicity, including a decrease in fetal and placental weights, increased incidence of morphological alterations, and a delay in fetal ossification delay also occurred. At 150 mg/kg, maternal toxicity manifested as an increased incidence of clinical signs, reduced body weight gain and food intake, and increased weights of adrenal glands and brain. Only minimal developmental toxicity, including decreased placental weight and an increased incidence of visceral and skeletal variations, was observed. No treatment-related maternal or developmental effects were observed at 50 mg/kg. These results show that DPH is minimally embryotoxic at a minimal maternotoxic dose (150 mg/kg/day) but is embryotoxic and teratogenic at an overt maternotoxic dose (300 mg/kg/day). Under these experimental conditions, the no-observedadverse-effect level of DPH for pregnant dams and embryo-fetal development is considered to be 50 mg/kg/day. These data indicate that DPH is not a selective developmental toxicant in the rat. Birth Defects Res (Part B) 95:337–345, 2012. C � 2012 Wiley Periodicals, Inc.

This study investigated the protective effects of pine bark extract (Pycnogenol®, PYC) against cyclophosphamide (CP)-induced developmental toxicity in rats. A total of 44 mated females were randomly assigned to the following four experimental groups: (1) vehicle control, (2) CP, (3) CP&PYC, or (4) PYC. All dams were subjected to a Caesarean section on day 20 of gestation, and fetuses were examined for morphological abnormalities. Oxidative stress analysis was performed on maternal hepatic tissues. CP treatment caused decreased fetal and placental weights and increased embryonic resorptions and fetal malformations. In addition, an increased malondialdehyde (MDA) concentration and decreased reduced glutathione (GSH) content and catalase activity were observed in the hepatic tissues. On the contrary, PYC treatment during pregnancy significantly ameliorated the CP-induced embryo-fetal developmental toxicity in rats. Moreover, MDA and GSH concentrations and catalase activity in hepatic tissues were not affected when PYC was administered in conjunction with CP. These results suggest that repeated administration of PYC has beneficial effects against CP-induced embryo-fetal developmental toxicity in rats, and that the protective effects of PYC may be due to both inhibition of lipid peroxidation and increased antioxidant activity.

There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo-fetal development in Sprague-Dawley rats following maternal exposure on gestational days (GD) 6-20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg⁻¹ per day (n = 8-10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg⁻¹ per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment-related maternal or developmental effects were observed at doses ≤ 400 mg kg⁻¹ per day. These results show that 15-day repeated oral dosing of melamine is embryo-/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no-observed-adverse-effect level of melamine for pregnant dams and embryo-fetal development is considered to be 400 mg kg⁻¹ per day.

This study evaluated the antiinflammatory activities of an aqueous extract of Phellinus gilvus (PG) against carrageenan- and cotton pellet-induced acute and chronic inflammation in rats. Four acute and chronic inflammation groups included the vehicle control group, positive control group (aminopyrine, 100 mg/kg), PG10 group (PG, 10 mg/kg), and PG20 group (PG, 20 mg/kg). Oral administration of PG extract produced dose-dependent antiinflammatory effects in both the acute and chronic groups. In the carrageenan-induced paw edema, significant inhibitions were observed at 0.5 and 1 hr in the PG10 group and at 0.5, 1, 2, 4, 5, and 6 hr in the PG20 group. In the cotton pellet-induced granuolma formation, PG extract at 10 and 20 mg/kg per day also showed significant inhibition in the wet and dry weights of granuloma. The free radical scavenging assay indicated a dose-dependent scavenging activity of PG against 2,2-diphenyl-1-picrylhydrazyl free radicals. PG extract may be beneficial as an antiinflammatory agent by virtue of antioxidant action.

The short-term toxicity of PAI-N002, a mixture of Schizandra chinensis, Astragalus membranaceus, Artemisia capillaris, and Coriolus versicolor extracts (1 : 1 : 1 : 1), was evaluated in rats. This study also investigated the protective effect of PAI-N002 on liver injury induced by the co-administration of ethanol and carbon tetrachloride (EC) in rats. PAI-N002 was virtually non-toxic to rats after a single oral administration, with LD50 values > 5,000 mg/kg. The subacute toxicity study showed that 2-week repeated oral dose of PAI-N002 did not cause any adverse effects on clinical signs, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross findings, and organ weights in rats given up to 1,000 mg/kg/day. When rats with EC-induced hepatotoxicity were treated with PAI-N002 at 250 mg/kg/day for 28 days, PAI-N002 treatment significantly improved EC-induced hepatic injury, as evidenced by the decline of serum AST and ALT activities and decreased histopathological alterations. PAI-N002 also had an antioxidant benefit by decreasing the lipid peroxidative product malondialdehyde and increasing the levels of the antioxidant glutathione and the activities of the antioxidant enzymes catalase, superoxide dismutase, and glutathione-S-transferase. These results indicate that the short-term treatment of rats with PAI-N002 has no harmful effects and that PAI-N002 has hepatoprotective and antioxidant properties in EC-induced chronic liver injury in rats.

This study investigated the effects of epichlorohydrin (ECH) on spermatogenesis and antioxidant system in rats. An increase in the incidence of clinical signs, gross pathology and histopathology findings in the epididymidis, and sperm abnormalities and a decrease in the testicular spermatid counts, epididymal sperm counts, and sperm motility were observed at 30 mg/kg/day. Oxidative stress in the epididymal tissue was detected ator =3.3 mg/kg/day. The results show that graded doses of ECH elicit depletion of antioxidant defense system and that the adverse effects on male reproductive function in ECH-treated rats may be due to the induction of oxidative stress.

We have recently reported that the continuous exposure of rats to a concrete building environment under cool temperatures had adverse effects on general health parameters and embryo-fetal development. This study examined to compare the potential effects of concrete and wood building environments on pregnant dams and embryo-fetal development in rats. Groups of 10 mated females were exposed to polycarbonate (control), concrete, or wood cages from gestational days (GD) 0 to 20 under cool temperatures (11.9∼12.3°C). All the females underwent a caesarean section on GD 20, and their fetuses were examined for any morphological abnormalities. The temperatures in the cages were similar in all groups but the relative humidity in the concrete and wood groups were higher than in the control group. The concentration of volatile organic compounds in the wood group was higher than in the control group. In the concrete group, maternal effects manifested as an increase in the incidence of clinical signs, a lower body weight, and a decrease in the thymus and ovary weights. Developmental effects included increased post-implantation loss and decreased litter size. Infrared thermal analysis showed that the skin temperature of the rats in the concrete group was lower than that in the control group. In contrast, there were no exposure-related adverse effects on the maternal and developmental parameters in the wood group. Overall, the exposure of pregnant rats to a concrete building environment under cool temperatures has adverse effects on the clinical signs, body weight, skin temperature, organ weight, and embryo-fetal development. On the other hand, exposure to a wood building environment does not have any adverse effects in rats.

Present study was conducted to investigate potential effects of epichlorohydrin on testicular and epididymal function in male rats. The test chemical was administered to adult male rats by gavage at dose levels of 0, 3.125, 12.5, and 50 mg/kg/day for 7 days. Testicular and epididymal function were assessed by measurement of reproductive organ weight, testicular spermatid count, epididymal sperm count, motility and morphology, and histopathology in rats. At 50 mg/kg, a decrease in the sperm motility and an increase in the incidence of sperm abnormalities were observed. Histopatho-logical examinations revealed an increase in the incidence of histopathological changes including cell debris in the ducts, vacuolization of the epithelial cells, oligospermia, and epithelial disruption in the proximal caput epididymidis. At 12.5 mg/kg, an increase in the incidence of histopathological changes of the epididymidis was found. There were no treatment-related effects at 3.125 mg/kg. These results show that 7-day repeated oral administration of epichlorohydrin to male rats results in adverse effects on sperm motility, sperm morphology, and epididymal histology at ≥ 12.5 mg/kg/day.

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity

This study was conducted to investigate the potential effects of α-chlorohydrin (ACH) on epididymal function and antioxidant system in male rats. The test chemical was administered to male rats by gavage at doses of 0, 3, 10, and 30 mg/kg/day for 7 days. Twenty-four male rats were randomly assigned to four experimental groups, with six rats in each group. Spermatotoxicity was assessed by measurement of reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, histopathologic examination, and oxidative damage analysis in rats. At 30 mg/kg/day, an increase in the incidence of clinical signs, epididymis weight, and gross necropsy findings of the epididymis, a decrease in the sperm motility, and an increased incidence of histopathological changes of the epididymis were observed in a dose-dependent manner. At 10 mg/kg/day, an increased incidence of clinical signs and histopathological changes and decreased sperm motility were observed. In the oxidative damage analysis, an increase in the malondialdehyde concentration and a decrease in the glutathione content and glutathione peroxidase and catalase activities in the epididymal tissue were detected at ≥3 mg/kg/day. The results show that graded doses of ACH elicit depletion of the antioxidant defense system and that the spermatotoxicity of ACH may be due to the induction of oxidative stress.

BACKGROUND: Although the potential risk of carbon nanotubes (CNTs) to humans has recently increased due to expanding production and widespread use, the potential adverse effects of CNTs on embryo–fetal development have not yet been determined. METHODS: This study investigated the potential effects of multi-wall CNTs (MWCNTs) on pregnant dams and embryo–fetal development in rats. MWCNTs were administered to pregnant rats by gavage at 0, 40, 200, and 1,000 mg/kg/day. All dams were subjected to Cesarean section on day 20 of gestation, and the fetuses were examined for any morphological abnormalities. RESULTS: All animals survived to the end of the study. A decrease in thymus weight was observed in the high dose group in a dose-dependent manner. However, maternal body weight, food consumption, and oxidant–antioxidant balance in the liver were not affected by treatment with MWCNTs. No treatment-related differences in gestation index, fetal deaths, fetal and placental weights, or sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in incidences of abnormalities between the groups. CONCLUSIONS: The results show that repeated oral doses of MWCNTs during pregnancy induces minimal maternal toxicity and no embryo–fetal toxicity at 1,000 mg/kg/day in rats. The no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1,000 mg/kg/day for embryo–fetal development. In this study, the dosing formulation was not analyzed to determine the degree of reaggregation (or not), nor were blood levels of CNT's measured in the dosed animals to verify or characterize absorption. Birth Defects Res (Part B) 92:69–76, 2011. © 2011 Wiley-Liss, Inc.

Allyl isothiocyanate (AITC) and phenethyl isothiocyanate (PEITC) were isolated from Sinapis alba L. seeds and their effects against Dermatophagoides farinae and D. pteronyssinus were evaluated using the impregnated fabric disk method. The LD 50 values of their compounds and derivatives were then compared with those of a commercial acaricide, benzyl benzoate. On the basis of the LD 50 values against D. farinae, PEITC (0.21 microg/cm(2)) was the most toxic, followed by benzyl isothiocyanate (0.55 microg/cm(2)), phenyl isothiocyanate (1.09 microg/cm(2)), butyl isothiocyanate (1.24 microg/cm(2)), and AITC (1.36 microg/cm(2)); acetyl isothiocyanate (195.01 microg/cm(2)) was the least toxic. In addition, the acaricidal effects of AITC and PEITC against D. farinae were 7.4- and 47.8-fold greater than those of benzyl benzoate, respectively. Against D. pteronyssinus, PEITC was the most toxic (0.19 microg/cm(2)), followed by benzyl isothiocyanate (0.77 microg/cm(2)), phenyl isothiocyanate (1.37 microg/cm(2)), butyl isothiocyanate (1.50 microg/cm(2)), and AITC (2.88 microg/cm(2)); acetyl isothiocyanate (168.82 microg/cm(2)) was the least toxic. AITC and PEITC were 3.3- and 50.4-fold more active than benzyl benzoate against D. pteronyssinus, respectively. Taken together, these findings indicate that AITC, PEITC, and partial derivatives may be useful as preventive agents against dust mites. In addition, these results indicate that structure-activity is related to the aromatic structure, the number of carbon atoms, and the compounds hydrophobicity.

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Yu-Ri Kim,4 Meyoung-Kon Kim,4 Jong-Kwon Lee,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, 2College of Veterinary Medicine, Konkuk University, Seoul, 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, 6College of Veterinary Medicine, Chonnam National University, Gwangju, Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnOSM20[-] NPs; negatively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague Dawley rats. ZnOSM20(-) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnOSM20(-) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day. Keywords: nanotoxicology, nanoparticles, zinc oxide, maternal toxicity, developmental toxicity, teratogenicity