Hyun-Mi Kim

Combined repeated-dose toxicity study of silver nanoparticles with the reproduction/developmental toxicity screening test

Abstract Combined repeated-dose toxicity study of citrate-capped silver nanoparticles (7.9 ± 0.95 nm) with reproduction/developmental toxicity was investigated in rats orally treated with 62.5, 125 and 250 mg/kg, once a day for 42 days for males and up to 52 days for females. The test was performed based on the Organization for Economic Cooperation and Development test guideline 422 and Good Laboratory Practice principles. No death was observed in any of the groups. Alopecia, salivation and yellow discolouration of the lung were observed in a few rats but the symptoms were not dose-dependent. Haematology, serum biochemical investigation and histopathological analysis revealed no statistically significant differences between control group and the treated groups. Toxicity endpoints of reproduction/developmental screening test including mating, fertility, implantation, delivery and foetus were measured. There was no evidence of toxicity.

Potential Toxicity of Differential Functionalized Multiwalled Carbon Nanotubes (MWCNT) in Human Cell Line (BEAS2B) and Caenorhabditis elegans

The aim of this study was to evaluate in vitro (human bronchial epithelial cells, BEAS2B cells) and in vivo (the nematode Caenorhabditis elegans, C. elegans) toxicity outcomes following exposure to pristine as well as surface-functionalized multiwalled carbon nanotubes (MWCNT) following hydroxylation-oxygenation (O+), amination (NH2), or carboxylation (COOH) of the carbon nanotubes (CNT). Cell viability and proliferation were measured by Ez-Cytox, trypan blue exclusion, and colony formation assays. The genotoxic potential of the MWCNT was determined by using the alkaline comet assay. In addition, survival and reproduction were used as endpoints for detection of toxicity of MWCNT in C. elegans. The carboxylated (COOH)-MWCNT was found most toxic as evidenced by cytotoxic and genotoxic among all tested compounds. The order of sensitivity was COOH > O+ > NH2 > pristine. There were almost no marked changes in survival following exposure of C. elegans to MWCNT. It is of interest that only pristine MWCNT exerted significant reduction in reproductive capacity of C. elegans. Surface functionalization significantly influenced the bioactivity of MWCNT, which displayed species as well as target-organ specificity. The mechanisms underlying these specific modes of nano-biological interactions need to be elucidated.

Aluminum Nanoparticles Induce ERK and p38MAPK Activation in Rat Brain

Aluminum nanoparticles (Al-NPs) are one of the most widely used nanomaterial in cosmetics and medical materials. For this reason, Al-NP exposure is very likely to occur via inhalation in the environment and the workplace. Nevertheless, little is known about the mechanism of Al-NP neurotoxicity via inhalation exposure. In this study, we investigated the effect AL-NPs on the brain. Rats were exposed to Al-NPs by nasal instillation at 1 mg/kg body weight (low exposure group), 20 mg/kg body weight (moderate exposure group), and 40 mg/kg body weight (high exposure group), for a total of 3 times, with a 24-hr interval after each exposure. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that the presence of aluminum was increased in a dose-dependent manner in the olfactory bulb (OFB) and the brain. In microarray analysis, the regulation of mitogen-activated protein kinases (MAPK) activity (GO: 0043405), including Ptprc, P2rx7, Map2k4, Trib3, Trib1, and Fgd4 was significantly over-expressed in the treated mice than in the controls (p = 0.0027). Moreover, Al-NPs induced the activation of ERK1 and p38 MAPK protein expression in the brain, but did not alter the protein expression of JNK, when compared to the control. These data demonstrate that the nasal exposure of Al-NPs can permeate the brain via the olfactory bulb and modulate the gene and protein expression of MAPK and its activity.

Evaluation of toxicity to triclosan in rats following 28 days of exposure to aerosol inhalation

The present study was conducted to investigate the potential subchronic toxicity of triclosan (TCS) in rats following 28 days of exposure by repeated inhalation. Four groups of six rats of each sex were exposed to TCS-containing aerosols by nose-only inhalation of 0, 0.04, 0.13, or 0.40 mg/L for 6 h/day, 5 days/week over a 28-day period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. At 0.40 mg/L, rats of both sexes exhibited an increase in the incidence of postdosing salivation and a decrease in body weight. Histopathological alterations were found in the nasal septum and larynx. There were no treatment-related effects in rats of either sex at ⩽0.13 mg/L. Under the present experimental conditions, the target organs in rats were determined to be the nasal cavity and larynx. The no-observed-adverse-effect concentration in rats was determined to be 0.13 mg/L.

Ethylene glycol potentiated didecyldimethylammonium chloride toxicity in human bronchial epithelial cells

Didecyldimethylammonium chloride (DDAC) is an antimicrobial agent used as a preservative in household products. DDAC is toxic in human lung cells and in mouse lung. Aerosol products that contain DDAC often include ethylene glycol (EG) as a solvent; no safety information is available for respiratory toxicity of this combination (DDAC and EG). Human bronchial epithelial cells (BEAS-2B) were exposed (24 h) to DDAC and EG, separately or together. DDAC showed concentration-dependent cytotoxicity. EG did not affect cell viability. Compared to DDAC alone, EG and DDAC together enhanced mitochondrial damage and cell membrane disruption. Increased reactive oxygen species and decreased glutathione levels were seen in cells treated with the combination. Intracellular DDAC concentrations were elevated in the presence of EG. EG potentiated DDAC toxicity in lung cells by inducing oxidative stress through enhanced cellular uptake of DDAC. The use of these chemicals together in spray-type products should be carefully considered.

Didecyldimethylammonium chloride induces oxidative stress and inhibits cell growth in lung epithelial cells

Didecyldimethylammonium chloride (DDAC) is a commonly used biocide that can cause lung inflammation and fibrosis. However, the mechanism of this pulmonary toxicity is unclear. Thus, we examined the mechanism for the DDAC-induced pulmonary toxicity at the cellular level by using lung epithelial cells. DDAC induced cell damage, including injury of mitochondria and lysosomes with the release of lactate dehydrogenase (LDH), as well as caused cell morphological changes and necrotic reactions. In a clonogenic assay, treatment with a low concentration of DDAC (5 μM) for 10 days reduced both the number and size of the colonies, which are indexes of cell growth. In addition, DDAC increased intracellular reactive oxygen species (ROS) production while it decreased glutathione (GSH) activity. Therefore, our results suggest that exposure to even a low concentration of DDAC may inhibit cell growth and cause oxidative stress in lung epithelial cells.

Investigation of disinfectants for foot-and-mouth disease in the Republic of Korea

Disinfectants for foot-and-mouth disease were sprayed on livestock barns and roads from early February to May 2011. Although 90% of the disinfectant was concentrated on the roads, 10% was sprayed on cattle sheds and other sites where foot-and-mouth disease occurred. Since the outbreak of foot-and-mouth disease in November 2010, there has been a steady increase in disinfectant use. Consequently, its adverse environmental effects have prompted government officials to take preventive measures. The major chemical components of the disinfectants are citric acid, potassium sulfate base complex, quaternary ammonium compound, malic acid, and glutaraldehyde, ranging in amounts from tons to hundreds of tons. The exact amount of each component of the disinfectants could not be identified because the types of components used in the different commercial formulations overlapped. In this review, we obtained information on disinfectants that are widely used nationwide, including the types of major chemical components and their respective toxicities (both human and ecological).

Combined repeated dose and reproductive/developmental toxicities of copper monochloride in rats.

This study investigated the combined repeated dose and reproductive/developmental toxicity of copper monochloride in rats. The test substance was administered once daily by gavage at 0, 1.3, 5, 20, or 80 mg/kg/day. Male rats were dosed for a total of 30 days beginning 14 days before mating. Female rats were dosed from 2 weeks before mating to day 3 of lactation throughout the mating and gestation period. At 80 mg/kg/day, deaths were observed in 3 out of 12 females. There was a dose‐dependent increase in the incidence of clinical signs and a reduction in the food consumption. Hematological and serum biochemical investigations revealed a decrease in the red blood cell, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin (MCH), and serum total protein levels and an increase in the white blood cell and platelets in males, and a decrease in the MCH and an increase in the platelets in females. Histopathological examination showed an increased incidence of squamous cell hyperplasia of the stomach in both genders as well as increased hematopoiesis of the femur in males. There was an increase in the number of icteric and runt pups at birth. At 20 mg/kg/day, there was an increase in the incidence of clinical signs and squamous cell hyperplasia of the stomach in both genders. At 5 mg/kg/day, an increase in the incidence of squamous cell hyperplasia of the stomach was observed in females. There were no adverse effects in the lowest group in both genders. Based on these findings, the no‐observed‐adverse‐effect levels of copper monochloride were concluded to be 5 mg/kg/day in male rats and 1.3 mg/kg/day in female rats for general toxicity and 20 mg/kg/day for reproductive/developmental toxicity.

Safety evaluation of zinc oxide nanoparticles in terms of acute dermal toxicity, dermal irritation and corrosion, and skin sensitization

To clarify the health risks related to the use of zinc oxide (ZnO) nanoparticles, acute dermal toxicity, dermal irritation and corrosion, and skin sensitization were evaluated according to the guideline for Organization for Economic Cooperation and Development (OECD) and Good Laboratory Practice (GLP). In acute dermal toxicity test using rats, there were no treatment-related mortality, clinical signs of toxicity, body weight changes, and gross findings at a dose level of 2000 mg/kg. Similarly, dermal irritation and corrosion tests using rabbits revealed no mortality, clinical signs of toxicity, and acute irritation or corrosion reaction on the skin. In a skin sensitization test using guinea pigs, there were no significant mortality, clinical signs of toxicity, body weight changes, and skin reactions 24 and 48 h after the removal of challenge patch, which was scored “0” based on the Magnusson and Kligman grading scale. Our findings suggest that the nano-sized ZnO used in this study is relatively safe since it did not induce acute dermal toxicity, dermal irritation and corrosion, and skin sensitization.

Analysis of microRNA and gene expression profiling in triazole fungicide-treated HepG2 cell line.

MicroRNA (miRNA) plays an important role in various diseases and in cellular and molecular responses to toxicants. In the present study, we investigated differential expression of miRNAs in response to three triazole fungicides (myclobutanil, propiconazole, and triadimefon). The human hepatoma cell line (HepG2) was treated with the above triazoles for 3 h or 48 h. miRNA-based microarray experiments were carried out using the Agilent human miRNA v13 array. At early exposure (3h), six miRNAs were differentially expressed and at late exposure (48 h), three miRNAs were significantly expressed. Overall, this study provides an array of potential biomarkers for the above triazole fungicides. Furthermore, these miRNAs induced by triazoles could be the foundation for the development of a miRNA-based toxic biomarker library that can predict environmental toxicity.