Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats.

BACKGROUND: Although biocides at low concentrations have been used to control pests, they can be more harmful than industrial chemicals as humans are directly and frequently exposed to such biocides. Benzalkonium chloride (BAC or BKC) is a non-toxic substance used to control pests. Recently, BAC has been increasingly used as a component in humidifier disinfectants in Korea, raising a serious health concern. Moreover, it poses significant health hazards to workers handling the chemical because of direct exposure. In the present study, we aimed to evaluate the respiratory toxicity of BAC due to its inhalation at exposure concentrations of 0.8 (T1 group), 4 (T2 group) and 20 (T3 group) mg/m3. RESULTS: In our previous study on the acute inhalational toxicity of BAC, bleeding from the nasal cavity was observed in all the rats after exposure to 50 mg/m3 BAC. Therefore, in this study, 20 mg/m3 was set as the highest exposure concentration, followed by 4 and 0.8 mg/m3 as the medium and low concentrations for 6 h/day and 14 days, respectively. After exposure, recovery periods of 2 and 4 weeks were provided. Additionally, alveolar lavage fluid was analyzed in males of the BAC-exposed groups at the end of exposure and 2 weeks after exposure to evaluate oxidative damage. In the T3 group exposed to BAC, deep breathing, hoarseness, and nasal discharge were observed along with a decline in feed intake and body weight, and nasal discharge was also observed in the T1 and T2 groups. ROS/RNS, IL-1ß, IL-6, and MIP-2 levels decreased in a concentration-dependent manner in the bronchoalveolar lavage fluid. Histopathological examination showed cellular changes in the nasal cavity and the lungs of the TI, T2, and T3 groups. CONCLUSIONS: As a result, it was confirmed that the target organs in the respiratory system were the nasal cavity and the lungs. The adverse effects were evaluated as reversible responses to oxidative damage. Furthermore, the no observed adverse effect level was found to be less than 0.8 mg/m3 and the lowest benchmark dose was 0.0031 mg/m3. Accordingly, the derived no-effect level of BAC was calculated as 0.000062 mg/m3.

Assessment of cyclohexanone toxicity in inhalation-exposed F344 rats and B6C3F1 mice: applications in occupational health.

BACKGROUND: Cyclohexanone is a chemical used in various industries and many workers are exposed to it. Therefore, in this study, we determined the toxicity of cyclohexanone in inhalation-exposed F344 rats and B6C3F1 mice, so as to apply the findings in hazard and risk assessments. METHODS: Ten male and 10 female rats and mice per test group were exposed to cyclohexanone vapors at 0, 100, 250, and 625 ppm concentrations for 6 h per day, 5 d per week, and for 13 weeks. All rats and mice were killed after the exposure period. Clinical signs, body weight, feed intake, and ophthalmoscopy findings were recorded during the exposure period, and hematology, blood biochemistry, organ weights, gross findings, and histopathology were evaluated thereafter. RESULTS: The following findings were noted in cyclohexanone-exposed F344 rats: increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increased liver weight, and bile duct hyperplasia in the males exposed to 250 and 625 ppm cyclohexanone, increased ALT levels and bile duct hyperplasia in the females exposed to 625 ppm cyclohexanone, and increased blood urea nitrogen (BUN) and tubular basophilia in the renal cortex in the males exposed to 625 ppm cyclohexanone. On the other hand, B6C3F1 mice exposed to cyclohexanone showed no obvious exposure-related effects. CONCLUSION: Based on the findings, the no-observed-adverse-effect level (NOAEL) was determined to be 100 ppm in F344 rats and >625 ppm in B6C3F1 mice. Therefore, 2 ppm was revealed as the derived no-effect level (DNEL) for cyclohexanone.

Subchronic oral toxicity study of Korean red ginseng extract in Sprague-Dawley rats with a 4-week recovery period.

Ginseng is a major herbal remedy used in Asian countries for thousands of years and known to restore and enhance vital energy. Korean red ginseng, which is processed by steaming and drying fresh Panax ginseng, is most popular and contains unique ginsenosides, which have anticancer and anti-inflammatory properties. The present study was carried out to evaluate the repeated oral dose toxicity of Korean red ginseng extract. The test article was administered orally once a day to male and female Sprague-Dawley rats at dose levels of 0, 500, 1000, or 2000 mg/kg/day for 13 consecutive weeks (15 animals/sex/group in the vehicle control and 2000 mg/kg/day groups, and 10 animals/sex/group in the 500 and 1000 mg/kg/day groups). Ten animals per group were sacrificed at the end of the 13-week treatment period, and the remaining rats were sacrificed after a 4-week recovery period. Administration of Korean red ginseng extract did not result in any toxicologically significant changes in mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights, or histopathology. It was established that the no observed adverse effect level (NOAEL) of the test article was 2000 mg/kg/day for both sexes in this study.

Qualitative and quantitative analysis of flavonoids from 12 species of Korean mulberry leaves.

The total flavonoids in leaves of 12 varieties of Korean mulberry (Morus alba L.) were determined. Seventeen flavonoids were isolated and analyzed using ultra-performance liquid chromatography coupled with diode array detection and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF/MS). To determine the flavonoid contents, HPLC analysis was performed on these 17 flavonoids. The total flavonoid contents of the 12 varieties of mulberry leaves ranged from 748.5 to 1297.9 mg, with the highest obtained from the Cheong Su variety (1297.9 ± 112.0 mg). Among the 17 flavonoids analyzed, quercetin 3-O-rutinoside (rutin) and quercetin 3-O-glucoside (isoquercitrin) had highest contents in the Cheong Su variety. Furthermore, the Dae Dang Sang variety gave the highest quercetin 3-O-rutinoside (rutin) content among the mulberry leaves investigated, at 425.5 ± 45.9 mg. Major flavonols from Dae Dang Sang were detected by UPLC-DAD-QTOF/MS. A total of 17 flavonoid compound peaks were identified in the analysis time range of 5-40 min, all of which were kaempferol and quercetin glycosides. Seven of the 17 compounds identified in mulberry leaves were unknown.

Twenty-eight-day repeated inhalation toxicity study of nano-sized lanthanum oxide in male sprague-dawley rats.

Although the use of lanthanum has increased in field of high-tech industry worldwide, potential adverse effects to human health and to the environment are largely unknown. The present study aimed to investigate the potential toxicity of nano-sized lanthanum oxide (La2 O3 ) following repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed nose-only to nano-sized La2 O3 for 28 days (5 days/week) at doses of 0, 0.5, 2.5, and 10 mg/m3 . In the experimental period, we evaluated treatment-related changes including clinical signs, body weight, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology findings. We also analyzed lanthanum distribution in the major organs and in the blood, bronchoalveolar lavage fluids (BALF), and oxidative stress in lung tissues. Lanthanum level was highest in lung tissues and showed a dose-dependent relation. Alveolar proteinosis was observed in all treatment groups and was accompanied by an increase in lung weight; moreover, lung inflammation was observed in the 2.5 mg/m3 and higher dose groups and was accompanied by an increase in white blood cells. In the BALF, total cell counts including macrophages and neutrophils, lactate dehydrogenase, albumin, nitric oxide, and tumor necrosis factor-alpha increased significantly in all treatment groups. Furthermore, these changes tended to deteriorate in the 10 mg/m3 group at the end of the recovery period. In the present experimental conditions, we found that the lowest-observed-adverse-effect level of nano-sized La2 O3 was 0.5 mg/m3 in male rats, and the target organ was the lung. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1226-1240, 2017.

Size-dependent clearance of gold nanoparticles from lungs of Sprague-Dawley rats after short-term inhalation exposure.

Gold nanoparticles are known to be distributed to many tissues following their oral, inhalation, or intravenous exposure. Information on the biodistribution and clearance of gold nanoparticles from these tissues is, therefore, important to understand their behavior in vivo. To study the effect of size on the biodistribution of gold nanoparticles, Sprague-Dawley rats were exposed by inhalation to small gold nanoparticles (13 nm in diameter on average) at an exposure concentration of 12.8 ± 2.42 µg/m(3), and to large gold nanoparticles (105 nm in diameter on average) at an exposure concentration of 13.7 ± 1.32 µg/m(3). The experimental animals were exposed to the gold nanoparticles and the control animals to fresh air for 5 days (6 h/day), followed by a recovery period of 1, 3, and 28 days in fresh air. None of the exposed animals exhibited any toxic response to the gold nanoparticles. Despite the difference in size, both small and large gold nanoparticles deposited mainly in rat lungs. Their biodistribution from the lungs to secondary target organs was significantly higher with the small compared to the large gold nanoparticles. While the large gold nanoparticles were only found in the blood, the small gold nanoparticles were detected in the liver, spleen, brain, testes, and blood. In addition, the elimination half-life of the small gold nanoparticles from the lungs was significantly shorter than that of the large gold nanoparticles. The present data may, therefore, suggest that the smaller gold nanoparticles are able to translocate from the lungs, the primary exposure organ to extrapulmonary organs at a faster rate than the larger gold nanoparticles and thus confirming previous observations reported in the literature.

Negligible Pharmacokinetic Interaction of Red Ginseng and Losartan, an Antihypertensive Agent, in Sprague-Dawley Rats.

Red ginseng (RG) is one of the top selling herbal medicines in Korea, but is not recommended in hypertensive patients. In this study, the pharmacokinetic (PK) interaction between RG and losartan, an antihypertensive drug, was examined. RG was orally administered for 2 wk to male Sprague-Dawley (S-D) rats at either control (0), 0.5, 1, or 2 g/kg/d for 2 wk. After the last administration of RG and 30 min later, all animals were treated with 10 mg/kg losartan by oral route. In addition, some S-D rats were administered RG orally for 21 d at 2 g/kg followed by losartan intravenously (iv) at 10 mg/kg/d. Post losartan administration, plasma samples were collected at 5, 15, and 30 min and 1, 1.5, 2, 3, 6, 12, and 24 h. Plasma concentrations of losartan and E-3174, the active metabolite of losartan, were analyzed by a high-pressure liquid chromatography-tandem mass spectrometer system (LC-MS/MS). Oral losartan administration showed dose-dependent pharmacokinetics (PK) increase with time to maximum plasma, but this was not significant between different groups. There was no significant change in tmax with E-3174 PK. With iv losartan, pharmacokinetics showed elevation of area under the plasma concentration-time curve from time zero extrapolated to infinitity. There was not a significant change in AUCinf with E-3174 PK. Therefore, RG appeared to interfere with biotransformation of losartan, as RG exerted no marked effect on E-3174 PK in S-D rats. Data demonstrated that oral or iv treatment with losartan in rats pretreated with RG for 2 wk showed that losartan PK was affected but E-3174 PK remained unchanged among different dose groups. These results suggested that RG induces negligible influence on losartan and E-3174 PK in rats.

Negligible pharmacokinetic interaction of red ginseng and antihypertensive agent amlodipine in Sprague-Dawley rats.

Red ginseng (RG) is the top-selling functional food in Korea, but is not recommended for use in hypertensive patients. This study was performed to determine the pharmacokinetic (PK) interaction between RG and amlodipine, an antihypertensive drug. RG (0, 0.5, 1, or 2 g/kg/d) was administered orally for 2 wk, and then amlodipine (10 mg/kg) was given orally, to Sprague-Dawley (SD) rats. Blood was collected at 0.08, 0.25, 1, 1.5, 2, 3, 6, 12, and 24 h after amlodipine administration. In intravenous (iv) study, RG (0, 1, or 2 g/kg/d) was administered orally to SD rats for 2 wk, followed by amlodipine (2 mg/kg) intravenously (iv). Plasma concentrations of amlodipine were analyzed using a high-pressure liquid chromatography-tandem mass system (LC-MS/MS). Oral administration of amlodipine produced an increase of time to maximum plasma concentration (tmax: 2.6, 4.1, 8.3, and 8.9 h at 0, 0.5, 1, and 2 g/kg/d, respectively), and a decrease of maximum plasma concentration (Cmax: 278.5, 212.4, 232.1, and 238.7 ng/ml at 0, 0.5, 1, and 2 g/kg/d, respectively.). However, the area under the concentration-time curve from time 0 to 24 h measurable concentration (AUC0-24 h was 3487.4, 2895.4, 3158.2, and 3495 ng/h/ml at 0, 0.5, 1, and 2 g/kg/d respectively) was not significantly changed among the different dose groups. Administration of amlodipine iv produced no significant changes in the apparent terminal half-life, volume of distribution, and AUC0-24 hr among the different dose groups. These results suggest that RG induced negligible influence on amlodipine pharmacokinetically in rats.

Biopersistence of silver nanoparticles in tissues from Sprague-Dawley rats.

Silver nanoparticles are known to be distributed in many tissues after oral or inhalation exposure. Thus, understanding the tissue clearance of such distributed nanoparticles is very important to understand the behavior of silver nanoparticles in vivo. For risk assessment purposes, easy clearance indicates a lower overall cumulative toxicity. Accordingly, to investigate the clearance of tissue silver concentrations following oral silver nanoparticle exposure, Sprague-Dawley rats were assigned to 3 groups: control, low dose (100 mg/kg body weight), and high dose (500 mg/kg body weight), and exposed to two different sizes of silver nanoparticles (average diameter 10 and 25 nm) over 28 days. Thereafter, the rats were allowed to recover for 4 months. Regardless of the silver nanoparticle size, the silver content in most tissues gradually decreased during the 4-month recovery period, indicating tissue clearance of the accumulated silver. The exceptions were the silver concentrations in the brain and testes, which did not clear well, even after the 4-month recovery period, indicating an obstruction in transporting the accumulated silver out of these tissues. Therefore, the results showed that the size of the silver nanoparticles did not affect their tissue distribution. Furthermore, biological barriers, such as the blood-brain barrier and blood-testis barrier, seemed to play an important role in the silver clearance from these tissues.

Moral sensitivity relating to the application of the code of ethics.

This study investigated the clinical application of the 2006 Third Revised Korean Nurses' Code of Ethics and the moral sensitivity of nurses. A total of 303 clinical nurses in South Korea participated in the survey in May and June 2011. As instruments of this study, we used the 15 statements of the Korean Nurses' Code of Ethics and Korean Moral Sensitivity Questionnaire. The mean score for application was 3.77 ± 0.59 (out of 5), and the mean score for moral sensitivity was 5.14 ± 0.55 (out of 7). The correlation coefficient (r) of the application and moral sensitivity was 0.336 (p < 0.001). Nurses who scored high on moral sensitivity also scored high on application (t = -5.018, p < 0.001). In clinical settings, educational programmes to develop the moral sensitivity of nurses are necessary for improving the application of the code of ethics.

The effects of 4-week inhalation exposure to titanium nitride on lungs of Sprague-Dawley rats.

Titanium nitride (TiN) is a ceramic material with physical properties such as extreme hardness, high decomposition temperature, defect structure, and gold-yellow color. TiN is generally considered non-toxic and safe; however, hazards have not been identified, especially in workers after inhalation exposure. Here, we conducted a four-week inhalation toxicity study of TiN using a nose-only inhalation exposure system in Sprague-Dawley rats. Rats were exposed to TiN for 4 weeks (6 h a day, 5 days per week) at target concentrations of 45, 90, and 180 mg/m3. Clinical signs, mean body weight changes, hematology, blood biochemistry, necropsy, organ weight, bronchoalveolar lavage fluid analysis, and histopathological findings were observed. Analytical concentrations of the low, middle, and high-concentration groups were 45.55 ± 3.18 mg/m3, 90.69 ± 7.30 mg/m3, and 183.87 ± 15.21 mg/m3, respectively. The mass median aerodynamic diameter (MMAD) for the low, middle, and high-concentration groups were 1.44 ± 0.07 µm, 1.47 ± 0.18 µm, and 1.68 ± 0.16 µm, and the geometric standard deviation (GSD) was 2.24 ± 0.03, 2.31 ± 0.16, and 2.43 ± 0.11, respectively. No systemic adverse effects were observed after inhalation exposure to TiN; however, histopathological findings (increased phagocytic macrophages and alveolar/bronchiolar epithelial hyperplasia) and Bronchoalveolar Lavage Fluid (BALF) analysis (elevated lactate dehydrogenase and gamma-glutamyltransferase values) showed adverse effects on the lungs in the middle and high-concentration groups. Based on these results, the no observed adverse effect concentration (NOAEC) is suggested to be 45 mg/m3.

N-methylformamide induces multiple organ toxicity in Fischer 344 rats.

N-Methylformamide (NMF) is a widely used chemical (CAS No.: 123-39-7) in several industries and its usage is continuously increasing. However, studies for NMF have been focused on hepatotoxicity from now. Its toxicity profile has not yet been established owing to limited toxicity data. Therefore, we evaluated systemic toxicity via NMF inhalation. We exposed 0, 30, 100, and 300 ppm NMF to Fischer 344 rats for 6 h/day, 5 days a week for 2 weeks. Clinical signs, body weights, food consumption, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathology were performed. Two females exposed to 300 ppm NMF died during exposure period. Decrease of food consumption and body weight in both sexes exposed to 300 ppm in females exposed to 100 ppm were noted during exposure period. Increased RBC and HGB were noted in females exposed to 300 ppm. A decrease in the levels of ALP and K and increase in the levels of TCHO and Na were observed in both sexes exposed to 300 and 100 ppm. Increased levels of ALT, AST, BUN and decreased levels of TP, ALB, Ca were observed in females exposed to 300 and 100 ppm. The relative liver weight was elevated in both sexes exposed to 300 and 100 ppm NMF. Hypertrophy in the liver and submandibular glands and nasal cavity injuries were noted in both sexes exposed to 300 and 100 ppm NMF. Tubular basophilia of the kidneys were noted in females exposed to 300 ppm NMF. We revealed that NMF affect several organs including the kidneys not only the liver and NMF-related toxicity is predominant in female rats. These results could contribute to the development of NMF toxicity profile and may help in developing strategies for the control of occupational environmental hazards related to NMF.

Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of Locusta migratoria (Orthoptera: Acrididae) as a novel food source.

The migratory locust, Locusta migratoria (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of L. migratoria had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of L. migratoria (fdLM) and identify allergic components in ELISA and PCR techniques. In this subchronic study, fdLM was administered once daily by oral gavage at the doses of 750, 1500, and 3000 mg/kg/day. No toxicological changes were observed in both sexes of rats for 13 weeks in accordance with the OECD guidelines and GLP conditions. In addition, fdLM did not induced increases of serum immunoglobulin E and 21 homologous proteins were not detected under our present conditions. In conclusion, the NOAEL (no-observed-adverse-effect level) was 3000 mg/kg/day and no target organ was identified in both sexes. In conclusion, we found that fdLM is safe with no adverse effects and offers the potential of its use as an edible ingredient or other biological uses.

Hepatoprotective effects on alcoholic liver disease of fermented silkworms with Bacillus subtilis and Aspergillus kawachii.

The purpose of this study was to investigate the protective effect of Bacillus subtilis fermented silkworm powder (BFSP) and Aspergillus kawachii fermented silkworms powder (AFSP) on alcohol-induced hepatotoxicity in Sprague-Dawley rats. Alcohol-feeding rats were fed with diets containing silkworm powder (SP) or both BFSP and AFSP at the 5% (w/w) levels for 4 weeks. Alcohol administration resulted in a significant increase in the activities of liver marker enzymes, aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and lactate dehydrogenase (LDH). Administration of BFSP markedly prevented alcohol-induced elevation of serum AST, γ-GTP and LDH activities, and the levels of blood alcohol and acetaldehyde. Interestingly, in comparison with both SP and AFSP, BFSP administration drastically increased both hepatic alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities, suggesting that BFSP was more effective in the reduction of blood alcohol and acetaldehyde. BFSP administration showed the highest induction of hepatic ADH expression in alcohol-feeding rats. Also, alcohol treatment resulted in increasing lipid peroxidative index (thiobarbituric acid-reactive substances) and decreasing antioxidant status (reduced glutathione) in the liver. Thus, these results suggest that BFSP treatment improved the antioxidant status of alcoholic rats by decreasing the levels of lipid peroxidative index and by increasing the levels of antioxidant status in the liver and serum. Specially, the concentrations of serum total cholesterol, free fatty acid and hepatic triglyceride were increased, but these parameters were significantly influenced by the BFSP in the alcohol treatment. Unlike the action of alcohol treatment on fatty liver, BFSP administration attenuated lipid droplet accumulation in hepatocytes. A high level of ADH was also observed in AFSP administered rats; on the other hand, a significant change in ALDH was not observed. Therefore, the SP can be a promising candidate in the prevention alcohol-induced hepatotoxicity and oxidative stress.

Tracing microplastics from raw water to drinking water treatment plants in Busan, South Korea.

The increasing amount of plastic waste has raised concerns about microplastics (MPs) in aquatic environments. MPs can be fragmented into nanoplastics that can pass through water treatment processes and into tap water; potentially threatening human health because of their high adsorption capacity for hazardous organic materials and their intrinsic toxicity. This case study investigates the identification, fate, and removal efficiency of MPs in Korean drinking water treatment plants. Two sites on the Nakdong River, two lake reservoirs (raw water sources), and four corresponding drinking water treatment plants were targeted to trace the amounts, types, and sizes of MPs throughout the treatment process. Monthly quantitative and qualitative analyses were conducted by chemical image mapping using micro-Fourier-transform infrared spectroscopy. MPs larger than 20 µm were detected, and their sizes and types were quantified using siMPle software. Overall, the number of MPs in the river sites (January to April and October to November) exceeded those in the reservoirs, but only slight differences in the number of MPs between rivers and lake reservoirs were detected from June to October. The annual average number of MPs in River A, B and Lack C and D was not distinctively different (2.65, 2.48, 2.46 and 1.87 particles/L, respectively). The majority of MPs found in raw waters were polyethylene (PE)/polypropylene (PP) (> 60%) and polyethylene terephthalate (PET)/poly(methyl methacrylate) (PMMA) (20%), in addition to polyamide (<10%) in the river and polystyrene (<10%) in the lake reservoirs. Approximately 70-80% of the MPs were removed by pre-ozonation/sedimentation; 81-88% of PE/PP was removed by this process. PET/PMMA was removed by filtration. Correlation of MPs with water quality parameters showed that the Mn concentration was moderately correlated with the MP abundance in rivers and lake reservoirs, excluding the lake with the lowest Mn concentration, while the total organic carbon was negatively correlated with the MP abundance in both rivers (A and B) and lake reservoir C.

Flavonoids from silkworm droppings and their promotional activities on heme oxygenase-1.

A new flavane glucoside, 7,2'-dihydroxy-8-hydroxyethyl-4'-methoxyflavane-2'-O-ß-d-glucopyranoside (3), along with three known flavonoids, 7,2'-dihydroxy-8-prenyl-4'-methoxyflavane (1), euchrenone a(7) (2), and 7,2'-dihydroxy-8-prenyl-4'-methoxy-2'-O-ß-d-glucopyranosylflavane (4), was isolated from silkworm droppings. The structures of the compounds were elucidated on the basis of 1D and 2D NMR spectroscopic analyses and optical rotational characteristics. The compounds isolated from silkworm droppings were evaluated for their effects on heme oxygenase-1 (HO-1) activity. Compounds 1 and 3 increased the expression of HO-1 in HepG2 cells. HO-1 is an antioxidant enzyme that catabolizes heme to carbon monoxide, free iron, and biliverdin, all of which are involved in the suppression of inflammatory mediators.

Thirteen-week inhalation toxicity study of 1-propanol in F344 rats.

1-Propanol is a colorless volatile liquid at room temperature and is an important industrial alcohol. Workers are potentially exposed to it through inhalation during industrial activities, including manufacturing, sampling, filling, and mixing processes, as well as during cleaning, maintenance, and repair. Consequently, further information and/or testing for inhalation-related toxicological data is required to assess occupational risk. In this study, 80 (40 male and 40 female) F344 rats were exposed to 1-propanol vapors for 13 weeks (6 h a day, 5 days per week) at target concentrations of 0, 500, 1,600, and 5200 ppm in a whole-body inhalation chamber system. Clinical signs, mean body weight changes, food consumption, hematology, blood biochemistry, necropsy, organ weight, and histopathological findings were observed. The exposure concentrations in chambers were 501.30 ± 9.54 ppm, 1605.43 ± 66.55 ppm, and 5202.19 ± 102.74 ppm for the low, middle, and high dose groups, respectively. No changes related to 1-propanol were observed, including histopathological findings, except for mean body weight changes. The significant decrease in mean body weight at a high dose was not considered to be an adverse effect. Based on these results, the no observed adverse effect concentration of 1-propanol was estimated to be 5202.19 ppm.

Subchronic oral toxicity of silver nanoparticles.

BACKGROUND: The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. RESULTS: This study tested the oral toxicity of silver nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following Organization for Economic Cooperation and Development (OECD) test guideline 408 and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure, although there were no significant changes in food or water consumption during the study period. Significant dose-dependent changes were found in alkaline phosphatase and cholesterol for the male and female rats, indicating that exposure to more than 125 mg/kg of silver nanoparticles may result in slight liver damage. Histopathologic examination revealed a higher incidence of bile-duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in treated animals. There was also a dose-dependent accumulation of silver in all tissues examined. A gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in female kidneys compared to male kidneys. CONCLUSIONS: The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of 125 mg/kg are suggested from the present study.

Histochemical study of intestinal mucins after administration of silver nanoparticles in Sprague-Dawley rats.

To investigate the effects of silver nanoparticles on the histological structure and properties of the mucosubstances in the intestinal mucosa, Sprague-Dawley rats were divided into four groups (10 rats in each group): vehicle control, low-dose group (30 mg/kg), middle-dose group (300 mg/kg), and high-dose group (1,000 mg/kg), and administered silver nanoparticles (60 nm) for 28 days, following OECD test guideline 407 and using GLP. The control sections contained no silver nanoparticles; however, the treated samples showed luminal and surface particles and the tissue also contained silver nanoparticles. A dose-dependent increased accumulation of silver nanoparticles was observed in the lamina propria in both the small and large intestine, and also in the tip of the upper villi in the ileum and protruding surface of the fold in the colon. The silver nanoparticle-treated rats exhibited higher numbers of goblet cells that had released their mucus granules than the controls, resulting in more mucus materials in the crypt lumen and ileal lumen. Moreover, cell shedding at the tip of the villi was frequent. Lower amounts of neutral and acidic mucins were found in the goblet cells in the silver nanoparticle-treated rats, plus the amount of sialomucins was increased, while the amount of sulfomucins was decreased. In particular, in the colon of the silver nanoparticle-treated rats, sialyated mucins were detected in the lamina propria, the connective tissue under the epithelia. Therefore, the present results suggest that silver nanoparticles induce the discharge of mucus granules and an abnormal mucus composition in the goblet cells in the intestines.

Validation of a Korean version of the Moral Sensitivity Questionnaire.

The main purpose of this study was to validate a scale to examine the moral sensitivity of Korean nurses. A pre-existing scale, the Moral Sensitivity Questionnaire (MSQ), developed by Lützén, was used after deletion of three items. The reliability and validity of the scale were examined by using Cronbach's alpha and factor analysis, respectively. According to the results, reliability of the scale was adequate but its construct validity was not fully supported. Through discussion on evidence of validity, five subconstructs emerged. In particular, unlike the factor structure of the MSQ, two subconstructs, patient-oriented care and professional responsibility, were newly extracted. It was assumed that the other three MSQ subconstructs, conflict, meaning and benevolence (expressed as nurses being ethically good), would not be sensitive to cultural background. Given these findings, interpretations about the meaning of moral sensitivity of Korean nurses are discussed.