Histopathological changes in the lungs of rats instilled with Korean chrysotile.

To evaluate the pulmonary toxicity of Korean chrysotile (KC), 1 or 2 mg of KC (low- and high-concentration groups, respectively) was instilled in the lungs of Sprague-Dawley rats by a single intratracheal instillation. The lungs were examined using a light microscope at several time points (5 days, 5 weeks, and 10 weeks). Up to 10 weeks after KC instillation, differences were observed in the pathological reactions and ultimately in lung recovery between the two groups. At 5 days after KC instillation, lung weight increased and severe bronchiolitis obliterans developed in proportion to the KC concentration administered. From 5 to 10 weeks after KC administration, the lung weight of the low-concentration group increased and bronchiolitis obliterans worsened. In the high-concentration group, the lung weight and the severity of bronchiolitis obliterans at 10 weeks after administration of KC declined compared to those at 5 weeks. In conclusion, the effects of KC on lung tissue were initially found to be more influenced by the amount of fiber, but over time, the effects were influenced by the residual fibrous material in the lung tissue and its biodurability.

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

1-Propanol is used as a solvent for waxes, vegetable oils, resins, cellulose esters, and ethers, and is not considered harmful to humans by food and non-occupational exposures. However, workers are potentially exposed to 1-propanol by inhalation when it is used in the workplace. Thus, inhalation toxicity data are needed to assess the hazard of 1-propanol for workers safety. Five male and five female F344 rats were exposed to 1-propanol vapor for 4-weeks (6 h/day, 5 days/week) at concentrations of 0, 100, 400, and 1600 ppm in a whole-body inhalation chamber system. The actual exposure concentrations were 100.11 ± 5.10, 403.19 ± 12.31, and 1598.08 ± 139.58 ppm for the low, middle, and high dose groups, respectively. No clinical signs, significant mean body weight changes, significant changes of hematology or blood biochemistry results, or histopathological abnormalities were seen related to exposure to the test substance. Under the conditions of this study, the no-observed-adverse-effect level of 1-propanol was over 1600 ppm.

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

1-Methylnaphthalene is generally utilized in solvents, as an intermediate in organic synthesis, a dye carrier, in resins, and others. There are some toxicological studies of 1-methylnaphthalene; however, inhalation toxicity studies are rare. Each of 10 male and female F344 rats was exposed to vapors of 1-methylnaphthalene for 13 weeks (6 h a day, 5 days per week) at concentrations of 0, 0.5, 4, and 30 ppm in a whole-body inhalation chamber system. The exposure concentrations were 0.52 ± 0.05, 4.08 ± 0.25, and 30.83 ± 1.28 ppm for the low-, middle-, and high-dose group, respectively. Body weight changes were not affected by exposure to 1-methylnaphthalene. Blood prothrombin time was delayed at 30 ppm in male and female groups, and activated partial thromboplastin time was also delayed at 30 ppm in the male group. Values of alanine aminotransferase in the serum were decreased and those of albumin were increased at 30 ppm in the male group. Differential cell counts and levels of lactate dehydrogenase in the bronchoalveolar lavage fluid were not affected. However, mucous cell hyperplasia in the nasopharyngeal tissues was found and the severity was correlated to exposure concentrations. In conclusion, 1-methylnaphthalene mainly affects the upper respiratory system and the no-observed-adverse-effect level is suggested to be 4 ppm on the basis of histopathological findings.

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.

Twenty-Eight-Day Repeated Inhalation Toxicity Study of Aluminum Oxide Nanoparticles in Male Sprague-Dawley Rats.

Aluminum oxide nanoparticles (Al2O3 NPs) are among the most widely used nanomaterials; however, relatively little information about their risk identification and assessment is available. In the present study, we aimed to investigate the potential toxicity of Al2O3 NPs following repeated inhalation exposure in male Sprague-Dawley rats. Rats were exposed to Al2O3 NPs for 28 days (5 days/week) at doses of 0, 0.2, 1, and 5 mg/m3 using a nose-only inhalation system. During the experimental period, we evaluated the clinical signs, body weight change, hematological and serum biochemical parameters, necropsy findings, organ weight, and histopathology findings. Additionally, we analyzed the bronchoalveolar lavage fluid (BALF), including differential leukocyte counts, and aluminum contents in the major organs and blood. Aluminum contents were the highest in lung tissues and showed a dose-dependent relationship in the exposure group. Histopathology showed alveolar macrophage accumulation in the lungs of rats in the 5 mg/m3 group during exposure and recovery. These changes tended to increase at the end of the recovery period. In the BALF analysis, total cell and neutrophil counts and lactate dehydrogenase, tumor necrosis factor-α, and interleukin-6 levels significantly increased in the 1 and 5 mg/m3 groups during exposure. Under the present experimental conditions, we suggested that the no-observed-adverse-effect level of Al2O3 NPs in male rats was 1 mg/m3, and the target organ was the lung.

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.

Oxidative stress and sex difference in liver of rats exposed to cyclohexanone / Estrés oxidativo y diferencia sexual en el hígado de ratas expuestas a ciclohexanona

Cyclohexanone is widely used in industry for the organic synthesis of chemicals such as adipic acid, caprolactam, polyvinyl chloride and its copolymers, and methacrylate ester polymers. Its mechanism of toxicity, especially oxidative stress, is rarely reported in cyclohexanone toxicity studies. In this study, we evaluate oxidative stress immunohistochemically in the livers of rats exposed to cyclohexanone. Rats were exposed to 0 ppm and 625 ppm cyclohexanone for 6 h/day, 5 days/week, for 13 weeks via whole-body inhalation. All rats were sacrificed at the end of exposure and livers were removed and prepared for histological examination. Histopathology indicated an increase in bile duct hyperplasia in the liver was only observed in the cyclohexanone-exposed group, compared to that in the control group in males. Immunohistochemistry showed 4-HNE immunoreactivity in the cytoplasm of hepatocytes in the liver. Immunoreactivity was significantly stronger in the cyclohexanone-exposed group compared to the control group in both sexes. However, it was significantly stronger in males compared to females. This result shows a sex-based difference in the expression of oxidative stress in response to cyclohexanone exposure.

La ciclohexanona se usa ampliamente en la industria para la síntesis orgánica de sustancias químicas, como el ácido adípico, la caprolactama, el cloruro de polivinilo y sus copolímeros y los polímeros del éster metacrilato. Su mecanismo de toxicidad, especialmente el estrés oxidativo, se observa raramente en los estudios de toxicidad de la ciclohexanona. En el presente estudio, evaluamos el estrés oxidativo a través de la inmunohistoquímica en hígados de ratas expuestas a la ciclohexanona. Las ratas fueron expuestas a 0 ppm y 625 ppm de ciclohexanona por 6 horas diarias, 5 días a la semana durante 13 semanas, mediante inhalación corporal total. Al final de la exposición, se sacrificaron las ratas y se extirparon sus hígados para el examen histológico. La histopatología indicó que se observó un aumento de la hiperplasia del conducto biliar solamente en el grupo expuesto a la ciclohexanona, en comparación con el grupo de control en machos. La inmunohistoquímica mostró una inmunorreactividad al 4-HNE en el citoplasma de los hepatocitos del hígado. La inmunorreactividad fue significativamente mayor en el grupo expuesto a la ciclohexanona, en comparación con el grupo control en ambos sexos. Sin embargo, fue significativamente mayor en los machos, en comparación con el hígado de las hembras. Este resultado muestra una diferencia basada en el sexo, en la expresión del estrés oxidativo en respuesta a la exposición a la ciclohexanona.

Twenty-Eight-Day Repeated Inhalation Toxicity Study of Nano-Sized Neodymium Oxide in Male Sprague-Dawley Rats.

Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide (Nd2O3) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized Nd2O3-containing aerosols via a nose-only inhalation system at doses of 0 mg/m3, 0.5 mg/m3, 2.5 mg/m3, and 10 mg/m3 for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the 2.5 mg/m3 and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the 0.5 mg/m3 treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the 0.5 mg/m3 group, but were exacerbated in the 10 mg/m3 group. The lowest-observed-adverse-effect concentration of nano-sized Nd2O3 was determined to be 0.5 mg/m3, and the target organ was determined to be the lung, under the present experimental conditions in male rats.

Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure.

Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were 0.63 µm, 0.81 µm, and 1.65 µm, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low (0.11 ± 0.06 mg/m3), the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high (1.41 ± 0.71 mg/m3) male group and 15% lower in the high (1.41 ± 0.71 mg/m3) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is 0.11 mg/m3.

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.

Toxicity of Two Different Sized Lanthanum Oxides in Cultured Cells and Sprague-Dawley Rats.

In recent years, the use of both nano- and micro-sized lanthanum has been increasing in the production of optical glasses, batteries, alloys, etc. However, a hazard assessment has not been performed to determine the degree of toxicity of lanthanum. Therefore, the purpose of this study was to identify the toxicity of both nano- and micro-sized lanthanum oxide in cultured cells and rats. After identifying the size and the morphology of lanthanum oxides, the toxicity of two different sized lanthanum oxides was compared in cultured RAW264.7 cells and A549 cells. The toxicity of the lanthanum oxides was also analyzed using rats. The half maximal inhibitory concentrations of micro-La2O3 in the RAW264.7 cells, with and without sonication, were 17.3 and 12.7 times higher than those of nano-La2O3, respectively. Similar to the RAW264.7 cells, the toxicity of nano-La2O3 was stronger than that of micro-La2O3 in the A549 cells. We found that nano-La2O3 was absorbed in the lungs more and was eliminated more slowly than micro-La2O3. At a dosage that did not affect the body weight, numbers of leukocytes, and concentrations of lactate dehydrogenase and albumin in the bronchoalveolar lavage (BAL) fluids, the weight of the lungs increased. Inflammatory effects on BAL decreased over time, but lung weight increased and the proteinosis of the lung became severe over time. The effects of particle size on the toxicity of lanthanum oxides in rats were less than in the cultured cells. In conclusion, smaller lanthanum oxides were more toxic in the cultured cells, and sonication decreased their size and increased their toxicity. The smaller-sized lanthanum was absorbed more into the lungs and caused more toxicity in the lungs. The histopathological symptoms caused by lanthanum oxide in the lungs did not go away and continued to worsen until 13 weeks after the initial exposure.

Exposure monitoring and risk assessment of biphenyl in the workplace.

This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier and polish in industry. Vapor or high levels of dust inhalation and dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory organs, and permanent lesions in the liver and nervous system. In this study, the workplace environment concentrations were assessed as central tendency exposure and reasonable maximum exposure and were shown to be 0.03 and 0.12 mg/m³, respectively. In addition, the carcinogenic risk of biphenyl as determined by risk assessment was 0.14 × 10⁻4 (central tendency exposure) and 0.56 × 10⁻4 (reasonable maximum exposure), which is below the acceptable risk value of 1.0 × 10⁻4. Furthermore, the central tendency exposure and reasonable maximum exposure hazard quotients were 0.01 and 0.06 for oral toxicity, 0.05 and 0.23 for inhalation toxicity, and 0.08 and 0.39 for reproduction toxicity, respectively, which are all lower than the acceptable hazard quotient of 1.0. Therefore, exposure to biphenyl was found to be safe in current workplace environments. Because occupational exposure limits are based on socioeconomic assessment, they are generally higher than true values seen in toxicity experiments. Based on the results of exposure monitoring of biphenyl, the current occupational exposure limits in Korea could be reviewed.

Effects of didecyldimethylammonium chloride on sprague-dawley rats after two weeks of inhalation exposure.

Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately 0.15 mg/m(3), 0.6 mg/m(3), and 3.6 mg/m(3) DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was 1.86 µm and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were 0.15 ± 0.15 mg/m(3), 0.58 ± 0.40 mg/m(3), and 3.63 ± 1.56 mg/m(3), respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The noobserved-adverse-effect level (NOAEL) for DDAC was determined as 0.15 mg/m(3).

Biologically hazardous agents at work and efforts to protect workers' health: a review of recent reports.

Because information on biological agents in the workplace is lacking, biological hazard analyses at the workplace to securely recognize the harmful factors with biological basis are desperately needed. This review concentrates on literatures published after 2010 that attempted to detect biological hazards to humans, especially workers, and the efforts to protect them against these factors. It is important to improve the current understanding of the health hazards caused by biological factors at the workplace. In addition, this review briefly describes these factors and provides some examples of their adverse health effects. It also reviews risk assessments, protection with personal protective equipment, prevention with training of workers, regulations, as well as vaccinations.

Studies on the toxicity and distribution of indium compounds according to particle size in sprague-dawley rats.

OBJECTIVES: The use of indium compounds, especially those of small size, for the production of semiconductors, liquid-crystal panels, etc., has increased recently. However, the role of particle size or the chemical composition of indium compounds in their toxicity and distribution in the body has not been sufficiently investigated. Therefore, the aim of this study was to examine the effects of particle size and the chemical composition of indium compounds on their toxicity and distribution. METHODS: Male Sprague-Dawley rats were exposed to two different-sized indium oxides (average particle sizes under 4,000 nm [IO_4000] and 100 nm [IO_100]) and one nano-sized indium-tin oxide (ITO; average particle size less than 50 nm) by inhalation for 6 hr daily, 5 days per week, for 4 weeks at approximately 1 mg/m(3) of indium by mass concentration. RESULTS: We observed differences in lung weights and histopathological findings, differential cell counts, and cell damage indicators in the bronchoalveolar lavage fluid between the normal control group and IO- or ITO-exposed groups. However, only ITO affected respiratory functions in exposed rats. Overall, the toxicity of ITO was much higher than that of IOs; the toxicity of IO_4000 was higher than that of IO_100. A 4-week recovery period was not sufficient to alleviate the toxic effects of IO and ITO exposure. Inhaled indium was mainly deposited in the lungs. ITO in the lungs was removed more slowly than IOs; IO_4000 was removed faster than IO_100. IOs were not distributed to other organs (i.e., the brain, liver, and spleen), whereas ITO was. Concentrations of indium in the blood and organ tissues were higher at 4 weeks after exposure. CONCLUSIONS: The effect of particle size on the toxicity of indium compounds was not clear, whereas chemical composition clearly affected toxicity; ITO showed much higher toxicity than that of IO.

Effects of Nano-sized Carbon Black on the Lungs of High Fat-diet Induced Overweight Rats.

OBJECTIVES: This study was conducted to determine whether nano-sized carbon black exposure results in greater damage in high fat diet-induced overweight rats than normal weight ones and to identify the possible causes of any differences. METHODS: Two groups of Sprague-Dawley rats allocated by body weight (normal and overweight) were exposed to aerosolized nano-sized carbon black for 6 hours a day, 5 days per week over a 4-week period. Differential cell counts, lactate dehydrogenase (LDH) activities and albumin concentrations were measured in bronchoalveolar lavage (BAL) fluid, and histopathological findings in the lungs were evaluated. Tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 were measured in BAL fluid and supernatants of lipopolysaccharide(LPS)-stimulated lymphocyte culture. RESULTS: Rats exposed to high concentrations of nano-sized carbon black showed significantly increased (p<0.05) polymorphonuclear leukocyte number and LDH activity in the BAL fluid from both overweight and normal rats. Mild histopathological changes were observed in normal rats irrespective of carbon black concentrations. However, severe histological scores were found in overweight rats (1.75±0.46, 2.25±0.46, and 2.88±0.35 after low, medium, and high concentration exposures). Proinflammatory cytokine levels of TNF-α and IL-6 were significantly higher in the supernatant of LPS-stimulated lymphocytes of overweight rats, whereas there was no significant difference in the BAL fluid between normal and overweight rats. CONCLUSIONS: Inflammation and damage to lungs exposed to nano-sized carbon black was more severe in high fat diet-induced overweight rats compared to normal rats.

Comparison of toxicity and deposition of nano-sized carbon black aerosol prepared with or without dispersing sonication.

Nanotoxicological research has shown toxicity of nanomaterials to be inversely related to particle size. However, the contribution of agglomeration to the toxicity of nanomaterials has not been sufficiently studied, although it is known that agglomeration is associated with increased nanomaterial size. In this study, we prepared aerosols of nano-sized carbon black by 2 different ways to verify the effects of agglomeration on the toxicity and deposition of nano-sized carbon black. The 2 methods of preparation included the carbon black dispersion method that facilitated clustering without sonication and the carbon black dispersion method involving sonication to achieve scattering and deagglomeration. Male Sprague-Dawley rats were exposed to carbon black aerosols 6 hr a day for 3 days or for 2 weeks. The median mass aerodynamic diameter of carbon black aerosols averaged 2.08 µm (for aerosol prepared without sonication; group N) and 1.79 µm (for aerosol prepared without sonication; group S). The average concentration of carbon black during the exposure period for group N and group S was 13.08 ± 3.18 mg/m(3) and 13.67 ± 3.54 mg/ m(3), respectively, in the 3-day experiment. The average concentration during the 2-week experiment was 9.83 ± 3.42 mg/m(3) and 9.08 ± 4.49 mg/m(3) for group N and group S, respectively. The amount of carbon black deposition in the lungs was significantly higher in group S than in group N in both 3-day and 2-week experiments. The number of total cells, macrophages and polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) fluid, and the number of total white blood cells and neutrophils in the blood in the 2- week experiment were significantly higher in group S than in normal control. However, differences were not found in the inflammatory cytokine levels (IL-1ß, TNF-α, IL-6, etc.) and protein indicators of cell damage (albumin and lactate dehydrogenase) in the BAL fluid of both group N and group S as compared to the normal control. In conclusion, carbon black aerosol generated by sonication possesses smaller nanoparticles that are deposited to a greater extent in the lungs than is aerosol formulated without sonication. Additionally, rats were narrowly more affected when exposed to carbon black aerosol generated by sonication as compared to that produced without sonication.

The impact of intratracheally instilled carbon black on the cardiovascular system of rats: elevation of blood homocysteine and hyperactivity of platelets.

Carbon black (CB) is an industrial chemical with high potential for human exposure. Although the relationship between exposure to particulate matter (PM) and cardiovascular disease is well documented, the risk of adverse cardiovascular effects attributed to CB particles has not been clearly characterized. This study was performed to (1) investigate the effects of CB on cardiovascular system and (2) identify the target tissue or potential biomarkers. Carbon black with a distinct particle size, N330 (ultrafine particle) and N990 (fine particle), was intratracheally instilled into rats at a doses of 1, 3, or 10 mg/kg. Measurements of thrombotic activity and determination of plasma homocysteine levels, cardiac functionality, and inflammatory responses were conducted at 24-h and 1-wk time points. Exposure to N330 accelerated platelet-dependent blood clotting at 10 mg/kg, the highest exposure tested. Unexpectedly, both N330 and N990 led to prolongation of activated partial thromboplastin time (aPTT), whereas these CB particles failed to affect prothrombin time (PT). N990 produced a significant elevation in the level of plasma homocysteine, a well-established etiological factor in cardiovascular diseases. Both N330 and N990 induced apparent inflammation in the lungs; however, both particles failed to initiate systemic inflammation. Neither CB particle produced observable cardiac symptoms as detected by electrocardiography. Taken together, data show CB exposure enhanced the cardiovascular risk by inducing hyperhomocysteinemia and platelet hyperactivity, although these effects may be variable depending on particle size and exposure duration. Homocysteine may be a potential biomarker for cardiovascular toxicity following CB exposure.

Effect of Agglomeration on the Toxicity of Nano-sized Carbon Black in Sprague-Dawley Rats.

OBJECTIVES: Recent studies have shown that nano-sized carbon black is more toxic than large respirable carbon black because of its higher surface area. However, it is not clear if carbon black made larger by agglomeration demonstrates decreased toxicity. The purpose of this study was to verify if agglomeration affects the toxicity of carbon black using three differently prepared nano-sized carbon black aerosols in nose-only inhalation chambers for 13 weeks. METHODS: Printex 90 was selected as a representative nano-sized carbon black. To generate aerosols of three different types of agglomerates, Printex 90 was dispersed in distilled water by three different methods: vortex, vortex+sonication, and vortex+sonication with dispersion in a stabilizer. Then, the three differently prepared solutions were aerosolized through venturi nozzles. Male Sprague-Dawley rats were exposed to Printex 90 aerosols in a nose-only exposure chamber for 6 h/d, 5 d/wk for 13 weeks at a concentration of approximately 9 mg/m(3). RESULTS: Numbers of total cells in the bronchoalveolar lavage (BAL) fluid, macrophages, and polymorphonuclear leukocytes were increased and carbon black masses were clearly seen in BAL cells and lung tissues of rats exposed to Printex 90. However, few differences were found between the three differently agglomerated aerosols. In addition, there were no significant differences in other parameters, such as body weight, lung function or cytokine levels in BAL fluid following carbon black exposure. CONCLUSIONS: Only mild to moderate respiratory effects were found in rats exposed to nano-sized carbon black at 9 mg/m(3) for 13 weeks. Agglomeration did not affect the toxicity of nano-sized carbon particles.