[Show abstract][Hide abstract] ABSTRACT: The use of nanoparticles (NPs) in industry is increasing, bringing with it a number of adverse health effects on workers. Like other chemical carcinogens, NPs can cause cancer via oxidative DNA damage. Of all the molecules vulnerable to oxidative modification by NPs, DNA has received the greatest attention, and biomarkers of exposure and effect are nearing validation. This review concentrates on studies published between 2000 and 2012 that attempted to detect oxidative DNA damage in humans, laboratory animals, and cell lines. It is important to review these studies to improve the current understanding of the oxidative DNA damage caused by NP exposure in the workplace. In addition to examining studies on oxidative damage, this review briefly describes NPs, giving some examples of their adverse effects, and reviews occupational exposure assessments and approaches to minimizing exposure (e.g., personal protective equipment and engineering controls such as fume hoods). Current recommendations to minimize exposure are largely based on common sense, analogy to ultrafine material toxicity, and general health and safety recommendations.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to verify subchronic inhalation toxicity of methylcyclopentane (CAS No. 96-37-7) in Sprague-Dawley rats. Four groups of 10 rats of each gender were exposed to methylcyclopentane vapor by whole-body inhalation at concentrations of 0, 290, 1300, or 5870 ppm for 6 h per day, 5 days/week over a 13-week period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. Exposure-related clinical signs (salivation and rubbing) were observed in both genders of the 5870 ppm group. There was an increase in liver weight for both genders but the kidney weight was only higher in females than controls. However, no toxicologically significant changes were observed in body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings, or histopathology in any of the treatment groups. Under the present experimental conditions, the target organs were determined to be kidney and liver in rats. The no-observed-adverse-effect concentration was considered to be 1300 ppm/6 h/day in rats.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2013; · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To classify the chemical hazard according to globally harmonized system of classification and labeling of chemicals (GHS), we investigated the genotoxicity of three chemicals, methyl myristate, 2-ethylhexanoic acid zinc salt, N,N,N',N'-tetrakis(2-hydroxyethyl) ethylenediamine, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these three chemicals have already been tested numerous times, a micronucleus test has not been conducted. The seven week-old male ICR mice were tested at three dosages for the three chemicals, respectively. After 24 h of oral administration with the three chemicals, the mice were sacrificed and their bone marrow cells were prepared for smearing slides. As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes, all treated groups expressed no statistically significant increase of MNPCE compared to the negative control group. There were no clinical signs related with the oral exposure of these three chemicals. It was concluded that these three chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and there was no direct proportion with dosage. These results indicate that the three chemicals have no mutagenic potential under each test condition, and it is not classified these chemicals as mutagens by GHS.
Journal of Applied Biological Chemistry 01/2013; 56(4).
[Show abstract][Hide abstract] ABSTRACT: There is limited data regarding the toxicity of methylcyclohexane, despite its wide use in rubber adhesives, paint diluents, and cleansing agents. This study aimed to verify the toxicity and influence on the reproductive system of methylcyclohexane after its repeated injection in Sprague Dawley (SD) rats.
Methylcyclohexane was injected subcutaneously into male and female SD rats once a day, five times a week, for 13 weeks at different doses (0, 10, 100, and 1,000 mg/kg/day) for each group. The toxicity of testing material was verified by observing the change in body and organ weight, hematological change, pathological findings, and effect on the reproductive system at each different concentration.
In the 1,000 mg/kg/day group, there were cases of animal deaths. In animals that survived, hematological changes, including a decrease in the red blood cell count, were observed. A considerable weight gain or loss and pathological abnormalities in the liver, kidney, and other organs were found. However, the 10 and 100 mg/kg/day groups did not cause deaths or other specific abnormalities. In terms of reproductive toxicity, there were changes in hormone levels, including a significant decrease in hormones such as estradiol and progesterone (p < 0.001) in male animals. Menstrual cycle change for female animals did not show concentration dependency.
When injected repeatedly for 13 weeks, methylcyclohexane proved to be toxic for the liver, heart, and kidney at a high dose. The absolute toxic dose was 1,000 mg/kg/day, while the no observed adverse effect level was less than 100 mg/kg/day. The substance exerted little influence on the reproductive system.
[Show abstract][Hide abstract] ABSTRACT: In this study, the in vitro mammalian chromosomal aberration (CA) assay was conducted to gain additional information concerning the hazards associated with the use of cyclopentane and ammonium nitrate. While these two chemicals had already been tested by many methods, they had not been studied in the CA test.
The assay was performed using the ovarian infantile cell (CHO-K1 cell), by the direct method (-S9) and by the metabolic activated method (+S9 mix).
Using the direct method, the 7 dosages in a 48 hour treatment group did not show that the frequency of CA is proportion to the dosage addition. The frequency of CA is not proportion to the dosage addition for a 6 hour treatment using the metabolic activated method.
From these findings, it was decided that the 2 chemicals do not induce chromosomal aberrations under the tested conditions.
[Show abstract][Hide abstract] ABSTRACT: We investigated the genotoxicities or mutagenicities of 2 chemicals (octane and tetrasodium pyrophosphate) with limited toxicological data in spite of their common usage based on Ames reverse mutation test. In this test, treatment of 2 chemicals at each five dose did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and in Escherichia coli WP2uvrA with and without metabolic activation. These results indicate that 2 chemicals do not have mutagenic potentials under the conditions examined in each study. Despite these results, it can affect by inducing inhalation, skin or eye contact, ingestion, and have affected central nervous system as a target organ. It is thus necessary to prepare the local exhaust system and personal protective equipments. Based on this study, we suggest that future studies should be directed toward chronic inhalation, carcinogenic test and so on.
The Journal of Toxicological Sciences 08/2010; 35(4):555-62. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The subchronic toxicity of sec-butanethiol was investigated in Sprague-Dawley rats following a 13-week period of repeated inhalation exposure. Four groups of 10 rats of each sex were exposed to sec-butanethiol vapor by whole-body inhalation at 0, 25, 100, or 400 ppm for 6 h per day, 5 days a week over a 13-week period. At 400 ppm, both genders exhibited a decrease in food consumption, although a decrease in the body weight gain was only observed in females. Hematological investigations revealed a decrease in red blood cell, hemoglobin, and hematocrit in both the male and female groups, whilst the female group exhibited an increase in the mean corpuscular volume and a decrease in the mean corpuscular hemoglobin concentration. There was an increase in kidney weight for both genders but the liver weight was only higher in males than controls. Histopathological alterations were found in the kidneys, spleen, and nasal olfactory epithelium. There were no treatment-related effects observed in both genders at 100 ppm. Under the present experimental conditions, the target organs were determined to be the blood cells, the kidneys, the liver, and the nasal turbinates in rats. The no-observed-effect level was considered to be 100 ppm in rats.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 07/2009; 47(9):2294-301. · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuronal accumulation of 1-methyl-4-phenylpyridinium ion (MPP(+)), the metabolite of neural toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP), induces a rapid depletion of cellular ATP level and loss of neuronal cell viability which simulates human Parkinson's disease (PD). Since ATP plays an important role in the physiology and function of platelets, which share many biochemical and physiological features with neuronal cells, we examined the effect of MPP(+) on platelet aggregation and viability using freshly isolated rat platelets. While the treatment of MPP(+) to platelets did not induce cytotoxicity, it significantly attenuated agonist-induced platelet aggregation in a concentration dependent manner. The inhibition of aggregation by MPP(+) was mediated by the depletion of the cytoplasmic ATP pool and resultant decreased ATP secretion. Different from the previous reports in neuronal cells, MPP(+) did not affect intracellular levels of glutathione and cytoplasmic Ca(2+) in platelets. The combined treatment with MPP(+) and 2-deoxyglucose, a glycolysis inhibitor, showed the additive effect in the decrease of ATP secretion and intracellular content. Consistent with these findings, inhibitory effects of MPP(+) on platelet aggregation was significantly enhanced by the treatment with 2-deoxyglucose. In conclusion, these results suggested that MPP(+) can induce ATP depletion in platelets and attenuate platelet aggregation providing a new theory on the reduced platelet activities in PD patients.
[Show abstract][Hide abstract] ABSTRACT: The subchronic toxicity of 1,3-dichloro-2-propanol (1,3-DCP) was investigated in Fischer 344 rats after 13 weeks of repeated, whole-body inhalation exposure. Groups of 10 rats of each sex were exposed to 1,3-DCP vapor by whole-body inhalation exposure at concentrations of 0, 5, 20 or 80 ppm for 6 h/day, 5 days/week for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were assessed. At 80 ppm, a decrease in the body weight gain, an increase in the urine protein and leukocyte counts and an increase in the liver and kidney weights were observed in both genders. Hematological and serum biochemical investigations revealed decreases in hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular HB, as well as increases in the platelet (PLT) count, serum aspartate aminotransferase and alanine aminotransferase. The number of white blood cells was significantly lower in males than in controls, but this was not the case in females. Histopathological alterations included an increase in the incidence of multifocal necrosis, inflammation, pigmentation, biliary hyperplasia and the foci of cellular alteration of the liver and chronic nephropathy and protein cast of the kidney. At 20 ppm, decreases in HCT and MCV and increases in the liver and kidney weights were observed in both genders. A decrease in the HB of females and an increase in the PLT count of females were also observed. Histopathological alterations included slight increases in the incidences of hepatic necrosis, hepatic inflammation and chronic nephropathy. At 5 ppm, we found decreases in the MCV of males and the HB of females, as well as an increase in the liver weight of both genders. In the present experimental conditions, the target organs were determined to be the liver, kidney and blood cells in rats. The no-observed-adverse-effect level was considered to be <5 ppm/6 h/day and the low-observed-adverse-effect level was believed to be 5 ppm/6 h/day in rats.
Annals of Occupational Hygiene 10/2007; 51(7):633-43. · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We performed a 90-day repeated-dose inhalation toxicity study of soluble hexavalent chromium trioxide (CrO3 (VI)). Male Sprague-Dawley (SD) rats were exposed to doses of CrO3 in the form of 0.5 approximately 5.0 microm aerosol at 0.00, 0.20, 0.50, and 1.25 mg/m3 for 6 h/day, 5 days/week for 13 weeks using inhalation chamber. CrO3 induced decrease of activity, alopecia and nasal hemorrhage. Body weights of the high-dose 1.25-mg/m3 exposure group were significantly lower than those of the control group. Hematological results revealed the reduction of the number of red blood cell and hematocrit values in the 1.25-mg/m3 exposure group. In addition, the hemoglobin values in the 0.50- and 1.25-mg/m3 exposure groups were significantly decreased compared with those of the control group. Clinical biochemical measurements revealed the reduction in total protein, albumin and alanine aminotransferase (ALT) level of the 0.50- and 1.25-mg/m3 exposure groups. Microscopic examination of the lung showed inflammation reactions caused by Cr exposure. In conclusion, the 13-week repeated exposure with soluble CrO3 demonstrated the injury in SD rats with the no observed adverse effect level (NOAEL) under 0.20 mg/m3.
Archive für Toxikologie 08/2004; 78(7):363-8. · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the genotoxic effect of l,1-dichloro-1-fluoroethane (HCFC-141b), which was currently widely used as a cleaning solvent in the electronic parts industry and suggested as a potential reproductive effector, in vivo micronucleus tests were performed. Groups of 10 male and 10 female Sprague-Dawley rats were exposed, by inhalation (6h/day, 5 days/week) to the vapors of HCFC-141b for 13 weeks using whole body exposure chambers at the concentrations of 0 (control), 1500, 3000, and 6000 ppm. The micronuclei frequencies among the polychromatic erythrocytes (PCEs) and the percentage of polychromatic erythrocytes among the total number of erythrocytes were counted in the bone marrow of rats, and body weights, organ weights, histopathology, clinical chemistry and hematologic changes were also observed. Statistically significant and dose-dependant increases were found in the micronuclei frequencies in the male rats (P<0.01), yet not in the females. The decreases in the percentage of polychromatic erythrocytes among the total number of erythrocytes were also statistically significant (P<0.05) in both sexes of the high concentration groups. However, no exposure-related effects of toxicological significance were noted with respect to organ weights, clinical chemistry and histopathology. Apart from it, only slightly decreased mean corpuscular hemoglobin concentration (MCHC) was noted in the females of 6000 ppm group (P<0.05). These results suggest that HCFC 141b can induce the genetic effects, micronuclei in the rat bone marrows, especially in males, at earlier stages before the other general clinical and histopathologic changes occur if with more prolonged exposure.
[Show abstract][Hide abstract] ABSTRACT: According to the toxicological and epidemiological studies, hexavalent chromium (Cr) is associated with increase of lung cancer risk. Genotoxic effects, such as chromosomal aberrations, and cellular oxidative DNA damage by reactive oxygen species produced by hexavalent Cr exposure may play an important role in its carcinogenesis. To clarify whether reactive oxygen species are involved in its mechanism, we examined the levels of 8-hydroxydeoxyguanine (8-OH-dG) and its base excision repair activities in the lung tissues of rats that repeatedly inhaled a sodium chromate solution mist for 1, 2, and 3 weeks. The levels of 8-OH-dG increased significantly in the lung tissues of the rats exposed for 1 week at the low concentration (0.18 mg/m(3), P<0.05), as compared with the controls. However, there was no difference in the 8-OH-dG levels at the higher concentration or with more than 2 weeks of exposure. The 8-OH-dG repair activities decreased in a dose-dependent manner during 2 weeks of exposure, on the contrary they recovered at 3 weeks of repeated exposure. These results suggest that the DNA damage caused by hexavalent Cr inhalation is induced by the generation of reactive oxygen species and by inhibition of base excision repair activity during the earlier phase of exposure. However, the 8-OH-dG levels and its repair activities recovered to the level of the controls in the latter inhalation exposure period.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 08/2003; 539(1-2):109-16. · 3.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 1-Bromopropane (1-BP) has recently become known as an alternative cleaning material with less damage to the ozone layer. However, its toxicity is not fully evaluated. This study was designed to investigate the repeated inhalation toxicity of 1-BP on the nervous systems in Sprague-Dawley rats. The experiment was done by repeated exposure of the rats to 0, 200, 500, and 1250 ppm for 6 h per day, 5 days a week, for 13 weeks, respectively. Morphologic studies were done for the central nervous system, sacral and peroneal nerves. The serial sections of the brain and spinal cord of 1-BP inhalation groups revealed no pathological features either in the gray or white matter. The nerve fiber teasing, light and electron microscopic studies of the sacral and peroneal nerve fibers showed no significant difference between 1-BP inhalation groups and the control group. From these results, it is concluded that the nervous system is histologically resistant to the repeated inhalation of 1-BP up to 1250 ppm for 13 weeks. Experiments with higher concentrations of 1-BP and the functional studies are necessary to clarify the 1-BP toxicity.