[Show abstract][Hide abstract] ABSTRACT: We sought to establish a novel method to generate nano-sized carbon black particles (nano-CBPs) with an average size smaller than 100 nm for examining the inhalation exposure risks of experimental rats. We also tested the effect of nano-CBPs on the pulmonary and circulatory systems.
We used chemical vapor deposition (CVD) without the addition of any additives to generate nano-CBPs with a particle size (electrical mobility diameter) of less than 100nm to examine the effects of inhalation exposure. Nano-CBPs were applied to a nose-only inhalation chamber system for studying the inhalation toxicity in rats. The effect on the lungs and circulatory system was determined according to the degree of inflammation as quantified by bronchoalveolar lavage fluid (BALF). The functional alteration of the hemostatic and vasomotor activities was measured by plasma coagulation, platelet activity, contraction and relaxation of blood vessels.
Nano-CBPs were generated in the range of 83.3-87.9 nm. Rats were exposed for 4 hour/day, 5 days/week for 4 weeks to 4.2 × 10(6), 6.2 × 10(5), and 1.3 × 10(5) particles/cm(3). Exposure of nano-CBPs by inhalation resulted in minimal pulmonary inflammation and did not appear to damage the lung tissue. In addition, there was no significant effect on blood functions, such as plasma coagulation and platelet aggregation, or on vasomotor function.
We successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum concentration of 4.2 × 10(6) particles/cm(3) in a nose-only inhalation chamber system. This reliable method can be useful to investigate the biological and toxicological effects of inhalation exposure to nano-CBPs on experimental rats.
[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: We investigated the genotoxicity of two chemicals, methyl formate and 2-methylbutane, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these two chemicals have already been tested numerous times, a micronucleus test has not been conducted and the amounts used have recently been increased.
7 week male ICR mice were tested at dosages of 250, 500, and 1,000 mg/kg for methyl formate and 500, 1,000, and 2,000 mg/kg for 2-methlybutane, respectively. After 24 hours of oral administration with the two 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 two chemicals.
It was concluded that the two 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 two chemicals have no mutagenic potential under each study condition.
[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: Although manganese (Mn) has been shown to increase prolactin (PRL) by decreasing dopamine (DA) in the hypothalamus, the mechanism of Mn-induced regulation of the hypothalamic-hypophyseal-pituitary axis is unclear. We assessed the effects of inhaled Mn on hypothalamic DA and pituitary PRL production and evaluated the role of pituitary-specific transacting factor 1 (Pit-1), a transacting factor of PRL gene, in Mn-induced changes in PRL secretion in the rat brain. Male rats exposed to Mn for 4 or 13 weeks (1.5 mg/m3, 6 h/day, 5 days/week) showed a progressive and significant decrease in hypothalamic DA, whereas PRL and Pit-1 mRNA levels increased in response to Mn exposure. These results suggest that exposure to Mn decreases hypothalamic DA and promotes the production of PRL in the pituitary and that Pit-1 might be a regulator of DA and PRL.
[Show abstract][Hide abstract] ABSTRACT: Carbon black is classified as carcinogen group 2B by International Agency for Research on Cancer (IARC). But it uncertained the effects of ultrafine carbon black particles on oxidative damage or inflammation. So we were focused to evaluate the oxidative damage or inflammation with ultrafine carbon black particles at gene expression level by using mouse macrophage cell line, and the co-effects with solvent coating to it. It was evaluated the changes of gene expression with real time RT-PCR, and oxidative DNA damage with Fragment Length Analysis with Restriction Enzyme (FLARE) assay in mouse macrophage (RAW264.7) cell line. Two kinds of carbon black induced the gene expression of cytokines related to acute inflammation, and with 0.1% methylcyclohexane coating were regulated conversely each other. The oxidative DNA damage with smaller size carbon black was increased than bigger one (the range with 500–30 nm). The 0.1% methylcyclohexane increased the damage by binding with each carbon black (the dose range with 100 ng/mL-100 μg/mL). In this study, we got the conclusion that the genotoxicity of carbon blacks are elevated with its size get smaller and their surface area wider, and with methylcyclohexane coating. It could cause DNA damage by promoting oxidative stress and inflammatory responses.
Molecular and Cellular Toxicology 7(4). · 0.83 Impact Factor